Effects of heat-treatment on plasma rich in growth factors-derived autologous eye drop.

PubMed

Anitua, E; Muruzabal, F; De la Fuente, M; Merayo-Lloves, J; Orive, G

2014-02-01

We have developed and characterized a new type of plasma rich in growth factors (PRGF) derived eye-drop therapy for patients suffering from autoimmune diseases. To determine the concentration of several growth factors, proteins, immunoglobulins and complement activity of the heat-inactivated eye-drop and to study its biological effects on cell proliferation and migration of different ocular surface cells, blood from healthy donors was collected, centrifuged and PRGF was prepared avoiding the buffy coat. The half volume of the obtained plasma supernatant from each donor was heat-inactivated at 56 °C for 1 h (heat-inactivated PRGF). The concentration of several proteins involved on corneal wound healing, immunoglubolins G, M and E and functional integrity of the complement system assayed by CH50 test were determined. The proliferative and migratory potential of inactivated and non-inactivated PRGF eye drops were assayed on corneal epithelial cells (HCE), keratocytes (HK) and conjunctival fibroblasts (HConF). Heat-inactivated PRGF preserves the content of most of the proteins and morphogens involved in its wound healing effects while reduces drastically the content of IgE and complement activity. Heat-inactivated PRGF eye drops increased proliferation and migration potential of ocular surface cells with regard to PRGF showing significant differences on proliferation and migration rate of HCE and HConF respectively. In summary, heat-inactivation of PRGF eye drops completely reduced complement activity and deceased significantly the presence of IgE, maintaining the biological activity of PRGF on ocular surface cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

The protective effect of platelet released growth factors and bone augmentation (Bio-Oss®) on ethanol impaired osteoblasts.

PubMed

Sönmez, Tolga Taha; Bayer, Andreas; Cremer, Tillman; Hock, Jennifer Vanessa Phi; Lethaus, Bernd; Kweider, Nisreen; Wruck, Christoph Jan; Drescher, Wolf; Jahr, Holger; Lippross, Sebastian; Pufe, Thomas; Tohidnezhad, Mersedeh

2017-11-01

Chronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss ® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss ® in ethanol (EtOH) treated osteoblasts. The SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss ® were assessed. The application of PRGF and Bio-Oss ® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss ® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss ® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells. These results indicate that the simultaneous application of PRGF and Bio-Oss ® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

Benefits of plasma rich in growth factors (PRGF) in skin photodamage: clinical response and histological assessment.

PubMed

Díaz-Ley, B; Cuevast, J; Alonso-Castro, L; Calvo, M I; Ríos-Buceta, L; Orive, G; Anitua, E; Jaén, P

2015-01-01

Skin ageing is characterized by small and fine wrinkles, roughness, laxity, and pigmentation as a result of epidermal thinning, collagen degradation, dermal atrophy, and fewer fibroblasts. Plasma rich in growth factors (PRGF) is an autologous plasma preparation enriched in proteins obtained from patient's own blood aimed at accelerating tissue repair and regeneration. To evaluate the benefits of PRGF in skin photodamage, 10 healthy volunteers were treated with three consecutive intradermal injections of PRGF in the facial area. Clinical outcomes and histological analysis were performed. A statistically significant increase in the epidermis and papillary dermis thickness was seen after PRGF treatment (p < 0.001). Skin thickening was observed in all patients studied, being more intense in the group of patients with photodamage (p < 0.001). After PRGF treatment, a reduction of the average area fraction of solar elastosis was observed in patients with clinical and histological signs of skin photodamage (p < 0.05).No changeswere observed in the number of CD31, XIIIa factor, cKit, CD10, nor p53-positive cells. The improvement score after PRGF use was 0.75 (9/12) for the group of patients with signs of skin photodamage. Intradermal PRGF infiltration appears to be an effective treatment for the photodamaged skin. © 2015 Wiley Periodicals, Inc.

Autologous method for ex vivo expansion of human limbal epithelial progenitor cells based on plasma rich in growth factors technology.

PubMed

Riestra, A C; Vazquez, N; Chacon, M; Berisa, S; Sanchez-Avila, R M; Orive, G; Anitua, E; Meana, A; Merayo-Lloves, J

2017-04-01

Develop an autologous culture method for ex vivo expansion of human limbal epithelial progenitor cells (LEPCs) using Plasma Rich in Growth Factors (PRGF) as a growth supplement and as a scaffold for the culture of LEPCs. LEPCs were cultivated in different media supplemented with 10% fetal bovine serum (FBS) or 10% PRGF. The outgrowths, total number of cells, colony forming efficiency (CFE), morphology and immunocytochemistry against p63- α and cytokeratins 3 and 12 (CK3-CK12) were analyzed. PRGF was also used to elaborate a fibrin membrane. The effects of the scaffold on the preservation of stemness and the phenotypic characterization of LEPCs were investigated through analysis of CK3-CK12, ABCG-2 and p63. LEPCs cultivated with PRGF showed a significantly higher growth area than FBS cultures. Moreover, the number of cells were also higher in PRGF than FBS, while displaying a better morphology overall. CFE was found to be also higher in PRGF groups compared to FBS, and the p63-α expression also differed between groups. LEPCs cultivated on PRGF membranes appeared as a confluent monolayer of cells and still retained p63 and ABCG-2 expression, being negative for CK3-CK12. PRGF can be used in corneal tissue engineering, supplementing the culture media, even in a basal media without any other additives, as well as providing a scaffold for the culture. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the Effect of Platelet-Released Growth Factor and Immediate Orthodontic Loading on the Removal Torque of Miniscrews.

PubMed

Bayani, Shahin; Masoomi, Fatemeh; Aghaabbasi, Sharereh; Farsinejad, Alireza

2016-01-01

The purpose of this study was to evaluate the effect of platelet-released growth factor (PRGF) and immediate orthodontic forces on the removal torque of miniscrews. This study was conducted on three male dogs aged 6 to 8 months with a body weight of 17.6 to 18.4 kg. Sixty miniscrews were inserted in the posterior aspect of the femur. There were four groups, including loaded miniscrews with application of PRGF, unloaded miniscrews without application of PRGF, unloaded miniscrews with PRGF, and loaded miniscrews without PRGF. Twenty miniscrews were inserted in the femoral bone of one foot of each dog, including all the aforementioned subgroups. After 12 weeks, the miniscrews were removed by a removal torque tester device and measured in newton centimeters. The mean removal torque values in four groups of immediately loaded screws with PRGF, unloaded screws with PRGF, immediately loaded screws without PRGF, and unloaded screws without PRGF were 19.68, 21.74, 13.65, and 15.46 Ncm, respectively. It was shown that the mean removal torque value for the group with PRGF was significantly higher than that in the other groups (P = .0001). Although there was a tendency toward a decrease in removal torque value with immediate loading, it was not statistically significant (P = .21). According to the results of this study, applying PRGF with miniscrews increased their stability, but the delivery of immediate force on miniscrews had no effect on the miniscrews' stability.

Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration.

PubMed

Paknejad, M; Shayesteh, Y Soleymani; Yaghobee, S; Shariat, S; Dehghan, M; Motahari, P

2012-01-01

Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Twelve New Zealand white rabbits were included in this randomized, blinded, prospective study. Four equal 3.3×6.6 mm cranial bone defects were created and immediately grafted with DBBM, PRGF+DBBM, PRGF+fibrin membrane and no treatment as control. The defects were evaluated with histologic and histomorphometric analysis performed 4 and 8 weeks later. Adding PRGF to DBBM led to increased bone formation as compared with the control group in 4- and 8-week intervals. In DBBM and PRGF+fibrin membrane samples, no significant increase was seen compared to the control group. There was also a significant increase in the rate of biodegradation of DBBM particles with the addition of PRGF in the 8-week interval. Neither noticeable foreign body reaction nor any severe inflammation was seen in each of the specimens evaluated. Under the limitation of this study, adding PRGF to DBBM enhanced osteogenesis in rabbit calvarias. Applying autologous fibrin membrane in the defects was not helpful.

Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration

PubMed Central

Paknejad, M.; Shayesteh, Y. Soleymani; Yaghobee, S.; Shariat, S.; Dehghan, M.; Motahari, P.

2012-01-01

Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Materials and Methods: Twelve New Zealand white rabbits were included in this randomized, blinded, prospective study. Four equal 3.3×6.6 mm cranial bone defects were created and immediately grafted with DBBM, PRGF+DBBM, PRGF+fibrin membrane and no treatment as control. The defects were evaluated with histologic and histomorphometric analysis performed 4 and 8 weeks later. Results: Adding PRGF to DBBM led to increased bone formation as compared with the control group in 4- and 8-week intervals. In DBBM and PRGF+fibrin membrane samples, no significant increase was seen compared to the control group. There was also a significant increase in the rate of biodegradation of DBBM particles with the addition of PRGF in the 8-week interval. Neither noticeable foreign body reaction nor any severe inflammation was seen in each of the specimens evaluated. Conclusion: Under the limitation of this study, adding PRGF to DBBM enhanced osteogenesis in rabbit calvarias. Applying autologous fibrin membrane in the defects was not helpful. PMID:22924103

Infiltration of plasma rich in growth factors enhances in vivo angiogenesis and improves reperfusion and tissue remodeling after severe hind limb ischemia.

PubMed

Anitua, Eduardo; Pelacho, Beatriz; Prado, Roberto; Aguirre, José Javier; Sánchez, Mikel; Padilla, Sabino; Aranguren, Xabier L; Abizanda, Gloria; Collantes, María; Hernandez, Milagros; Perez-Ruiz, Ana; Peñuelas, Ivan; Orive, Gorka; Prosper, Felipe

2015-03-28

PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Plasma Rich in Growth Factors Inhibits Ultraviolet B Induced Photoageing of the Skin in Human Dermal Fibroblast Culture.

PubMed

Anitua, Eduardo; Pino, Ander; Orive, Gorka

Ultraviolet irradiation is able to deeply penetrate into the dermis and alter fibroblast structure and function, leading to a degradation of the dermal extracellular matrix. The regenerative effect of plasma rich in growth factors (PRGF) on skin ageing was investigated using UVB photo-stressed human dermal fibroblasts as an in vitro culture model. PRGF was assessed over the main indicative features of ultraviolet B irradiation, including ROS formation, cell viability and death detection, apoptosis/ necrosis analysis and biosynthetic activity measurement. Four different UV irradiation protocols were tested in order to analyze the beneficial effects of PRGF. Ultraviolet irradiation exhibited a dose dependent cytotoxicity and dose of 400mJ/cm2 was selected for subsequent experiments. PRGF increased the cell viability and decreased the cell death comparing to the non-treated group. The apoptosis and necrosis were significantly lower in PRGF treated fibroblasts. ROS production after UV irradiation was significantly reduced in the presence of PRGF. Procollagen type I, hyaluronic acid and TIMP-1 levels were higher in the when treated with PRGF. This preliminary in vitro study suggests that PRGF is able to prevent UVB derived photooxidative stress and to diminish the cell damage caused by ultraviolet irradiation.

Role of platelet-released growth factors in detoxification of reactive oxygen species in osteoblasts.

PubMed

Tohidnezhad, Mersedeh; Wruck, Christoph-Jan; Slowik, Alexander; Kweider, Nisreen; Beckmann, Rainer; Bayer, Andreas; Houben, Astrid; Brandenburg, Lars-Ove; Varoga, Deike; Sönmez, Tolga-Taha; Stoffel, Marcus; Jahr, Holger; Lippross, Sebastian; Pufe, Thomas

2014-08-01

Oxidative stress can impair fracture healing. To protect against oxidative damage, a system of detoxifying and antioxidative enzymes works to reduce the cellular stress. The transcription of these enzymes is regulated by antioxidant response element (ARE). The nuclear factor (erythroid-derived 2)-like2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes. Recently it has been shown that vascular endothelial growth factor (VEGF) prevents oxidative damage via activation of the Nrf2 pathway in vitro. Platelet-released growth factor (PRGF) is a mixture of autologous proteins and growth factors, prepared from a determined volume of platelet-rich plasma (PRP). It has already used to enhance fracture healing in vitro. The aim of the present study was to elucidate if platelets can lead to upregulation of VEGF and if platelets can regulate the activity of Nrf2-ARE system in primary human osteoblast (hOB) and in osteoblast-like cell line (SAOS-2). Platelets and PRGF were obtained from healthy human donors. HOB and SAOS-2 osteosarcoma cell line were used. The ARE activity was analysed using a dual luciferase reporter assay system. We used Western blot to detect the nuclear accumulation of Nrf2 and the amount of cytosolic antioxidant Thioredoxin Reductase-1 (TXNRD-1), Heme Oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO1). Gene expression analysis was performed by real-time RT PCR. ELISA was used for the quantification of growth factors. The activity of ARE was increased in the presence of PRGF up to 50%. Western blotting demonstrated enhanced nuclear accumulation of Nrf2. This was followed by an increase in the protein expression of the aforementioned downstream targets of Nrf2. Real-time RT PCR data showed an upregulation in the gene expression of the VEGF after PRGF treatment. This was confirmed by ELISA, where the treatment with PRGF induced the protein level of VEGF in both cells. These results provide a new insight into PRGF's mode of action in osteoblasts. PRGF not only leads to increase the endogenous VEGF, but also it may be involved in preventing oxidative damage through the Nrf2-ARE signalling. Nrf2 activation via PRGF may have great potential as an effective therapeutic drug target in fracture healing. Copyright © 2014 Elsevier Inc. All rights reserved.

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells.

PubMed

Mellado-López, Maravillas; Griffeth, Richard J; Meseguer-Ripolles, Jose; Cugat, Ramón; García, Montserrat; Moreno-Manzano, Victoria

2017-01-01

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100  μ M of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

Electrospun silk fibroin/poly (L-lactide-ε-caplacton) graft with platelet-rich growth factor for inducing smooth muscle cell growth and infiltration

PubMed Central

Yin, Anlin; Bowlin, Gary L.; Luo, Rifang; Zhang, Xingdong; Wang, Yunbing; Mo, Xiumei

2016-01-01

The construction of a smooth muscle layer for blood vessel through electrospinning method plays a key role in vascular tissue engineering. However, smooth muscle cells (SMCs) penetration into the electrospun graft to form a smooth muscle layer is limited due to the dense packing of fibers and lack of inducing factors. In this paper, silk fibroin/poly (L-lactide-ε-caplacton) (SF/PLLA-CL) vascular graft loaded with platelet-rich growth factor (PRGF) was fabricated by electrospinning. The in vitro results showed that SMCs cultured in the graft grew fast, and the incorporation of PRGF could induce deeper SMCs infiltrating compared to the SF/PLLA-CL graft alone. Mechanical properties measurement showed that PRGF-incorporated graft had proper tensile stress, suture retention strength, burst pressure and compliance which could match the demand of native blood vessel. The success in the fabrication of PRGF-incorporated SF/PLLA-CL graft to induce fast SMCs growth and their strong penetration into graft has important application for tissue-engineered blood vessels. PMID:27482466

Electrospun silk fibroin/poly (L-lactide-ε-caplacton) graft with platelet-rich growth factor for inducing smooth muscle cell growth and infiltration.

PubMed

Yin, Anlin; Bowlin, Gary L; Luo, Rifang; Zhang, Xingdong; Wang, Yunbing; Mo, Xiumei

2016-12-01

The construction of a smooth muscle layer for blood vessel through electrospinning method plays a key role in vascular tissue engineering. However, smooth muscle cells (SMCs) penetration into the electrospun graft to form a smooth muscle layer is limited due to the dense packing of fibers and lack of inducing factors. In this paper, silk fibroin/poly (L-lactide-ε-caplacton) (SF/PLLA-CL) vascular graft loaded with platelet-rich growth factor (PRGF) was fabricated by electrospinning. The in vitro results showed that SMCs cultured in the graft grew fast, and the incorporation of PRGF could induce deeper SMCs infiltrating compared to the SF/PLLA-CL graft alone. Mechanical properties measurement showed that PRGF-incorporated graft had proper tensile stress, suture retention strength, burst pressure and compliance which could match the demand of native blood vessel. The success in the fabrication of PRGF-incorporated SF/PLLA-CL graft to induce fast SMCs growth and their strong penetration into graft has important application for tissue-engineered blood vessels.

Enhanced proliferation and progesterone production by porcine granulosa cells cultured with pseudorabies virus growth factor (PRGF).

PubMed

Piekło, R; Gregoraszczuk, E L; Lesko, J; Golais, F; Stokłosowa, S

1999-03-01

The objective of this research was to study possible interactions of pseudorabies virus growth factor (PRGF) with ovarian tissue. Granulosa cells isolated from porcine ovaries were cultured as monolayers for 6 days in a control medium without PRGF and in medium supplemented with different doses of this agent. Increased population density and change towards more fibroblastic-like shape of cells cultured with 10(9) I.U PRGF was observed when compared with control culture. The cells divided significantly faster during 6 days of culture under the influence of 10(3), 10(4), 10(5), 10(6), 10(7), 10(8) and 10(9) I.U./ml of PRGF at a dose dependent manner. PRGF in a dose 10(9) I.U. added to cultured cells isolated from small and medium follicles did not influence progesterone secretion . An increase of progesterone secretion under the influence of PRGF in all investigated days of cultures was observed in cells isolated from large preovulatory follicles. The marked increase in progesterone content in PRGF treated culture in doses of 0.5x10(7), 0.5x10(8), 0.5x10(9) I.U. was observed during 4 and 6 days of culture. The rise of progesterone content was not connected with increased number of secretory cells, but with a stimulation of production per cell. PRGF exerted no visible effect on progesterone secretion by granulosa cells from small and medium follicles cultured for 6 days. The presented in vitro data provide evidence for a local action of PRGF in the follicle depending on the stage of follicular development and duration of exposure. Precise relevance of the interaction of PRGF with follicular development requires further study.

Plasma Rich in Growth Factors for the Treatment of Dry Eye after LASIK Surgery.

PubMed

Sanchez-Avila, Ronald Mauricio; Merayo-Lloves, Jesus; Fernandez, Maria Laura; Rodriguez-Gutierrez, Luis Alberto; Jurado, Nancy; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-06-08

The aim of this study was to evaluate the use of plasma rich in growth factors (PRGF) eye drops in patients with dry eye disease after laser-assisted in situ keratomileusis (LASIK) surgery. This is a longitudinal, retrospective, comparative, and descriptive study of 77 eyes of 42 patients with dry eye disease following LASIK surgery. This study was designed to evaluate the efficacy of PRGF treatment compared to conventional therapy (control group). Outcome measures including signs and symptoms of dry eye disease were evaluated before and after treatment. The percentage of change before and after treatment for each clinical variable measured was compared between both groups. There were 1-4 treatment cycles with PRGF eye drops (1 cycle = 6 weeks). Results showed a statistically significant improvement in the Ocular Surface Disease Index (38.12%), visual analogue scale scores for frequency (41.89%) and severity (42.47%), and the Schirmer test scores (88.98%) after PRGF treatment (p < 0.05). No adverse events were reported after PRGF treatment. These results suggest that PRGF eye drops are effective for the improvement of dry eye symptoms in patients who underwent LASIK surgery in comparison to the conventional therapy. The treatment with PRGF is an alternative for patients who suffer from postoperative dry eye. © 2018 S. Karger AG, Basel.

Dual effect of pseudorabies virus growth factor (PRGF) displayed on actin cytoskeleton.

PubMed

Urbancíková, M; Vozárová, G; Lesko, J; Golais, F

1999-10-01

Pseudorabies virus growth factor (PRGF) was shown to possess transforming activity as well as transformation repressing activity in in vitro systems. In order to better understand these phenomena we studied actin cytoskeleton and its alterations induced by PRGF using normal human fibroblasts VH-10 and transformed cell line HeLa. For specific detection of filamentous actin cells were stained with phalloidin conjugated with fluorescein isothiocyanate (FITC)-phalloidin. PRGF was applied to VH-10 cells for various length of time from 10 min up to 48 h. The effect was very fast and changes in actin filament composition could be detected already after 10 min. In comparison to untreated cells the staining of treated cells was more diffuse and a number of actin microfilaments in individual stress fibers became reduced. After 30 min thick short actin bundles appeared in the perinuclear region. A 24-h exposure resulted in a large reduction of actin bundles. After additional 24 h a partial restoration of actin cytoskeleton in cells was observed. In transformed HeLa cells PRGF induced opposite process than in normal cells: the number of filamentous actin structures increased. We hypothesise that PRGF may act as a transcription-like factor and may initiate changes in gene expression which consequently result in actin cytoskeleton alterations.

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone.

PubMed

Rivera, César; Monsalve, Francisco; Salas, Juan; Morán, Andrea; Suazo, Iván

2013-12-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H 2 O (n=3), distilled water without the drug and alveolar bone damage; BD/H 2 O/PRP (n=3), BD and PRP; BD/H 2 O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects.

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone

PubMed Central

RIVERA, CÉSAR; MONSALVE, FRANCISCO; SALAS, JUAN; MORÁN, ANDREA; SUAZO, IVÁN

2013-01-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H2O (n=3), distilled water without the drug and alveolar bone damage; BD/H2O/PRP (n=3), BD and PRP; BD/H2O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects. PMID:24250728

Plasma Rich in Growth Factors for the Treatment of Ocular Surface Diseases.

PubMed

Anitua, Eduardo; Muruzabal, Francisco; de la Fuente, María; Merayo, Jesús; Durán, Juan; Orive, Gorka

2016-07-01

The purpose of this work is to describe and review the technology of plasma rich in growth factors (PRGF), a novel blood derivative product, in the treatment of ocular surface disorders. To demonstrate the importance of this technology in the treatment of ocular pathologies, a thorough review of the preclinical and clinical literature results obtained following use of the different therapeutic formulations of PRGF was carried out. A literature search for applications of PGRF plasma in the ophthalmology field was carried out using the PubMed database. PRGF involves the use of patient's own biologically active proteins, growth factors, and biomaterial scaffolds for therapeutic purposes. This procedural technology is gaining interest in regenerative medicine due to its potential to stimulate and accelerate the tissue healing processes. The versatility and biocompatibility of this technology opens the door to a personalized medicine on ocular tissue regeneration. This review discusses the state of the art of the new treatments and technologies developed to promote ocular surface tissue regeneration. The standardized protocol that has been developed to source eye drops from PRGF technology is also described. The preclinical research, together with the most relevant clinical applications are summarized and discussed. The preliminary results suggest that the use of PRGF to enhance ocular tissue regeneration is safe and efficient.

Antibacterial effect of plasma rich in growth factors (PRGF®-Endoret®) against Staphylococcus aureus and Staphylococcus epidermidis strains.

PubMed

Anitua, E; Alonso, R; Girbau, C; Aguirre, J J; Muruzabal, F; Orive, G

2012-08-01

Formulations containing plasma rich in growth factors (PRGF) are opening new avenues in the field of regenerative medicine. To evaluate the potential antimicrobial effects of a product (plasma rich in growth factors; PRGF(®)-Endoret(®)) against both methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. The potential effect of incorporating the patient's leucocytes into the PRGF formulation (F3+leu) was also studied. Blood samples were obtained from five healthy volunteers and used to prepare each type of PRGF (F1, F3 and F3+leu). Various biological assays were performed to compare the characteristics of the different formulations, including measurement of the concentration of platelets and leucocytes, and assays of coagulation. The microbiological activity of PRGF-Endoret against both staphylococcal strains was performed by counting the number of the surviving bacterial colonies after incubation at 0, 4 and 8 h with the different formulations. The three PRGF-Endoret formulations evaluated were enriched in platelets by 1.10, 2.57 and 1.89 times, respectively, and the leucocyte concentration in the F3+leu sample was increased by 3.9 times. We found that all formulations had a strong bacteriostatic effect, especially in the first 4 h after application. All formulations had an antibacterial effect at 4 h for three of the four strains, with the exception of methicillin-sensitive S. epidermidis. No differences in the bacterial inhibitory effect were found between the formulations. This is the first time different formulations of this product have been evaluated, and the results suggest that PRGF-Endoret could be used in the fight against postoperative and wound infections. © The Author(s). CED © 2012 British Association of Dermatologists.

Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells

PubMed Central

Mellado-López, Maravillas; Griffeth, Richard J.; Meseguer-Ripolles, Jose; García, Montserrat

2017-01-01

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death. PMID:29270200

Serum from plasma rich in growth factors regenerates rabbit corneas by promoting cell proliferation, migration, differentiation, adhesion and limbal stemness.

PubMed

Etxebarria, Jaime; Sanz-Lázaro, Sara; Hernáez-Moya, Raquel; Freire, Vanesa; Durán, Juan A; Morales, María-Celia; Andollo, Noelia

2017-12-01

To evaluate the regenerating potential and the mechanisms through which the autologous serum derived from plasma rich in growth factors (s-PRGF) favours corneal wound healing in vitro and in vivo. We compared the effect of various concentrations of s-PRGF versus fetal bovine serum (FBS) and control treatment in rabbit primary corneal epithelial and stromal cells and wounded rabbit corneas. Cell proliferation was measured using an enzymatic colorimetric assay. In vitro and in vivo wound-healing progression was assessed by image-analysis software. Migration and invasion were evaluated using transfilter assays. Histological structure was analysed in stained sections. Protein expression was evaluated by immunohistochemistry. s-PRGF promoted the robust proliferation of epithelial cultures at any concentration, similar to FBS. Likewise, s-PRGF and FBS produced similar re-epithelialization rates in in vitro wound-healing assays. In vivo, s-PRGF treatment accelerated corneal wound healing in comparison with control treatment. This difference was significant only for 100% s-PRGF treatment in our healthy rabbit model. Histological analysis confirmed normal epithelialization in all cases. Immunohistochemistry showed a higher expression of cytokeratins 3/76 and 15, zonula occludens-1 and alpha-smooth muscle actin proteins as a function of s-PRGF concentration. Notably, keratocyte density in the anterior third of the stroma increased with increase in s-PRGF concentration, suggesting an in vivo chemotactic effect of s-PRGF on keratocytes that was further confirmed in vitro. s-PRGF promotes proliferation and migration and influences limbal stemness, adhesion and fibrosis during corneal healing. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Comparison of the Regenerative Effects of Platelet-Rich Fibrin and Plasma Rich in Growth Factors on Injured Peripheral Nerve: An Experimental Study.

PubMed

Torul, Damla; Bereket, Mehmet Cihan; Onger, Mehmet Emin; Altun, Gamze

2018-04-20

The aim of this study was to investigate the effects of platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF) on peripheral nerve injury in the early period of healing. Thirty Wistar albino rats were used in this study. Rats were divided into control (C), damaged (D), PRF, and PRGF groups. The left sciatic nerves of each group were identified as group C. Crush-type injury was performed on the right sciatic nerves of the D, PRF, and PRGF groups. In the PRF and PRGF groups, blood 2 mL was obtained to prepare the PRF and PRGF and the biomaterials were applied to the injured nerve area. After 8 weeks, functional, electrophysiologic, and stereological evaluations were performed. For the electrophysiologic evaluation, the latency and amplitude values in the D, PRF, and PRGF groups were significantly lower than those in the C group (P > .05). According to the sciatic functional index result, there were significant differences between groups D and PRF and between groups D and PRGF (P = .000). For the stereological evaluations, although no significant difference was observed between the PRGF and C groups (P > .05), a significant difference was observed among the D, PRF, and PRGF groups for myelinated axon number. There were significant differences between groups D and PRF and between groups D and PRGF for axon area (P = .021 and .001, respectively). No significant difference was observed among the D, PRF, and PRGF groups for myelin sheath thickness and ratio of axon area to myelin sheath thickness (P > .05). The results of this study suggest that PRGF increases nerve regeneration in the early period of healing and that the limited early action of PRF should be re-evaluated in the late period. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro.

PubMed

Bayer, Andreas; Tohidnezhad, Mersedeh; Berndt, Rouven; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Simanski, Maren; Gläser, Regine; Harder, Jürgen

2018-01-01

Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF ® ) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds. Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation. Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays. Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Histological study of the influence of plasma rich in growth factors (PRGF) on the healing of divided Achilles tendons in sheep.

PubMed

Fernández-Sarmiento, J Andrés; Domínguez, Juan M; Granados, María M; Morgaz, Juan; Navarrete, Rocío; Carrillo, José M; Gómez-Villamandos, Rafael J; Muñoz-Rascón, Pilar; Martín de Las Mulas, Juana; Millán, Yolanda; García-Balletbó, Montserrat; Cugat, Ramón

2013-02-06

The use of plasma rich in growth factors (PRGF) has been proposed to improve the healing of Achilles tendon injuries, but there is debate about the effectiveness of this therapy. The objective of the present study was to evaluate the histological effects of PRGF, which is a type of leukocyte-poor platelet-rich plasma, on tendon healing. The Achilles tendons of twenty-eight sheep were divided surgically. The animals were randomly divided into four groups of seven animals each. The repaired tendons in two groups received an infiltration of PRGF intraoperatively and every week for the following three weeks under ultrasound guidance. The tendons in the other two groups received injections with saline solution. The animals in one PRGF group and one saline solution group were killed at four weeks, and the animals in the remaining two groups were killed at eight weeks. The Achilles tendons were examined histologically, and the morphometry of fibroblast nuclei was calculated. The fibroblast nuclei of the PRGF-treated tendons were more elongated and more parallel to the tendon axis than the fibroblast nuclei of the tendons in the saline solution group at eight weeks. PRGF-treated tendons showed more packed and better oriented collagen bundles at both four and eight weeks. In addition to increased maturation of the collagen structure, fibroblast density was significantly lower in PRGF-infiltrated tendons. PRGF-treated tendons exhibited faster vascular regression than tendons in the control groups, as demonstrated by a lower vascular density at eight weeks. PRGF was associated with histological changes consistent with an accelerated early healing process in repaired Achilles tendons in sheep after experimental surgical disruption. PRGF-treated tendons showed improvements in the morphometric features of fibroblast nuclei, suggesting a more advanced stage of healing. At eight weeks, histological examination revealed more mature organization of collagen bundles, lower vascular densities, and decreased fibroblast densities in PRGF-treated tendons than in tendons infiltrated with saline solution. These findings were consistent with a more advanced stage of the healing process. Based on the findings in this animal model, PRGF infiltration may improve the early healing process of surgically repaired Achilles tendons.

Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation.

PubMed

Anitua, Eduardo; Sanchez, Mikel; Merayo-Lloves, Jesus; De la Fuente, Maria; Muruzabal, Francisco; Orive, Gorka

2011-08-01

Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGF-Endoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied. Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated. Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions. These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells.

Effect of plasma-rich in platelet-derived growth factors on peri-implant bone healing: An experimental study in canines

PubMed Central

Birang, Reza; Torabi, Alireza; Shahabooei, Mohammad; Rismanchian, Mansour

2012-01-01

Background: Tissue engineering principles can be exploited to enhance alveolar and peri-implant bone reconstruction by applying such biological factors as platelet-derived growth factors. The objective of the present study is to investigate the effect of autologous plasma-rich in growth factors (on the healing of peri-implant bone in canine mandible). Materials and Methods: In this prospective experimental animal study, two healthy canines of the Iranian mix breed were selected. Three months after removing their premolar teeth on both sides of the mandible, 12 implants of the Osteo Implant Corporationsystem, 5 mm in diameter and 10 mm in length, were selected to be implanted. Plasma rich in growth factors (PRGF) were applied on six implants while the other six were used as plain implants without the plasma. The implants were installed in osteotomy sites on both sides of the mandible to be removed after 4 weeks with the surrounding bones using a trephine bur. Mesio-distal sections and implant blocks, 50 μ in diameter containing the peri-implant bone, were prepared By basic fuchin toluidine-bluefor histological and histomorphometric evaluation by optical microscope. The data were analyzed using Mann-Whitney Test (P<0.05). Results: The bone trabeculae and the type of bone generation in PRGF and control groups had no statistically significant differences (P=0.261, P=0.2) although the parameters showed higher measured values in the PRGF group. However, compared to the control, application of PRGF had significantly increased bone-to-implant contact (P=0.028) Conclusion: Based on the results, it may be concluded that application of PRGF on the surface of implant may enhance bone-to-implant contact. PMID:22363370

The effects of PRGF on bone regeneration and on titanium implant osseointegration in goats: a histologic and histomorphometric study.

PubMed

Anitua, Eduardo; Orive, Gorka; Pla, Rafael; Roman, Pedro; Serrano, Victoriano; Andía, Isabel

2009-10-01

The effect of local application of scaffold-like preparation rich in growth factors (PRGF) on bone regeneration in artificial defects and the potential effect of humidifying titanium dental implants with liquid PRGF on their osseointegration were investigated. The PRGF formulations were obtained from venous blood of three goats and applied either as a 3D fibrin scaffold (scaffold-like PRGF) in the regeneration of artificial defects or as liquid PRGF via humidifying the implants before their insertion. Initially, 12 defects were filled with scaffold-like PRGF and another 12 were used as controls. The histological analysis at 8 weeks revealed mature bone trabeculae when PRGF was used, whereas the control samples showed mainly connective tissue with incipient signs of bone formation. For the second set of experiments, 26 implants (13 humidified with liquid PRGF) were placed in the tibiae of goats. Histological and histomorphometric results demonstrated that application of liquid PRGF increased the percentage of bone-implant contact in 84.7%. The whole surface of the PRGF-treated implants was covered by newly formed bone, whereas only the upper half was surrounded in control implants. In summary, PRGF can accelerate bone regeneration in artificial defects and improve the osseointegration of titanium dental implants.

Bilateral sinus elevation evaluating plasma rich in growth factors technology: a report of five cases.

PubMed

Anitua, Eduardo; Prado, Roberto; Orive, Gorka

2012-03-01

The purpose of this study was to evaluate the potential effects of plasma rich in growth factors (PRGF) technology and its autologous formulations in five consecutive patients in which bilateral sinus lift augmentation was carried out. Five consecutive patients received bilateral sinus floor augmentation. All patients presented a residual bone height of class D (1-3 mm). The effects of PRGF combined with bovine anorganic bone (one side) were compared with the biomaterial alone (contralateral side). The effects of using liquid PRGF to maintain the bone window and autologous fibrin membrane to seal the defect were evaluated. A complete histological and histomorphometrical analysis was performed 5 months after surgery. One patient was excluded from the study as the Schneiderian membrane of the control side was perforated during the surgery. In two patients, the biopsies obtained from the control sides 5 months postsurgery were not acceptable for processing. PRGF technology facilitated the surgical approach of sinus floor elevation. The control area was more inflamed than the area treated with PRGF technology. Patients referred also to an increased sensation of pain in the control area. PRGF-treated samples had more new vital bone than controls. In patient number 1, image processing revealed 21.4% new vital bone in the PRGF area versus 8.4% in the control area, whereas in patient number 2, 28.4% new vital bone was quantified in the PRGF area compared with the 8.2% of the control side. The immunohistochemical processing of the biopsies revealed that the number of blood vessels per square millimeter of connective tissue was 116 vessels in the PRGF sample versus 7 in the control biopsy. These preliminary results suggest that from a practical point of view, PRGF may present a role in reducing tissue inflammation after surgery, increasing new bone formation and promoting the vascularization of bone tissue. © 2010 Wiley Periodicals, Inc.

Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

PubMed

Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

2015-03-01

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

Incorporating Platelet-Rich Plasma into Electrospun Scaffolds for Tissue Engineering Applications

PubMed Central

Wolfe, Patricia S.; Ericksen, Jeffery J.; Simpson, David G.; Bowlin, Gary L.

2011-01-01

Platelet-rich plasma (PRP) therapy has seen a recent spike in clinical interest due to the potential that the highly concentrated platelet solutions hold for stimulating tissue repair and regeneration. The aim of this study was to incorporate PRP into a number of electrospun materials to determine how growth factors are eluted from the structures, and what effect the presence of these factors has on enhancing electrospun scaffold bioactivity. PRP underwent a freeze-thaw-freeze process to lyse platelets, followed by lyophilization to create a powdered preparation rich in growth factors (PRGF), which was subsequently added to the electrospinning process. Release of protein from scaffolds over time was quantified, along with the quantification of human macrophage and adipose-derived stem cell (ADSC) chemotaxis and proliferation. Protein assays demonstrated a sustained release of protein from PRGF-containing scaffolds at up to 35 days in culture. Scaffold bioactivity was enhanced as ADSCs demonstrated increased proliferation in the presence of PRGF, whereas macrophages demonstrated increased chemotaxis to PRGF. In conclusion, the work performed in this study demonstrated that the incorporation of PRGF into electrospun structures has a significant positive influence on the bioactivity of the scaffolds, and may prove beneficial in a number of tissue engineering applications. PMID:21679135

Coronally advanced flap and connective tissue graft with or without plasma rich in growth factors (PRGF) in treatment of gingival recession

PubMed Central

Jenabian, Niloofar; Motallebnejad, Mina; Zahedi, Ehsan; Angelov, Nikola

2018-01-01

Background Several researchers have tried to improve the results of gingival recession treatment techniques. One of the methods is to use growth factors The present study was undertaken to evaluate the effect of CAF (coronally advanced flap) + CTG (connective tissue graft) + PRGF (plasma rich in growth factors) in the treatment of Miller Class I buccal gingival recession. Material and Methods Twenty-two teeth with Miller Class I gingival recession in 6 patients 26 ‒ 47 years of age were included in a split-mouth designed randomized controlled trial (RCT). In each patient, one side was treated with CAF + CTG + PRGF (test) and the other side was treated with CAF + CTG (control). The following parameters were measured before surgery and up to 6 months after surgery on the mid-buccal surface of the tooth: keratinized tissue width (KTW), clinical attachment level (CAL), probing depth (PD), vertical recession depth (VRD), recession depth (RD), gingival thickness (GT), root coverage in percentage (RC%) and the distance between the CEJ and mucogingival junction (MGJL). Data were analyzed with paired t-test and repeated measures ANOVA. Results After 6 months noticeable improvements were observed in both groups in all the variables measured except for PD; however, the differences between the two groups were not significant. RC% was 80 ± 25% and 67 ± 28% in the test and control groups, respectively, after 6 months. Conclusions Both CAF + CTG + PRGF and CAF + CTG treatment modalities resulted in favorable root coverage; however, the addition of PRGF added no measurable significant effect. Key words:Connective tissue graft, dental root coverage, gingival recession, growth factors, mucogingival surgery, periodontal plastic surgery. PMID:29849966

Coronally advanced flap and connective tissue graft with or without plasma rich in growth factors (PRGF) in treatment of gingival recession.

PubMed

Jenabian, Niloofar; Motallebnejad, Mina; Zahedi, Ehsan; Sarmast, Nima D; Angelov, Nikola

2018-05-01

Several researchers have tried to improve the results of gingival recession treatment techniques. One of the methods is to use growth factors The present study was undertaken to evaluate the effect of CAF (coronally advanced flap) + CTG (connective tissue graft) + PRGF (plasma rich in growth factors) in the treatment of Miller Class I buccal gingival recession. Twenty-two teeth with Miller Class I gingival recession in 6 patients 26 ‒ 47 years of age were included in a split-mouth designed randomized controlled trial (RCT). In each patient, one side was treated with CAF + CTG + PRGF (test) and the other side was treated with CAF + CTG (control). The following parameters were measured before surgery and up to 6 months after surgery on the mid-buccal surface of the tooth: keratinized tissue width (KTW), clinical attachment level (CAL), probing depth (PD), vertical recession depth (VRD), recession depth (RD), gingival thickness (GT), root coverage in percentage (RC%) and the distance between the CEJ and mucogingival junction (MGJL). Data were analyzed with paired t-test and repeated measures ANOVA. After 6 months noticeable improvements were observed in both groups in all the variables measured except for PD; however, the differences between the two groups were not significant. RC% was 80 ± 25% and 67 ± 28% in the test and control groups, respectively, after 6 months. Both CAF + CTG + PRGF and CAF + CTG treatment modalities resulted in favorable root coverage; however, the addition of PRGF added no measurable significant effect. Key words: Connective tissue graft, dental root coverage, gingival recession, growth factors, mucogingival surgery, periodontal plastic surgery.

Effectiveness of platelet-rich plasma and hyaluronic acid for the treatment and care of pressure ulcers.

PubMed

Ramos-Torrecillas, Javier; García-Martínez, Olga; De Luna-Bertos, Elvira; Ocaña-Peinado, Francisco Manuel; Ruiz, Concepción

2015-03-01

Platelet-rich growth factor (PRGF) is a natural source of growth factors (GF), while hyaluronic acid (HA) is a biopolymer present in the extracellular matrix of skin, cartilage, bone, and brain, among other tissues. Both are involved in the pathophysiological mechanisms underlying wound healing. The objective of this study was to evaluate the clinical efficacy (as measured by ulcer area) and safety (as measured by signs of infection) of PRGF and PRGF plus HA in the treatment of pressure ulcers (PUs). Patients (N = 100) with 124 Stage II-III PUs were randomized to a control group (n = 25 PUs) for standard care or to case groups for treatment with one (n = 34 PUs) or two (n = 25 PUs) doses of PRGF from their own peripheral blood, or two doses of PRGF plus HA (n = 40 PUs). All ulcers were followed up every 3 days for a 36-day period. At 36 days, a significant reduction in ulcer area (p ≤ .001) was observed in all treatment groups, with a mean reduction of more than 48.0% versus baseline. The greatest mean reduction (80.4% vs. baseline) was obtained with the PRGF plus HA regimen. Complete wound healing was observed in 32.0% of PUs treated with two doses of PRGF (p ≤ .002) and in 37.5% of those treated with two doses of PRGF plus HA (p ≤ .004). There were no signs of infection in any PUs during the 36-day follow-up period. The degree of wound healing was inversely correlated with the consumption of drugs such as statins and with the peripheral blood platelet levels of patients at baseline. © The Author(s) 2014.

Expression of basic fibroblast growth factor mRNA in benign prostatic hyperplasia and prostatic carcinoma.

PubMed

Mydlo, J H; Michaeli, J; Heston, W D; Fair, W R

1988-01-01

In our previous work we demonstrated that prostate-derived growth factor (PrGF) is homologous to basic fibroblast growth factor (bFGF), not acidic fibroblast growth factor (aFGF). Using Northern blot analysis we now show that the messenger RNA for bFGF but not aFGF is expressed in benign prostatic hyperplastic (BPH) tissue as well as in carcinoma of the prostate (CAP). This not only corroborates our previous results, but suggests that PrGF is produced locally and not merely stored in the prostate. The demonstration of local production of bFGF by prostate tissue may indicate that this growth factor plays a role, either alone or in conjunction with other factors, in the etiology of benign hyperplasia or prostatic cancer.

Plasma rich in growth factors membrane as coadjuvant treatment in the surgery of ocular surface disorders.

PubMed

Sanchez-Avila, Ronald M; Merayo-Lloves, Jesús; Riestra, Ana C; Berisa, Silvia; Lisa, Carlos; Sánchez, José Alfonso; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-04-01

To evaluate the safety and efficacy of the surgical use of plasma rich in growth factors fibrin membrane (mPRGF) in different ocular surface pathologies.Fifteen patients with different corneal and conjunctival diseases were included in the study. Patients were grouped according to the use of mPRGF as graft (corneal and/or conjunctival) or dressing; they were also grouped according to the surgical subgroup of intervention (persistent corneal ulcer [PCU], keratoplasty, superficial keratectomy, corneal perforation, and pterygium). Best corrected visual acuity, intraocular pressure (IOP), inflammation control time (ICT), mPRGF AT (PRGF membrane absorption time), and the healing time of the epithelial defect (HTED) were evaluated throughout the clinical follow-up time. Safety assessment was also performed reporting all adverse events.mPRGF showed a total closure of the defect in 13 of 15 patients (86.7%) and a partial closure in 2 patients (13.3%). The mean follow-up time was 11.1 ± 4.2 (4.8-22.8) months, the mean ICT was 2.5 ± 1.1 (1.0-4.0) months, the mean mPRGF AT was 12.4 ± 2.0 (10.0-16.0) days, and for the global HTED the mean was 2.9 ± 1.2 (1-4.8) months. Results showed an improvement in BCVA in all patients, with an overall improvement of 2.9 in Vision Lines. The BCVA significantly improved (P < .05) in the groups of corneal graft and dressing. In the PCU subgroup (6 patients), the healing time of epithelial defect was significantly reduced (P < .05) in patients treated only with the mPRGF in comparison to those which mPRGF therapy was associated to the amniotic membrane. The IOP remained stable (P > .05) throughout the clinical follow-up time. No adverse events were reported after mPRGF use.The mPRGF is effective and safe as coadjuvant treatment in surgeries related with ocular surface disorders, being an alternative to the use of amniotic membrane. The mPRGF accelerates tissue regeneration after ocular surface surgery thus minimizing inflammation and fibrosis.

The Effect of Immunologically Safe Plasma Rich in Growth Factor Eye Drops in Patients with Sjögren Syndrome.

PubMed

Sanchez-Avila, Ronald Mauricio; Merayo-Lloves, Jesus; Riestra, Ana Cristina; Anitua, Eduardo; Muruzabal, Francisco; Orive, Gorka; Fernández-Vega, Luis

2017-06-01

The objective was to provide preliminary information about the efficacy and safety of immunologically safe plasma rich in growth factor (immunosafe PRGF) eye drops in the treatment of moderate to severe dry eye in patients with primary and secondary Sjögren's syndrome (SS) and to analyze the influence of several variables on treatment outcomes. This retrospective study included patients with SS. All patients were treated with previously immunosafe PRGF eye drops to reduce the immunologic component contents. Ocular Surface Disease Index (OSDI) scale, best-corrected visual acuity (BCVA), visual analog scale (VAS) frequency, and VAS severity outcome measures were evaluated before and after treatment with immunosafe PRGF. The potential influence of some patient clinical variables on results was also assessed. Safety assessment was also performed reporting all adverse events. Twenty-six patients (12 patients with primary SS, and 14 patients suffering secondary SS) with a total of 52 affected eyes were included and evaluated. Immunosafe PRGF treatment showed a significant reduction (P < 0.05) in OSDI scale (41.86%), in BCVA (62.97%), in VAS frequency (34.75%), and in VAS severity (41.50%). BCVA and VAS frequency scores improved significantly (P < 0.05) after concomitant treatment of PRGF with corticosteroids. Only 2 adverse events were reported in 2 patients (7.7% of patients). Signs and symptoms of dry eye syndrome in patients with SS were reduced after treatment with PRGF-Endoret eye drops. Immunosafe PRGF-Endoret is safe and effective for treating patients with primary and secondary SS.

Ultrasound-guided plasma rich in growth factors injections and scaffolds hasten motor nerve functional recovery in an ovine model of nerve crush injury.

PubMed

Sánchez, Mikel; Anitua, E; Delgado, D; Prado, R; Sánchez, P; Fiz, N; Guadilla, J; Azofra, J; Pompei, O; Orive, G; Ortega, M; Yoshioka, T; Padilla, S

2017-05-01

In the present study we evaluated the motor recovery process of peripheral nerve injury (PNI), based on electrophysiological and histomorphometric criteria, after treatment with plasma rich in growth factors (PRGF) injections and scaffolds in an ovine model. Three groups of sheep underwent a nerve crush lesion: the first group (n = 3) was left to recover spontaneously (SR); the second group was administered saline injections (SI; n = 5) and a third group (n = 6) received PRGF injections and scaffolds immediately after the crush injury. At post-intervention week 8, 70% of sheep in the PRGF group were CMAP-positive, with no electrophysiological response in the rest of the groups. Histomorphometric analysis 12 weeks after the surgical intervention revealed that the average axonal density of the SR (1184 ± 864 axons/µm 2 ) and SI (3109 ± 2450 axons/µm 2 ) groups was significantly inferior to the control (8427 ± 2433 axons/µm 2 ) and also inferior to the PRGF group (5276 ± 4148 axons/µm 2 ), showing no significant differences between the control and PRGF groups. The axonal size of the SR and SI groups was significantly smaller compared with the control group (18 ± 4 µm 2 ), whereas the axonal size of the PRGF group (6 ± 5 µm 2 ) did not show statistical differences from the control. Morphometry of the target muscles indicated that the PRGF group had the lowest percentage volume reduction 12 weeks after the crush injury. The PRGF group had larger muscle fibre areas than the SI and SR groups, although the differences did not reach statistical significance. Overall, these data suggest that the PRGF injections and scaffolds hastened functional axon recovery and dampened atrophy of the target muscles in an ovine model. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

PubMed Central

Tohidnezhad, Mersedeh; Lammel, Justus; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians' focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10) and late (transglutaminase-1 and involucrin) differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR-) dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo. PMID:28808357

Effect of plasma rich in growth factors on alveolar osteitis

PubMed Central

Haraji, Afshin; Lassemi, Eshagh; Motamedi, Mohammad Hosein Kalantar; Alavi, Maryam; Adibnejad, Saman

2012-01-01

Introduction: The high prevalence of dry socket or alveolar osteitis (AO) is of concern in surgical removal of third molars. The aim of the present study was to assess the preventive effect of plasma rich in growth factors (PRGF) on AO and also its effect on pain management and healing acceleration in third molar extraction sockets of high-risk patients. Materials and Methods: This split-mouth, double-blind clinical trial included 40 bilateral third molar extractions (80 sockets) with at least one identified risk factor for AO. PRGF was obtained from patient's own blood, based on manufacturer's instruction, and blindly placed in one of the two bilateral sockets (PRGF group; n = 20) of each patient. The contralateral socket was treated with a placebo (control group; n = 20). Samples were evaluated for AO and pain incidence on days 2, 3 and 4 and healing and infection on days 3 and 7. Data were analyzed in SPSS v16 using Wilcoxon test. Results: There was a significant difference in dry socket and pain incidence and healing rate between the two groups. Intensity of pain and occurrence of dry socket in the study group was lower than the controls. Also the healing rate was higher (P < 0.05) for the PRGF group. No sign of infection was seen in either group. Conclusion: The application of PRGF may significantly reduce the incidence of AO or its associated pain and may accelerate healing. The prophylactic use of PRGF following third molar extraction may be suggested especially in the patients at risk of AO. PMID:23251056

Comparison of the effects of platelet-rich or growth factor-rich plasma on intestinal anastomosis healing in pigs.

PubMed

Giusto, Gessica; Vercelli, Cristina; Iussich, Selina; Tursi, Massimiliano; Perona, Giovanni; Gandini, Marco

2017-06-19

The use of autologous platelet-rich plasma (PRP) and plasma rich in growth factors (PRGF) has been proposed for the treatment of several acute and chronic syndromes, such as corneal epithelial defects and dry eye syndrome, gum bleeding during oral surgery, and in orthopaedic surgery. We hypothesized that PRGF, rather than PRP, could be more effective because of its intrinsic characteristics in promoting the healing of intestinal anastomosis. The purpose of the present study was to evaluate and compare the effects of PRP and PRGF on various parameters of anastomotic healing in a swine model. Eight female pigs were randomly assigned to two groups and subjected to hand sewn jeujuno-jejunal appositional extramucosal anastomoses. For each animal, a total of six anastomoses were performed: two were considered controls and received no treatment, while the remaining four anastomoses were treated with PRP or PRGF of which both were prepared at a platelet concentration that was respectively 3.4-fold and 2.81-fold higher than the original platelet count. In each animal, either PRP or PRGF was used as a treatment, to avoid interference among products. Animals were euthanized after 8 days and the anastomoses were evaluated and compared for the presence of adhesions, anastomotic leakage, bursting pressure, and histological appearance. The concentration of platelets in PRP was 3.41-fold higher (range, 3.20-4.24) that the concentration in whole blood, while the concentration in PRGF was 2.81-fold higher (range, 2.89-4.88). The results obtained from the present study highlighted that there are no differences between anastomotic samples treated with either PRP or PRGF preparations, except for a significant increase in epithelization of the intestinal mucosa at the anastomotic site in the PRGF group. Both PRP and PRGF suspensions should be considered a safe strategy and represent a relatively low-cost technology that is flexible enough to be applied in several therapeutic fields. No true benefit could be proven in our study compared to the no treatment following anastomoses formation, with the exception of enhanced epithelization of the mucosa in the PRGF group.

Subepithelial connective tissue graft with and without the use of plasma rich in growth factors for treating root exposure

PubMed Central

Lafzi, Ardeshir; Shirmohammadi, Adileh; Behrozian, Ahmad; Kashefimehr, Atabak; Khashabi, Ehsan

2012-01-01

Purpose The aim of this study was to evaluate the clinical efficiency of the subepithelial connective tissue graft (SCTG) with and without plasma rich in growth factor (PRGF) in the treatment of gingival recessions. Methods Twenty bilateral buccal gingival Miller's Class I and II recessions were selected. Ten of the recessions were treated with SCTG and PRGF (test group). The rest ten of the recessions were treated with SCTG (control group). The clinical parameters including recession depth (RD), percentage of root coverage (RC), mucogingival junction (MGJ) position, clinical attachment level (CAL), and probing depth (PD) were measured at the baseline, and 1 and 3 months later. The data were analyzed using the Wilcoxon signed rank and Mann-Whitney U tests. Results After 3 months, both groups showed a significant improvement in all of the mentioned criteria except PD. Although the amount of improvement was better in the SCTG+PRGF group than the SCTG only group, this difference was not statistically significant. The mean RC was 70.85±12.57 in the test group and 75.83±24.68 in the control group. Conclusions Both SCTG+PRGF and SCTG only result in favorable clinical outcomes, but the added benefit of PRGF is not evident. PMID:23346462

The Efficacy of Plasma Rich in Growth Factors for the Treatment of Alveolar Osteitis: A Randomized Controlled Trial.

PubMed

King, Elizabeth M; Cerajewska, Tanya L; Locke, Matthew; Claydon, Nicholas C A; Davies, Maria; West, Nicola X

2018-06-01

To investigate the efficacy of plasma rich in growth factors (PRGF; BTI Biotechnology Institute, San Antonio, Spain) for the treatment of alveolar osteitis compared with a positive control (Alvogyl; Septodont, Maidstone, Kent, UK). This single-center, single-blinded, randomized, 2-treatment, parallel study was conducted in a UK dental hospital. All healthy adults who presented with alveolar osteitis after tooth extraction over a 3-month period were invited to participate. Each socket was randomized and treated with 1 of 2 treatment modalities, a test treatment (PRGF) or a positive control (Alvogyl). After treatment, patients were reviewed at 3 and 7 days by a second clinician blinded to the treatment given. Outcome measures included pain, exposed bone, inflammation, halitosis, dysgeusia, and quality-of-life assessment. Thirty-eight patients with data from 44 sockets (22 in the PRGF group and 22 in the Alvogyl group) were analyzed. The PRGF group showed significantly faster bone coverage and significantly decreased inflammation and halitosis (P < .05) compared with the control group receiving Alvogyl. There was no significant difference for pain, quality-of-life measures, or dysgeusia between groups. PRGF predictably treated alveolar osteitis after tooth extraction compared with the conventional standard treatment of Alvogyl, which has been used for many years. PRGF could be considered an alternative treatment for alveolar osteitis and indeed appears to have considerable advantages over Alvogyl. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Plasma Rich in Growth Factors Enhances Wound Healing and Protects from Photo-oxidative Stress in Dermal Fibroblasts and 3D Skin Models.

PubMed

Anitua, Eduardo; Pino, Ander; Jaen, Pedro; Orive, Gorka

2016-01-01

Optimal skin repair has been a desired goal for many researchers. Recently, plasma rich in growth factors (PRGF) has gained importance in dermatology proving it is beneficial effects in wound healing and cutaneous regeneration. The anti-fibrotic, pro-contractile and photo-protective effect of PRGF on dermal fibroblasts and 3D skin models has been evaluated. The effect against TGFβ1 induced myofibroblast differentiation was tested. Cell contractile activity over collagen gel matrices was analyzed and the effect against UV derived photo-oxidative stress was assessed. The effectiveness of PRGF obtained from young aged and middle aged donors was compared. Furthermore, 3D organotypic skin explants were used as human skin models with the aim of analyzing ex vivo cutaneous preventive and regenerative photo-protection after UV exposure. TGFβ1 induced myofibroblast levels decreased significantly after treatment with PRGF while the contractile activity increased compared to the control group. After UV irradiation, cell survival was promoted while apoptotic and ROS levels were noticeably reduced. Photo-exposed 3D explants showed higher levels of metabolic activity and lower levels of necrosis, cell damage, irritation and ROS formation when treated with PRGF. The histological integrity and connective tissue fibers showed lower signals of photodamage among PRGF injected skin models. No significant differences for the assessed biological outcomes were observed when PRGF obtained from young aged and middle aged donors were compared. These findings suggest that this autologous approach might be useful for antifibrotic wound healing and provide an effective protection against sun derived photo-oxidative stress regardless the age of the patient.

Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life.

PubMed

Wang-Saegusa, Ana; Cugat, Ramón; Ares, Oscar; Seijas, Roberto; Cuscó, Xavier; Garcia-Balletbó, Montserrat

2011-03-01

Osteoarthritis (OA) is a highly prevalent, chronic, degenerative condition that generates a high expense. Alternative and co-adjuvant therapies to improve the quality of life and physical function of affected patients are currently being sought. A total of 808 patients with knee pathology were treated with PRGF (plasma rich in growth factors), 312 of them with OA of the knee (Outerbridge grades I-IV) and symptoms of >3 months duration met the inclusion criteria and were evaluated to obtain a sample of 261 patients, 109 women and 152 men, with an average age of 48.39. Three intra-articular injections of autologous PRGF were administered at 2-week intervals in outpatient surgery. The process of obtaining PRGF was carried out following the Anitua Technique. Participants were asked to fill out a questionnaire with personal data and the following assessment instruments: VAS, SF-36, WOMAC Index and Lequesne Index before the first infiltration of PRGF and 6 months after the last infiltration. Statistically significant differences (P < 0.0001) between pre-treatment and follow-up values were found for pain, stiffness and functional capacity in the WOMAC Index; pain and total score, distance and daily life activities in the Lequesne Index; the VAS pain score; and the SF-36 physical health domain. There were no adverse effects related to PRGF infiltration. At 6 months following intra-articular infiltration of PRGF in patients with OA of the knee, improvements in function and quality of life were documented by OA-specific and general clinical assessment instruments. These favourable findings point to consider PRGF as a therapy for OA.

Comparison between autogenous iliac bone and freeze-dried bone allograft for repair of alveolar clefts in the presence of plasma rich in growth factors: A randomized clinical trial.

PubMed

Shirani, Gholamreza; Abbasi, Amir J; Mohebbi, Simin Z; Moharrami, Mohammad

2017-10-01

This study aimed to compare the effectiveness of alveolar cleft repair using iliac bone and freeze-dried bone allograft (FDBA) in the presence of plasma rich in growth factors (PRGF). Patients with unilateral alveolar cleft (n = 32) were randomly allocated to either the iliac plus PRGF group or the FDBA plus PRGF group. CBCT images were obtained before and 6 months after the surgery to assess the regenerated bone volume. Paired t-tests and two-way analysis of variance (ANOVA) were applied to analyze the data using SPSS 16.0 software. The patients' mean age was 15 ± 5.7 years (range = 8-27). In the iliac plus PRGF group, the mean volume of cleft before the surgery and the mean regenerated bone volume 6 months after were 1.67 ± 0.66 and 1.14 ± 0.47 cm 3 , respectively. The corresponding values were 1.5 ± 0.54 and 0.72 ± 0.23 cm 3 in the FDBA plus PRGF group. The remaining bone to cleft volume ratio was not associated with grafting time (secondary or tertiary) and the original cleft volume. Iliac bone reinforced with PRGF was more successful than FDBA plus PRGF in repairing alveolar cleft (p = 0.007). Due to the poor performance of the allograft, autografts should still be preferred in spite of possible donor site morbidity. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Wound healing with PRGF infiltration in CO(2) laser lesions of the tongue: an animal study.

PubMed

Camacho-Alonso, Fabio; López-Jornet, Pía; Jiménez-Torres, María José; Orduña-Domingo, Albina

2009-06-01

This study was done of the effects of plasma rich in growth factors (PRGF) on the healing of tongue wounds induced by the CO(2) laser. A prospective blind study was made of 60 Sprague-Dawley rats divided into two groups after the creation of tongue lesions using the CO(2) laser. Nothing was applied to the resulting wounds in the first group, while PRGF was applied to the 30 wounds in the second group. Wound re-epithelialization and inflammation were measured after 7, 14, and 28 d. No significant differences were seen between the two groups in relation to wound re-epithelialization, and the group without PRGF actually showed significantly better resolution of the inflammatory process after 14 d (p = 0.036). After 28 d, the rat tongue wounds produced by the CO(2) laser showed complete healing, independently of PRGF application.

Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery.

PubMed

Anitua, E; Muruzabal, F; Alcalde, I; Merayo-Lloves, J; Orive, G

2013-10-01

This study evaluated the efficacy of Plasma rich in growth factors (PRGF-Endoret) on the corneal wound healing process after Photorefractive keratectomy (PRK). To address this, blood from three healthy donors was collected, centrifuged and, the whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were collected. The effects of F3 and WP on the proliferation and migration of human corneal epithelial cells (HCE) were analyzed. PRK was performed on C57BL/6 mice. Animals were divided in three treatment groups: Control, F3, and WP. Corneal wound healing and haze formation were evaluated macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and were processed for histological studies. Immunofluorescence was used to assess cellular proliferation, apoptosis and myofibroblast transformation in the mouse cornea. Results showed a significant increased on proliferation and wound healing after F3 and WP treatment when compared with control group. In vivo studies showed significant reduction on haze formation in mice treated with both PRGF-Endoret formulations (F3 and WP). Histological studies showed an increase of epithelial cell proliferation in corneas of control group, promoting an epithelial hyperplasia. The number of SMA-positive cells (corresponding to myofibroblast differentiation) was significantly lower in the PRGF-Endoret group than in the control group, correlating with the higher transparence results observed macroscopically in both PRGF-Endoret groups. According to this, it can be concluded that PRGF-Endoret accelerates corneal tissue regeneration after PRK, reducing haze formation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficacy of plasma-rich growth factor in the healing of postextraction sockets in patients affected by insulin-dependent diabetes mellitus.

PubMed

Mozzati, Marco; Gallesio, Giorgia; di Romana, Sara; Bergamasco, Laura; Pol, Renato

2014-03-01

To evaluate the efficacy of plasma-rich growth factor (PRGF) in improving socket healing after tooth extraction in diabetic patients. This was a split-mouth study in which each patient also served as the control: the study socket was treated with PRGF, whereas the control socket underwent natural healing. The outcome variables were the Healing Index, residual socket volume, visual analog scale score, postsurgical complications, and outcome of a patient questionnaire. The investigation considered the impact of hyperglycemia, glycated hemoglobin, End Organ Disease Score, and smoking habits. Follow-up included 4 postextraction checkups over a 21-day period. Pairs of correlated continuous variables were analyzed with the Wilcoxon test, independent continuous variables with the Mann-Whitney test, and categorical variables with the χ(2) test or Fisher test. From January 2012 to December 2012, 34 patients affected by insulin-dependent diabetes mellitus underwent contemporary bilateral extractions of homologous teeth. The treatment-versus-control postoperative comparison showed that PRGF resulted in significantly smaller residual socket volumes and better Healing Indices from days 3 to 14. The patients' questionnaire outcomes were unanimously in favor of PRGF treatment. The small sample of patients with glycemia values of at least 240 mg/dL showed worse Healing Index and minor socket decreases. PRGF application after extraction improved the healing process in diabetic patients by accelerating socket closure (epithelialization) and tissue maturation, proving the association between PRGF use and improved wound healing in diabetic patients. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Ultrasound-guided platelet-rich plasma injections for the treatment of common peroneal nerve palsy associated with multiple ligament injuries of the knee.

PubMed

Sánchez, M; Yoshioka, T; Ortega, M; Delgado, D; Anitua, E

2014-05-01

Peroneal nerve palsy in traumatic knee dislocations associated with multiple ligament injuries is common. Several surgical approaches are described for this lesion with less-than-optimal outcomes. The present case represents the application of plasma rich in growth factors (PRGF) technology for the treatment of peroneal nerve palsy with drop foot. This technology has already been proven its therapeutic potential for various musculoskeletal disorders. Based on these results, we hypothesized that PRGF could stimulate the healing process of traumatic peroneal nerve palsy with drop foot. The patient was a healthy 28-year-old man. He suffered peroneal nerve palsy with drop foot after multiple ligament injuries of the knee. PRGF was prepared according to the manufactured instruction. Eleven months after the trauma with severe axonotmesis, serial intraneural infiltrations of PRGF were started using ultrasound guidance. The therapeutic effect was assessed by electromyography (EMG), echogenicity of the peroneal nerve under ultrasound (US) and manual muscle testing. Twenty-one months after the first injection, not complete but partial useful recovery is obtained. He is satisfied with walking and running without orthosis. Sensitivity demonstrates almost full recovery in the peroneal nerve distribution area. EMG controls show complete reinnervation for the peroneus longus and a better reinnervation for the tibialis anterior muscle, compared with previous examinations. Plasma rich in growth factors (PRGF) infiltrations could enhance healing process of peroneal nerve palsy with drop foot. This case report demonstrates the therapeutic potential of this technology for traumatic peripheral nerve palsy and the usefulness of US-guided PRGF. V.

Socket preservation using freeze-dried bone allograft with and without plasma rich in growth factors in dogs

PubMed Central

Samandari, Mohammad Hasan; Haghighat, Abbas; Torabinia, Nakisa; Taghian, Mehdi; Sadri, Leyli; Naemy, Vahid

2016-01-01

Background: Plasma rich in growth factors (PRGF) and freeze-dried bone allograft (FDBA) are shown to promote bone healing. This study was aimed to histologically and histomorphometrically investigate the effect of combined use of PRGF and FDBA on bone formation, and compare it to FDBA alone and control group. Materials and Methods: The distal roots of the lower premolars were extracted bilaterally in four female dogs. Sockets were randomly divided into FDBA + PRGF, FDBA, and control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 4 weeks. Sockets were assessed histologically and histomorphometrically. Data were analyzed by Kruskal–Wallis test followed by Mann–Whitney U-tests utilizing the SPSS software version 20. P < 0.05 was considered statistically significant. Results: While the difference in density of fibrous tissue in three groups was not statistically significant (P = 0.343), the bone density in grafted groups was significantly higher than the control group (P = 0.021). The least decrease in all socket dimensions was observed in the FDBA group. However, these differences were only significant in coronal portion at week 4. Regarding socket dimensions and bone density, the difference between FDBA and FDBA+PRGF groups was not significant in middle and apical portions. Conclusion: The superiority of PRGF+FDBA overFDBA in socket preservation cannot be concluded from this experiment. PMID:27857769

PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model.

PubMed

Anitua, E; Muruzabal, F; de la Fuente, M; Riestra, A; Merayo-Lloves, J; Orive, G

2016-10-01

Ocular graft versus host disease (oGVHD) is part of a systemic inflammatory disease that usually affects ocular surface tissues manifesting as a dry eye syndrome. Current treatments provide unsatisfactory results. Blood-derived products, like plasma rich in growth factors (PRGF) emerge as a potential therapy for this disease. The purpose of this study was to evaluate the tissue regeneration and anti-inflammatory capability of PRGF, an autologous platelet enriched plasma eye-drop, compared to autologous serum (AS) obtained from oGVHD patients on ocular surface cells cultured in a pro-inflammatory environment. PRGF and AS were obtained from four GVHD patients. Cell proliferation and inflammation markers, intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2), were measured in corneal and conjunctival fibroblastic cells cultured under pro-inflammatory conditions and after treatment with PRGF or AS eye drops. Moreover, cell proliferation increased after treatment with PRGF and AS, though this enhancement in the case of keratocytes was significantly higher with PRGF. PRGF eye drops showed a significant reduction of both inflammatory markers with respect to the initial inflammatory situation and to the AS treatment. Our results concluded that PRGF exerts more potent regenerative and anti-inflammatory effects than autologous serum on ocular surface fibroblasts treated with pro-inflammatory IL-1β and TNFα. Copyright © 2016 Elsevier Ltd. All rights reserved.

A preliminary study on the potential of manuka honey and platelet-rich plasma in wound healing.

PubMed

Sell, Scott A; Wolfe, Patricia S; Spence, Andrew J; Rodriguez, Isaac A; McCool, Jennifer M; Petrella, Rebecca L; Garg, Koyal; Ericksen, Jeffery J; Bowlin, Gary L

2012-01-01

Aim. The purpose of this study was to determine the in vitro response of cells critical to the wound healing process in culture media supplemented with a lyophilized preparation rich in growth factors (PRGF) and Manuka honey. Materials and Methods. This study utilized cell culture media supplemented with PRGF, as well as whole Manuka honey and the medical-grade Medihoney (MH), a Manuka honey product. The response of human fibroblasts (hDF), macrophages, and endothelial cells (hPMEC) was evaluated, with respect to cell proliferation, chemotaxis, collagen matrix production, and angiogenic potential, when subjected to culture with media containing PRGF, MH, Manuka honey, and a combination of PRGF and MH. Results. All three cell types demonstrated increases in cellular activity in the presence of PRGF, with further increases in activity seen in the presence of PRGF+MH. hDFs proved to be the most positively responsive cells, as they experienced enhanced proliferation, collagen matrix production, and migration into an in vitro wound healing model with the PRGF+MH-supplemented media. Conclusion. This preliminary in vitro study is the first to evaluate the combination of PRGF and Manuka honey, two products with the potential to increase regeneration individually, as a combined product to enhance dermal regeneration.

A Preliminary Study on the Potential of Manuka Honey and Platelet-Rich Plasma in Wound Healing

PubMed Central

Sell, Scott A.; Wolfe, Patricia S.; Spence, Andrew J.; Rodriguez, Isaac A.; McCool, Jennifer M.; Petrella, Rebecca L.; Garg, Koyal; Ericksen, Jeffery J.; Bowlin, Gary L.

2012-01-01

Aim. The purpose of this study was to determine the in vitro response of cells critical to the wound healing process in culture media supplemented with a lyophilized preparation rich in growth factors (PRGF) and Manuka honey. Materials and Methods. This study utilized cell culture media supplemented with PRGF, as well as whole Manuka honey and the medical-grade Medihoney (MH), a Manuka honey product. The response of human fibroblasts (hDF), macrophages, and endothelial cells (hPMEC) was evaluated, with respect to cell proliferation, chemotaxis, collagen matrix production, and angiogenic potential, when subjected to culture with media containing PRGF, MH, Manuka honey, and a combination of PRGF and MH. Results. All three cell types demonstrated increases in cellular activity in the presence of PRGF, with further increases in activity seen in the presence of PRGF+MH. hDFs proved to be the most positively responsive cells, as they experienced enhanced proliferation, collagen matrix production, and migration into an in vitro wound healing model with the PRGF+MH-supplemented media. Conclusion. This preliminary in vitro study is the first to evaluate the combination of PRGF and Manuka honey, two products with the potential to increase regeneration individually, as a combined product to enhance dermal regeneration. PMID:23304152

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

PubMed Central

Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680

Platelet released growth factors boost expansion of bone marrow derived CD34(+) and CD133(+) endothelial progenitor cells for autologous grafting.

PubMed

Lippross, Sebastian; Loibl, Markus; Hoppe, Sven; Meury, Thomas; Benneker, Lorin; Alini, Mauro; Verrier, Sophie

2011-01-01

Stem cell based autologous grafting has recently gained mayor interest in various surgical fields for the treatment of extensive tissue defects. CD34(+) and CD133(+) cells that can be isolated from the pool of bone marrow mononuclear cells (BMC) are capable of differentiating into mature endothelial cells in vivo. These endothelial progenitor cells (EPC) are believed to represent a major portion of the angiogenic regenerative cells that are released from bone marrow when tissue injury has occurred. In recent years tissue engineers increasingly looked at the process of vessel neoformation because of its major importance for successful cell grafting to replace damaged tissue. Up to now one of the greatest problems preventing a clinical application is the large scale of expansion that is required for such purpose. We established a method to effectively enhance the expansion of CD34(+) and CD133(+) cells by the use of platelet-released growth factors (PRGF) as a media supplement. PRGF were prepared from thrombocyte concentrates and used as a media supplement to iscove's modified dulbecco's media (IMDM). EPC were immunomagnetically separated from human bone morrow monocyte cells and cultured in IMDM + 10% fetal calf serum (FCS), IMDM + 5%, FCS + 5% PRGF and IMDM + 10% PRGF. We clearly demonstrate a statistically significant higher and faster cell proliferation rate at 7, 14, 21, and 28 days of culture when both PRGF and FCS were added to the medium as opposed to 10% FCS or 10% PRGF alone. The addition of 10% PRGF to IMDM in the absence of FCS leads to a growth arrest from day 14 on. In histochemical, immunocytochemical, and gene-expression analysis we showed that angiogenic and precursor markers of CD34(+) and CD133(+) cells are maintained during long-term culture. In summary, we established a protocol to boost the expansion of CD34(+) and CD133(+) cells. Thereby we provide a technical step towards the clinical application of autologous stem cell transplantation.

Effects of three blood derived products on equine corneal cells, an in vitro study.

PubMed

Rushton, J O; Kammergruber, E; Tichy, A; Egerbacher, M; Nell, B; Gabner, S

2018-05-01

Despite advances in therapy of corneal ulcerative diseases in horses, a vast number of cases require surgical intervention, due to poor response to treatment. Topical application of serum has been used for many years, based on its anticollagenolytic properties and the presence of growth factors promoting corneal wound healing. However, although other blood derived products i.e. platelet rich plasma (PRP), plasma rich in growth factors (PRGF) have been widely used in equine orthopaedics and in human ophthalmology, no reports of the effects of these blood derived products exist in equine ophthalmology. To determine in vitro effects of PRGF and PRP on equine corneal cells compared with serum. Prospective controlled cohort study. Blood from 35 healthy horses was used to produce serum, PRGF (Endoret ® ), and PRP (E-PET™). Limbal- and stromal cells were isolated from healthy corneas of six horses and treated with 20% serum, 20% PRGF or 20% PRP. Proliferation rates and migration capacity were analysed in single cell cultures as well as co-culture systems. Cell proliferation increased with PRP treatment, remained constant in PRGF treated cells, and declined upon serum treatment over a period of 48 h. Migration capacity was significantly enhanced with PRP treatment, compared with PRGF treatment. Intact leucocytes, mainly eosinophils, were only detected in PRP. Due to the study design use of autologous blood products on corneal cells was not possible. The results demonstrate beneficial effects of PRP on proliferation as well as migration capacity of equine corneal cells in vitro. In vivo studies are warranted to determine further beneficial effects of PRP in horses with corneal ulcers. © 2017 EVJ Ltd.

Comparative evaluation of zinc oxide eugenol versus gelatin sponge soaked in plasma rich in growth factor in the treatment of dry socket: An initial study

PubMed Central

Pal, U. S.; Singh, Balendra Pratap; Verma, Vikas

2013-01-01

Purpose: The aim of this study was to report a comparison between the zinc oxide eugenol dressing and plasma rich in growth factor (PRGF) with gelatin sponge in the treatment of dry socket. Materials and Methods: This study comprised of 45 patients of dry socket in the span of one year. The patients were randomly divided into three groups on the basis of treatments: Group A (PRGF with gelatin sponge), group B (zinc oxide eugenol group), and group C (irrigation with sterile saline only). The clinical progress was noted at 1st, 2nd, 3rd, 7th, and 15th day after the treatment. Results: Patient's healing was better in group A than in group B but symptomatic pain relief was faster in group B. Group C fared worst in both aspects. Conclusion: We conclude that PRGF with gelatin sponge might be a treatment of choice in the management of dry socket. PMID:23853450

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

PubMed Central

Rasuo, Biljana; Hock, Jennifer Vanessa Phi; Kweider, Nisreen; Fragoulis, Athanassios; Sönmez, Tolga Taha; Jahr, Holger; Pufe, Thomas; Lippross, Sebastian

2017-01-01

The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes. PMID:29348703

Bone regeneration with a combination of nanocrystalline hydroxyapatite silica gel, platelet-rich growth factor, and mesenchymal stem cells: a histologic study in rabbit calvaria.

PubMed

Behnia, Hossein; Khojasteh, Arash; Kiani, Mohammad Taghi; Khoshzaban, Ahad; Mashhadi Abbas, Fatemeh; Bashtar, Maryam; Dashti, Seyedeh Ghazaleh

2013-02-01

This study aimed to assess NanoBone as a carrier construct for mesenchymal stem cells (MSCs) and platelet-rich growth factor (PRGF). In the calvarial bone of 8 mature New Zealand White male rabbits, four 8-mm defects were created. Each defect received one of the following treatments: Group 1, 0.2 mg Nano-hydroxyapatite (HA) granule + 2 mL culture medium; Group 2, 0.2 mg Nano-HA + 1 mL autologous PRGF + 2 mL acellular culture medium; Group 3, 0.2 mg Nano-HA + 2 mL culture medium containing 100,000 autogenous MSCs; Group 4, 0.2 mg Nano-HA + 2 mL culture medium containing 100,000 autogenous MSCs + 1 mL autologous PRGF. Histomorphometric analysis at 6 and 12 weeks demonstrated significantly higher bone formation in group 4 (29.45% and 44.55%, respectively) (P < .05). Bone formation in groups 1, 2, and 3 were as follows: 11.35% and 32.53%, 29.10% and 39.74%, and 25.82% and 39.11%, respectively. NanoBone with MSCs and PRGF seems to be an effective combination for bone regeneration in a rabbit calvaria model. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of plasma rich in growth factors (PRGF) on biomechanical properties of Achilles tendon repair.

PubMed

López-Nájera, Diego; Rubio-Zaragoza, Mónica; Sopena-Juncosa, Joaquín J; Alentorn-Geli, Eduard; Cugat-Bertomeu, Ramón; Fernández-Sarmiento, J Andrés; Domínguez-Pérez, Juan M; García-Balletbó, Montserrat; Primo-Capella, Víctor J; Carrillo-Poveda, José M

2016-12-01

To assess the biomechanical effects of intra-tendinous injections of PRGF on the healing Achilles tendon after repair in a sheep model. Thirty sheep were randomly assigned into one of the six groups depending on the type of treatment received (PRGF or placebo) and survival time (2, 4 and 8 weeks). The Achilles tendon injury was repaired by suturing the tendinous edges employing a three-loop pulley pattern. A trans-articular external fixation system was then used for immobilization. The PRGF or placebo was administered on a weekly basis completing a maximum of three infiltrations. The force, section and tension values were compared between the operated and healthy Achilles tendons across all groups. The PRGF-treated tendons had higher force at 8 weeks compared with the placebo group (p = 0.007). Between 2 and 4 weeks, a significant increase in force in both the PRGF-treated tendon (p = 0.0027) and placebo group (p = 0.0095) occurred. No significant differences were found for section ratio between PRGF-treated tendons and the placebo group for any of the time periods evaluated. At 2 weeks, PRGF-treated tendons had higher tension ratio compared with placebo group tendons (p = 0.0143). Both PRGF and placebo treatments significantly improved the force (p < 0.001 and p = 0.0095, respectively) and tension (p = 0.009 and p = 0.0039, respectively) ratios at 8 weeks compared with 2 weeks. The application of PRGF increases Achilles tendon repair strength at 8 weeks compared with the use of placebo. The use of PRGF does not modify section and tension ratios compared with placebo at 8 weeks. The tension ratio progressively increases between 2 and 8 weeks compared with the placebo.

Efficacy and safety of plasma rich in growth factors intra-articular infiltrations in the treatment of knee osteoarthritis.

PubMed

Anitua, Eduardo; Sánchez, Mikel; Aguirre, José Javier; Prado, Roberto; Padilla, Sabino; Orive, Gorka

2014-08-01

The goal of this study was to systematically review the efficacy and safety of plasma rich in growth factors (PRGF) as a treatment for reducing symptoms in patients with knee osteoarthritis. A comprehensive and systematic literature search was conducted for PRGF treatment of knee osteoarthritis following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All the studies had to include a PRGF group and a control group. Pre- and post-treatment measures of joint pain, reduced function, and stiffness were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee score, Lequesne index, or number of Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI) responders, with a follow-up period of at least 4 weeks. An assessment of both the quality and risk of bias of the studies was conducted. The literature search yielded 91 citations, but only 5 were eligible publications that met the inclusion criteria (2 randomized controlled trials, 2 prospective studies, and 1 retrospective analysis). Two studies were rated as having a low risk of bias whereas 3 had a high risk. In both randomized controlled trials, it was observed that after 6 months of treatment, the number of patients with a pain reduction of more than 50% was significantly higher in the PRGF group. In 2 other studies, the patients treated with PRGF showed a significant pain reduction compared with the control group. The remaining variables (Western Ontario and McMaster Universities Osteoarthritis Index scale for pain, function, and stiffness; Lequesne index; Knee Injury and Osteoarthritis Outcome Score scale; and number of OMERACT-OARSI responders) showed a statistically significant superiority of the group treated with PRGF. The current clinical evidence suggests that PRGF intra-articular infiltrations in patients with knee osteoarthritis reduce pain and therefore are clinically efficacious in osteoarthritis treatment. Level III, systematic review of Level I, II, and III studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial.

PubMed

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P  = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P  = .001), respectively (between subjects P  = .631). There was no significant difference between PRGF and HA groups in patients' satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis.

Guided tissue regeneration and platelet rich growth factor for the treatment of Grade II furcation defects: A randomized double-blinded clinical trial - A pilot study.

PubMed

Jenabian, Niloofar; Haghanifar, Sina; Ehsani, Hodis; Zahedi, Ehsan; Haghpanah, Masumeh

2017-01-01

The treatment of furcation area defects remained as a challenging issue in periodontal treatments. Regeneration treatment of furcation defects is the most discussed periodontal treatment. Although not completely hopeless in prognosis, the presence of the furcation involvement significantly increases the chance of tooth loss. The current research was conductedeto compare theeadditive effect of combined guided tissue regeneration (GTR) and platelet-rich growth factor (PRGF) on the treatment of furcation bony defects. A randomized, triple-blinded, split-mouth study was designed. It included patients with a moderate to severe chronic periodontitis with bilateral Grade II furcation involvement of first or second mandibular molars. Each side of mouth was randomly allocated for the treatment with either Bio-Gide American Society of Anesthesiologists GTR or a PRGF or PRGF by itself. Plaque index, gingival index, vertical clinical attachment level, vertical probing depth, recession depth (REC), horizontal probing depth, fornix to alveolar crest (FAC), fornix to base of defect (FBD), furcation vertical component and furcation horizontal component (FHC) were recorded. The current research was conducted to compare the additive effect of combined GTR and PRGF on treatment of furcation bony defects. Altman's nomogram, Kolmogorov-Smirnov test, Friedman test, general linear model, repeated measures, and paired t -test were used as statistical analysis in this research. P < 0.05 was considered statistically significant. Eight patients were finally enrolled for this study. Overly, general and specific clinical and furcation parameters were improved except REC that was deteriorated insignificantly and FAC improved not significantly. Intergroup comparison revealed better improvement of FHC in GTR/PRGF group ( P = 0.02). A significant improvement in the Grade II furcation defects treated with either GTR or PRGF/GTR was noticed. Further large-scale trials are needed to reveal differences of mentioned treatment in more details.

Guided tissue regeneration and platelet rich growth factor for the treatment of Grade II furcation defects: A randomized double-blinded clinical trial - A pilot study

PubMed Central

Jenabian, Niloofar; Haghanifar, Sina; Ehsani, Hodis; Zahedi, Ehsan; Haghpanah, Masumeh

2017-01-01

Background: The treatment of furcation area defects remained as a challenging issue in periodontal treatments. Regeneration treatment of furcation defects is the most discussed periodontal treatment. Although not completely hopeless in prognosis, the presence of the furcation involvement significantly increases the chance of tooth loss. The current research was conductedeto compare theeadditive effect of combined guided tissue regeneration (GTR) and platelet-rich growth factor (PRGF) on the treatment of furcation bony defects. Materials and Methods: A randomized, triple-blinded, split-mouth study was designed. It included patients with a moderate to severe chronic periodontitis with bilateral Grade II furcation involvement of first or second mandibular molars. Each side of mouth was randomly allocated for the treatment with either Bio-Gide American Society of Anesthesiologists GTR or a PRGF or PRGF by itself. Plaque index, gingival index, vertical clinical attachment level, vertical probing depth, recession depth (REC), horizontal probing depth, fornix to alveolar crest (FAC), fornix to base of defect (FBD), furcation vertical component and furcation horizontal component (FHC) were recorded. The current research was conducted to compare the additive effect of combined GTR and PRGF on treatment of furcation bony defects. Altman's nomogram, Kolmogorov–Smirnov test, Friedman test, general linear model, repeated measures, and paired t-test were used as statistical analysis in this research. P < 0.05 was considered statistically significant. Results: Eight patients were finally enrolled for this study. Overly, general and specific clinical and furcation parameters were improved except REC that was deteriorated insignificantly and FAC improved not significantly. Intergroup comparison revealed better improvement of FHC in GTR/PRGF group (P = 0.02). Conclusion: A significant improvement in the Grade II furcation defects treated with either GTR or PRGF/GTR was noticed. Further large-scale trials are needed to reveal differences of mentioned treatment in more details. PMID:29238373

Clinical Comparison of Autogenous Bone Graft with and without Plasma Rich in Growth Factors in the Treatment of Grade II Furcation Involvement of Mandibular Molars

PubMed Central

Lafzi, Ardeshir; Shirmohammadi, Adileh; Faramarzi, Masoumeh; Jabali, Sahar; Shayan, Arman

2013-01-01

Background and aims Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors, which is used to promote periodontal tissue regeneration. The aim of this randomized, controlled, clinical trial was to evaluate of the treatment of grade II mandibular molar furcation involvement using autogenous bone graft with and without PRGF. Materials and methods In this double-blind clinical trial, thirty mandibular molars with grade II furcation involvement in 30 patients were selected. The test group received bone graft combined with PRGF, while the control group was treated with bone graft only. Clinical parameters included clinical probing depth (CPD), vertical clinical attachment level (V-CAL), horizontal clinical attachment level (H-CAL), location of gingival margin (LGM), surgically exposed horizontal probing depth of bony defect (E-HPD), vertical depth of bone crest (V-DBC), vertical depth of the base of bony defect (V-DBD), and length of the intrabony defect (LID). After six months, a re-entry surgery was performed. Data were analyzed by SPSS 14, using Kolmogorov, Mann-Whitney U, and paired t-test. Results After 6 months, both treatment methods led to significant improvement in V-CAL and H-CAL and significant decreases in CPD, E-HPD, V-DBD and LID; there was no significant difference in LGM and V-DBC in any of the treated groups compared to the baseline values. Also, none of the parameters showed significant differences between the study groups. Conclusion Although autogenous bone grafts, with or without PRGF, were successful in treating grade II furcation involvement, no differences between the study groups were observed. PMID:23486928

Plasma rich in growth factors had limited effect on early bone formation in extraction sockets: Response to "Anitua, E., Alkhraisat, M.H. & Orive, G. (2013) Letter to the Editor: Rigorous methodology is the school of coherent conclusions in science. European Journal of Oral Implantology 6: 9-11.".

PubMed

Farina, Roberto; Bressan, Eriberto; Taut, Andrei; Cucchi, Alessandro; Trombelli, Leonardo

2014-10-01

To address the criticisms raised by Anitua et al. (European Journal of Oral Implantology, 6, 2013, 9-11) to the article "Plasma Rich in Growth Factors (PRGF) in Human Post-Extraction Sockets: an Histological and Histomorphometric Study.", recently published by Farina and colleagues (Clinical Oral Implants Research 2012; doi: 10.1111/clr.12033). All the methodological aspects criticized in the letter by Anitua et al. were thoroughly reconsidered and discussed in a structured short communication. When indicated, pertinent, additional material was included to reinforce our considerations. As most clinical studies in implant dentistry, including previous studies evaluating the efficacy/effectiveness of PRGF, the study by Farina et al. has some limitations. However, it is currently the only published controlled trial using quantitative parameters related to PRGF-induced early bone formation. Despite all limitations, the results of the study by Farina et al., which were based on different quantitative parameters (micro-CT scan, immunohistochemical markers of wound healing and bone deposition), indicated a limited effect of PRGF on early bone formation in extraction sockets. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Effect of autologous platelet-rich plasma on heart infarction in sheep].

PubMed

Gallo, Ignacio; Sáenz, Alberto; Arévalo, Adolfo; Roussel, Sonia; Pérez-Moreiras, Ignacio; Artiñano, Edurne; Martínez-Peñuela, Ana; Esquide, Javier; Aspiroz, Antonio; Camacho, Ignacio

2013-01-01

Myocardial infarction is the most common cause of congestive heart failure. The objective of this work is to evaluate, in experimental animals, morphological and histological effects of the implantation of autologous platelet-rich plasma in infarcted heart sheep. Twenty-four ewes were used, they were surgically infarcted through left thoracotomy and two coronary arteries were ligated (first and second diagonal). After coronary artery ligation three sheep died of ventricular fibrillation. Three weeks after coronary ligation, sheep were reoperated through median sternotomy. Normal saline solution was injected in the infarcted zone in 6 of them (control group) whereas platelet gel was injected in 15 of them. All sheep were euthanized at 9 weeks of evolution of the second surgery. Noteworthy is the formation of new vessels in hematoxylin-eosin-stained sections and factor viii in plasma rich in growth-factors (PRGF)-treated hearts. Injection of platelet growth factors, PRGF, in previously infarcted sheep hearts promotes mitogenesis and angiogenesis. The use of autologous PRGF is simple and safe, causing no toxicity or immune-inflammatory reactions. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic-alginate composite thermogel.

PubMed

Segredo-Morales, Elisabet; García-García, Patricia; Reyes, Ricardo; Pérez-Herrero, Edgar; Delgado, Araceli; Évora, Carmen

2018-05-30

As the life expectancy of the world population increases, osteoporotic (OP) fracture risk increase. Therefore in the present study a novel injectable thermo-responsive hydrogel loaded with microspheres of 17β-estradiol, microspheres of bone morphogenetic protein-2 (BMP-2) and plasma rich in growth factors (PRGF) was applied locally to regenerate a calvaria critical bone defect in OP female rats. Three systems were characterized: Tetronic® 1307 (T-1307) reinforced with alginate (T-A), T-A with PRGF and T-A-PRGF with microspheres. The addition of the microspheres increased the viscosity but the temperature for the maximum viscosity did not change (22-24 °C). The drugs were released during 6 weeks in one fast phase (three days) followed by a long slow phase. In vivo evaluation was made in non-OP and OP rats treated with T-A, T-A with microspheres of 17β-estradiol (T-A-βE), T-A-βE prepared with PRGF (T-A-PRGF-βE), T-A-βE with microspheres of BMP-2 (T-A-βE-BMP-2) and the combination of the three (T-A-PRGF-βE-BMP). After 12 weeks, histological and histomorphometric analyzes showed a synergic effect due to the addition of BMP-2 to the T-A-βE formulation. The PRGF did not increased the bone repair. The new bone filling the OP defect was less mineralized than in the non-OP groups. Copyright © 2018 Elsevier B.V. All rights reserved.

Socket preservation using demineralized freezed dried bone allograft with and without plasma rich in growth factor: A canine study

PubMed Central

Mogharehabed, Ahmad; Birang, Reza; Torabinia, Nakisa; Nasiri, Saman; Behfarnia, Parichehr

2014-01-01

Background: The accelerating effect of plasma rich in growth factors (PRGFs) in the healing of extraction sockets has been demonstrated by some studies. The aim of the present study was to histologically and histomorphometrically evaluate whether bone formation would increase by the combined use of PRGF and demineralized freeze-dried bone allograft (DFDBA). Materials and Methods: In four female dogs, the distal root of the second, third and fourth lower premolars were extracted bilaterally and the mesial roots were preserved. The extraction sockets were randomly divided into DFDBA + PRGF, DFDBA + saline or control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 6 weeks. The extraction sockets were evaluated from both histological and histomorphometrical aspects. The data were analyzed by Mann-Whitney followed by Kruskal-Wallis tests using the Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA). Significant levels were set at 0.05. Results: The least decrease in socket height was observed in the DFDBA + PRGF group (0.73 ± 0.42 mm). The least decrease in the coronal portion was observed in the DFDBA + PRGF group (1.38 ± 1.35 mm²). The least decrease in the middle surface was observed in the DFDBA group (0.61 ± 0.80 mm²). The least decrease in the apical portion was observed in the DFDBA group (0.34 ± 0.39 mm²). Conclusion: The present study showed better socket preservation subsequent to the application of DFDBA and PRGF combination in comparison with the two other groups. However, the difference was not statistically significant. PMID:25225559

Effects of Plasma Rich in Growth Factors and Platelet-Rich Fibrin on Proliferation and Viability of Human Gingival Fibroblasts

PubMed Central

Vahabi, Surena; Vaziri, Shahram; Torshabi, Maryam

2015-01-01

Objectives: Platelet preparations are commonly used to enhance bone and soft tissue regeneration. Considering the existing controversies on the efficacy of platelet products for tissue regeneration, more in vitro studies are required. The aim of the present study was to compare the in vitro effects of plasma rich in growth factors (PRGF) and platelet-rich fibrin (PRF) on proliferation and viability of human gingival fibroblasts (HGFs). Materials and Methods: Anitua’s PRGF and Choukran’s PRF were prepared according to the standard protocols. After culture periods of 24, 48 and 72 hours, proliferation of HGFs was evaluated by the methyl thiazol tetrazolium assay. Statistical analysis was performed using one-way ANOVA followed by Tukey-Kramer’s multiple comparisons and P-values<0.05 were considered statistically significant. Results: PRGF treatment induced statistically significant (P<0.001) proliferation of HGF cells compared to the negative control (100% viability) at 24, 48 and 72 hours in values of 123%±2.25%, 102%±2.8% and 101%±3.92%, respectively. The PRF membrane treatment of HGF cells had a statistically significant effect on cell proliferation (21%±1.73%, P<0.001) at 24 hours compared to the negative control. However, at 48 and 72 hours after treatment, PRF had a negative effect on HGF cell proliferation and caused 38% and 60% decrease in viability and proliferation compared to the negative control, respectively. The HGF cell proliferation was significantly higher in PRGF than in PRF group (P< 0.001). Conclusion: This study demonstrated that PRGF had a strong stimulatory effect on HGF cell viability and proliferation compared to PRF. PMID:26877740

Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops.

PubMed

Sanchez-Avila, Ronald Mauricio; Merayo-Lloves, Jesus; Riestra, Ana Cristina; Fernandez-Vega Cueto, Luis; Anitua, Eduardo; Begoña, Leire; Muruzabal, Francisco; Orive, Gorka

2018-06-01

To provide preliminary data about efficacy and safety of plasma rich in growth factors (PRGF) eye-drops in neurotrophic keratitis (NK) and to analyze the possible influence of certain variables on treatment outcomes. This retrospective study included patients with stages 2-3 of NK treated with PRGF eye-drops. Primary endpoint was the resolution time of corneal ulcer defect. Outcome measures including percentage of ulcer closure at 4 weeks, Ocular Surface Disease Index (OSDI), Best-Corrected Visual Acuity (BCVA) and Visual Analogue Scale (VAS) were also evaluated before and after treatment with PRGF. The influence of some patients' clinical variables on results was assessed. Safety assessment was also performed reporting all adverse events. Thirty-eight treated eyes in a total of thirty-one patients were evaluated, of which five cases had no prior response to autologous serum treatment. Most cases (97.4%) achieved the complete resolution of corneal defect/ulcer. Mean resolution time was 11.4 weeks (SD = 13.7). A statistical significant (p < 0.05) reduction in OSDI (60.9%), VAS frequency (59.9%), VAS severity (57.0%) and improvement in BCVA (52.8%) was observed. The results were stratified according to the pathology stage and to the identified potential effect modifiers variables. Only one adverse event was reported in one patient (2.6%). PRGF eye-drops could be a safe and effective therapeutic option for patients with stages 2-3 of NK, showing high rates of corneal defect/ulcer resolution in short times, either in reducing signs and symptoms of NK, and therefore preventing the progression of NK to greater ocular complications.

Two cycles of plasma rich in growth factors (PRGF-Endoret) intra-articular injections improve stiffness and activities of daily living but not pain compared to one cycle on patients with symptomatic knee osteoarthritis.

PubMed

Vaquerizo, Víctor; Padilla, Sabino; Aguirre, José Javier; Begoña, Leire; Orive, Gorka; Anitua, Eduardo

2017-05-19

To assess the clinical efficacy and safety of a treatment based on one cycle versus two cycles of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) on patients with knee osteoarthritis (OA). Ninety patients with knee OA were included and evaluated. A total of 48 patients received one cycle (OC group) (3 injections on a weekly basis), while 42 patients received two cycles of PRGF-Endoret (TC group) spaced 6 months between them. Patients were evaluated with LEQUESNE and WOMAC scores before treatment and after 48 weeks. Safety assessment was also performed. A significant reduction of all assessed outcome measures was shown for both groups at 48 weeks compared with baseline values (P < 0.001). Patients of TCs group showed a significantly higher reduction (P < 0.05) in WOMAC stiffness subscales. Regarding LEQUESNE INDEX, a significantly higher reduction was observed in the TC group in all subscales except in pain score. In the maximum walking distance subscale (MCD), the improvement rate was 31.8% higher for the TCs group compared with the OC group (P < 0.01). In addition, the TC group showed a significant improvement in LEQUESNE activities of daily living (ADV) and global subscales of 14.7 and 11.8% (P < 0.05) higher, respectively, than the OC group. Treatment with two cycles of PRGF did not show a significantly higher pain reduction compared with one cycle treatment. However, two cycles of PRGF showed a significant improvement in WOMAC stiffness, LEQUESNE MCD, LEQUESNE ADV and LEQUESNE global subscales. Therefore, patients treated with two cycles present an improvement in quality of life. II.

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

PubMed

Sánchez, Mikel; Fiz, Nicolás; Azofra, Juan; Usabiaga, Jaime; Aduriz Recalde, Enmanuel; Garcia Gutierrez, Antonio; Albillos, Javier; Gárate, Ramón; Aguirre, Jose Javier; Padilla, Sabino; Orive, Gorka; Anitua, Eduardo

2012-08-01

This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. Level I, randomized controlled multicenter trial. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Central Asian Drug Trafficking Dilemma

DTIC Science & Technology

2003-12-01

Tajikistan’s economic difficulties. The IMF has approved a three-year, US$87 million dollar poverty reduction and growth facility ( PRGF ) arrangement for...contributing approximately US $11 million. The PRGF is the IMF’s concessional facility for low-income countries. The PRGF supported programs are based on...activities or paying dividends while it has negative net worth. In addition to the above measures provided by the PRGF , Tajikistan will continue to

Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo comparative study.

PubMed

Freire, Vanesa; Andollo, Noelia; Etxebarria, Jaime; Hernáez-Moya, Raquel; Durán, Juan A; Morales, María-Celia

2014-06-01

The aim of this study was to compare the effect on corneal wound healing of 3 differently manufactured blood derivatives [autologous serum (AS), platelet-rich plasma, and serum derived from plasma rich in growth factors (s-PRGF)]. Scratch wound-healing assays were performed on rabbit primary corneal epithelial cultures and human corneal epithelial cells. Additionally, mechanical debridement of rabbit corneal epithelium was performed. Wound-healing progression was assessed by measuring the denuded areas remaining over time after treatment with each of the 3 blood derivatives or a control treatment. In vitro data show statistically significant differences in the healing process with all the derivatives compared with the control, but 2 of them (AS and s-PRGF) induced markedly faster wound healing. In contrast, although the mean time required to complete in vivo reepithelization was similar to that of AS and s-PRGF treatment, only wounds treated with s-PRGF were significantly smaller in size from 2.5 days onward with respect to the control treatment. All 3 blood derivatives studied are promoters of corneal reepithelization. However, the corneal wound-healing progresses differently with each derivative, being faster in vitro under AS and s-PRGF treatment and producing in vivo the greatest decrease in wound size under s-PRGF treatment. These findings highlight that the manufacturing process of the blood derivatives may modulate the efficacy of the final product.

Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology.

PubMed

Sánchez, Mikel; Anitua, Eduardo; Azofra, Juan; Prado, Roberto; Muruzabal, Francisco; Andia, Isabel

2010-04-01

To investigate whether the application of a particular platelet-rich plasma preparation rich in growth factors (PRGF) during anterior cruciate ligament (ACL) surgery gives a potential advantage for better tendon graft ligamentization. This study included 37 volunteers who underwent either conventional (control group, n = 15) or PRGF-assisted (n = 22) ACL reconstruction with an autogenous hamstring and required second-look arthroscopy to remove hardware or loose bodies, treat meniscal tears or plica syndrome, or resect cyclops lesions at 6 to 24 months after ACL surgery. The gross morphologies of the grafts were evaluated on second-look arthroscopy by use of the full arthroscopic score (0 to 4 points) to evaluate graft thickness and apparent tension (0 to 2 points) plus synovial coverage (0 to 2 points). At the same time, biopsy specimens were harvested uniformly from the grafted tendons. In these specimens the histologic transformation of the tendon graft to ACL-like tissue was evaluated by use of the Ligament Tissue Maturity Index, and a score to assess the progression of new connective tissue enveloping the graft was created by use of 3 criteria previously used to characterize changes during ligament healing: cellularity, vascularity, and collagen properties. The overall arthroscopic evaluation of PRGF-treated grafts showed an excellent rating in 57.1% of the knees (score of 4) and a fair rating in 42.9% (score of 2 or 3). In contrast, evaluation of untreated grafts showed an excellent rating in 33.3% of the knees, a fair rating in 46.7%, and a poor rating in 20% (score of 0 or 1). Overall, arthroscopic evaluations were not statistically different between PRGF and control groups (P = .051). PRGF treatment influenced the histologic characteristics of the tendon graft, resulting in tissue that was more mature than in controls (P = .024). Histologically evident newly formed connective tissue enveloping the graft was present in 77.3% of PRGF-treated grafts and 40% of controls. The appearance of the connective tissue envelope changed with increasing time from surgery. On the basis of the histologic findings, we suggest that the remodeling of PRGF-treated grafts involves the formation of synovial-like tissue enveloping the graft. This tissue is eventually integrated in the remodeled tendon graft, conferring a similar appearance to the normal ACL. The use of PRGF influenced the histologic characteristics of tendon grafts, resulting in more remodeling compared with untreated grafts. We have shown temporal histologic changes during the 6- to 24-month postoperative period of graft maturation, with newly formed connective tissue enveloping most grafts treated with PRGF. Level III, case-control study. Copyright 2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial

PubMed Central

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Background and objectives: Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. Methods: In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. Results: A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively (between subjects P = .631). There was no significant difference between PRGF and HA groups in patients’ satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. Conclusions: In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis. PMID:29051707

State Capacity and Resistance in Afghanistan

DTIC Science & Technology

2009-03-01

PRGF )222 of the International Monetary Fund (IMF).223 Facing these self-imposed (internal) and international (external) constraints, budget and...Budget_Policy_Coord_Reporting/Fact _Sheet/Fact_sheet_final_1386.pdf (accessed 19 November 2008). 222 The PRGF provides aid and structural guidance in the...management. See: A Factsheet: The Poverty Reduction and Growth Facility ( PRGF ). (International Monetary Fund, October 2008). On the web: http

Additive Effect of Plasma Rich in Growth Factors With Guided Tissue Regeneration in Treatment of Intrabony Defects in Patients With Chronic Periodontitis: A Split-Mouth Randomized Controlled Clinical Trial.

PubMed

Ravi, Sheethalan; Malaiappan, Sankari; Varghese, Sheeja; Jayakumar, Nadathur D; Prakasam, Gopinath

2017-09-01

Periodontal regeneration can be defined as complete restoration of lost periodontal tissues to their original architecture and function. A variety of treatment modalities have been proposed to achieve it. Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors that promotes restoration of lost periodontal tissues. The objective of the present study is to assess the effect of PRGF associated with guided tissue regeneration (GTR) versus GTR only in the treatment of intrabony defects (IBDs) in patients with chronic periodontitis (CP). Patients with CP (n = 14) with 42 contralateral 2- and 3-walled defects were randomly assigned to test (PRGF+GTR) and control (GTR alone) treatment groups. Clinical and radiographic assessments performed at baseline and after 6 months were: 1) gingival index (GI), 2) probing depth (PD), 3) clinical attachment level (CAL), 4) radiologic defect depth, and 5) bone fill. Comparison of parameters measured at baseline and after 6 months showed mean PD reduction of 3.37 ± 1.62 mm in the control group (P <0.001) and 4.13 ± 1.59 mm in the test group (P <0.001). There was a significant difference in mean change in CAL (P <0.001) in the control group (5.42 ± 1.99) and the test group (5.99 ± 1.77). Mean change in GI was 1.89 ± 0.32 and 1.68 ± 0.58 in the control group and test group, respectively, and the difference was statistically significant (P <0.001). When compared between groups, clinical parameters did not show any statistically significant variations. Mean radiographic bone fill was 1.06 ± 0.81 and 1.0 ± 0.97 in the control group and test group, respectively. However, the difference was not statistically significant. PRGF with GTR, as well as GTR alone, was effective in improving clinical and radiographic parameters of patients with CP at the 6-month follow-up. There was no additive effect of PRGF when used along with GTR in the treatment of IBDs in patients with CP in terms of both clinical and radiologic outcomes.

Honduras: Political and Economic Situation and U.S. Relations

DTIC Science & Technology

2006-10-13

2006.6 Amid the country’s hurricane reconstruction efforts, Honduras signed a poverty reduction and growth facility ( PRGF ) agreement with the International...macroeconomic discipline and to develop a comprehensive poverty reduction strategy. In February 2004, Honduras signed a three-year PRGF agreement...IMF Executive Board Completes Third Program and Financing Assurances Reviews under Honduras’ PRGF Arrangement,” Press Release No. 05/280, Dec. 16, 2005

Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

PubMed Central

Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

2017-01-01

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients. PMID:28798878

Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

PubMed

Cugat, Ramón; Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

2017-01-01

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

Evaluation of autogenous PRGF+β-TCP with or without a collagen membrane on bone formation and implant osseointegration in large size bone defects. A preclinical in vivo study.

PubMed

Batas, Leonidas; Stavropoulos, Andreas; Papadimitriou, Serafim; Nyengaard, Jens R; Konstantinidis, Antonios

2016-08-01

The aim of this study was to evaluate whether the adjunctive use of a collagen membrane enhances bone formation and implant osseointegration in non-contained defects grafted with chair-side prepared autologous platelet-rich growth factor (PRGF) adsorbed on a β-TCP particulate carrier. Large box-type defects (10 × 6 mm; W × D) were prepared in the edentulated and completely healed mandibles of six Beagles dogs. An implant with moderately rough surface was placed in the center of each defect leaving the coronal 6 mm of the implant not covered with bone. The remaining defect space was then filled out with chair-side prepared autologous PRGF adsorbed on β-TCP particles and either covered with a collagen membrane (PRGF/β-TCP+CM) (6 defects) or left without a membrane (PRGF/β-TCP) (5 defects). Histology 4 months post-op showed new lamellar and woven bone formation encompassing almost entirely the defect and limited residual β-TCP particles. Extent of osseointegration of the previously exposed portion of the implants varied, but in general was limited. Within the defect, new mineralized bone (%) averaged 43.2 ± 9.86 vs. 39.9 ± 13.7 in the PRGF/β-TCP+CM and PRGF/β-TCP group (P = 0.22) and relative mineralized bone-to-implant contact (%) averaged 26.2 ± 16.45 vs. 35.91 ± 24.45, respectively (P = 0.5). First, bone-to-implant contact from the implant top was 4.1 ± 1.5 and 3.2 ± 2.3 (P = 0.9), in the PRGF/β-TCP+CM and PRGF/β-TCP group, respectively. Implantation of chair-side prepared autologous PRGF adsorbed on a β-TCP carrier in non-contained peri-implant defects resulted in large amounts of bone regeneration, but osseointegration was limited. Provisions for GBR with a collagen membrane did not significantly enhance bone regeneration or implant osseointegration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue

PubMed Central

Cocero, Nadia; Pucci, Fabrizio; Messina, Maria; Pollio, Berardino; Mozzati, Marco; Bergamasco, Laura

2015-01-01

Background Dental extractions in haemophiliacs may cause secondary bleeding, requiring repeated surgical and haematological interventions. As a local haemostatic, fibrin glue has recognised efficacy but, as a plasma-derived product, it carries the risk of viral infections. We, therefore, compared fibrin glue with an autologous haemostatic, plasma rich in growth factors (PRGF), in a controlled trial. Material and methods One hundred and twenty patients with different blood disorders were randomised into two cohorts to undergo dental extraction procedures without hospitalisation. Prior to the extractions, patients underwent systemic haematological treatment. Complications were defined as secondary bleeding after the 7-day follow-up period or protracting after the repair procedure. Results There were 106 extractions (7 retained 3rd molars) in the group managed with fibrin glue: secondary bleeding affected 3/60 patients (5%) on the third day after extraction and necessitated additional surgery and systemic treatment (in one case the procedure had to be repeated on the 7th day). In the PRGF arm there were 98 extractions (23 retained 3rd molars): secondary bleeding affected two patients (3.3%) on the first day after extraction and was arrested with surgery without systemic treatment. Four out of the five secondary bleeds occurred in patients with haemophilia A. Concomitant diabetes or liver disease significantly increased the bleeding risk. Discussion The bleeding rates in the study and control arm prove that PRGF works as well as fibrin glue as a local haemostatic. Further assets are that PRGF has autologous origin, does not require additional systemic treatment in post-extraction repair surgery, is associated with an earlier onset of neo-angiogenesis and, overall, can reduce patients’ distress and costs to the health system. PMID:25369587

Partial anterior cruciate ligament tears treated with intraligamentary plasma rich in growth factors

PubMed Central

Seijas, Roberto; Ares, Oscar; Cuscó, Xavier; Álvarez, Pedro; Steinbacher, Gilbert; Cugat, Ramón

2014-01-01

AIM: To evaluate the effect of the application of plasma rich in growth factors (PRGF)-Endoret to the remaining intact bundle in partial anterior cruciate ligament (ACL) tears. METHODS: A retrospective review of the rate of return to play in football players treated with the application of PRGF-Endoret in the remaining intact bundle in partial ACL injuries that underwent surgery for knee instability. Patients with knee instability requiring revision surgery for remnant ACL were selected. PRGF was applied in the wider part of posterolateral bundle and the time it took patients to return to their full sporting activities at the same level before the injury was evaluated. RESULTS: A total of 19 patients were reviewed. Three had a Tegner activity level of 10 and the remaining 16 level 9. The time between the injury and the time of surgery was 5.78 wk (SD 1.57). In total, 81.75% (16/19) returned to the same pre-injury level of sport activity (Tegner 9-10). 17 males and 2 females were treated. The rate of associated injury was 68.42% meniscal lesions and 26.31% cartilage lesions. The KT-1000 values were normalized in all operated cases. One patient was not able to return to sport due to the extent of their cartilage lesions. The 15 patients with Tegner activity level 9 returned to play at an average of 16.20 wk (SD 1.44) while the 3 patients with Tegner activity level 10 did so in 12.33 wk (SD 1.11). CONCLUSION: With one remaining intact bundle the application of PRGF-Endoret in instability cases due to partial ACL tear showed high return to sport rates at pre- injury level in professional football players. PMID:25035842

Growth factors delivery from hybrid PCL-starch scaffolds processed using supercritical fluid technology.

PubMed

Diaz-Gomez, Luis; Concheiro, Angel; Alvarez-Lorenzo, Carmen; García-González, Carlos A

2016-05-20

Synthetic polymeric scaffolds to be used as surrogates of autologous bone grafts should not only have suitable physicochemical and mechanical properties, but also contain bioactive agents such as growth factors (GFs) to facilitate the tissue growth. For this purpose, cost-effective and autologous GFs sources are preferred to avoid some post-surgery complications after implantation, like immunogenicity or disease transmission, and the scaffolds should be processed using methods able to preserve GFs activity. In this work, poly(ɛ-caprolactone) (PCL) scaffolds incorporating GFs were processed using a green foaming process based on supercritical fluid technology. Preparation rich in growth factors (PRGF), a natural and highly available cocktail of GFs obtained from platelet rich plasma (PRP), was used as GF source. PCL:starch:PRGF (85:10:5 weight ratio) porous solid scaffolds were obtained by a supercritical CO2-assisted foaming process at 100 bar and 37 °C with no need of post-processing steps. Bioactivity of GFs after processing and scaffold cytocompatibility were confirmed using mesenchymal stem cells. The performance of starch as GF control release component was shown to be dependent on starch pre-gelification conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Global Economic Crisis: Impact on Sub-Saharan Africa and Global Policy Responses

DTIC Science & Technology

2009-10-19

concessional lending facilities, the Poverty Reduction and Growth Facility ( PRGF ) and the Exogenous Shocks Facility (ESF).99 Figure 12. IMF Concessional Loans...to Africa Billions of Dollars Source: International Monetary Fund. Notes: Amounts are the total amount of outstanding PRGF and ESF loans to...99 PRGF loans are intended to help low-income countries address balance of payments concerns, such as those created by the financial crisis. Unlike

The Global Financial Crisis: Increasing IMF Resources and the Role of Congress

DTIC Science & Technology

2009-06-05

may borrow on concessional repayment terms from the Poverty Reduction and Growth Facility ( PRGF ) and the Exogenous Shocks Facility (ESF). To qualify...Association (IDA). Most borrowers have per capita income levels of about $865 a year. PRGF loans are intended to help low-income countries surmount BOP...or financial crises. Unlike SBA and other loans, however, conditionality for PRGF loans is based more on the economic strategies outlined in Poverty

The Global Economic Crisis: Impact on Sub-Saharan Africa and Global Policy Responses

DTIC Science & Technology

2010-04-06

financial assistance to Africa is provided through the IMF’s concessional lending facilities, the Poverty Reduction and Growth Facility ( PRGF ) and...Notes: Amounts are the total amount of outstanding PRGF and ESF loans to African countries at the end of April for each year...Report RS22534, The Multilateral Debt Relief Initiative, by Martin A. Weiss. 107 PRGF loans are intended to help low-income countries address

A lateral approach for sinus elevation using PRGF technology.

PubMed

Anitua, Eduardo; Prado, Roberto; Orive, Gorka

2009-10-01

A lateral approach for sinus elevation using plasma rich in growth factors (PRGF) technology is described. The long-term survival of dental implants installed following a two-stage procedure after sinus elevation using this procedure is reported, using implant loss as the outcome variable. A retrospective cohort study design was used. Eighteen patients received 43 implants (BTI implants, Biotechnology Institute, Vitoria, Spain) with sinus floor elevation. All patients presented a residual bone height of class D (1-3 mm). Implants were installed using a low-speed drilling procedure (50 rpm) without irrigation. Finally, the histological and histomorphometric evaluation of eight samples from PRGF grafted sinus involved in the study was carried out 5-6 months posttreatment. The overall survival rate of dental implants was 100%. The mean follow-up period for all implants was 33 +/- 7 months ranging from 24 to 44 months. In addition, the histomorphometrical evaluation of the samples evidenced a 25.24 +/- 4.62% of vital newly formed bone, 50.31 +/- 15.56% of soft connective tissue, and the remaining 24.46 +/- 12.79% of bovine anorganic bone. Based on these results, this new approach for sinus elevation and implant installation using PRGF technology can be considered safe, simple, effective, and predictable.

Treatment of hemimandibular paresthesia in a patient with bisphosphonate-related osteonecrosis of the jaw (BRONJ) by combining surgical resection and PRGF-Endoret.

PubMed

Anitua, E; Begoña, L; Orive, G

2013-12-01

We report a case of a 50-year-old patient with bisphosphonate-related osteonecrosis of the jaws (BRONJs) whose symptoms included severe pain and hemimandibular paraesthesia. The treatment included resection of necrotic bone and the application of plasma rich in growth factors (PRGF(®)-Endoret(®)). We closed the ulcer in the soft tissue and her pain and paraesthesia improved. One year postoperatively sensitivity was totally recovered, pain was absent and bone was partially regenerated. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Heparin-binding growth factor isolated from human prostatic extracts.

PubMed

Mydlo, J H; Bulbul, M A; Richon, V M; Heston, W D; Fair, W R

1988-01-01

Prostatic tissue extracts from patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma were fractionated using heparin-Sepharose chromatography. The mitogenic activity of eluted fractions on quiescent subconfluent Swiss Albino 3T3 fibroblasts was tested employing a tritiated-thymidine-incorporation assay. Two peaks of activity were consistently noted--one in the void volume and a second fraction which eluted with 1.3-1.6 M NaCl and contained the majority of the mitogenic activity. Both non-heparin- and heparin-binding fractions increased tritiated incorporation into a mouse osteoblast cell line (MC3T3), while only the heparin-binding fractions stimulated a human umbilical vein endothelial cell line (HUV). No increased uptake of thymidine was seen using a human prostatic carcinoma cell line (PC-3). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of lyophilized active fractions showed a persistent band at 17,500 daltons. The purified protein demonstrated angiogenic properties using the chick embryo chorioallantoic membrane (CAM) assay. Western blot analysis using antibodies specific to basic fibroblast growth factor (bFGF) or acidic FGF (aFGF) demonstrated that the former, but not the latter, bound to prostatic growth factor (PrGF), and inhibited its mitogenic activity as well. It appears that PrGF shares homology with basic fibroblast growth factors.

The Global Economic Crisis: Impact on Sub-Saharan Africa and Global Policy Responses

DTIC Science & Technology

2009-08-25

facilities, the Poverty Reduction and Growth Facility ( PRGF ) and the Exogenous Shocks Facility (ESF).88 Figure 11. IMF Concessional Loans to Africa...Billions of Dollars Source: International Monetary Fund. Notes: Amounts are the total amount of outstanding PRGF and ESF loans to African countries...the Needs of Low-Income Countries,” July 29, 2009. 87 CRS Report RS22534, The Multilateral Debt Relief Initiative, by Martin A. Weiss. 88 PRGF loans

Plasma rich in growth factors eye drops to treat secondary ocular surface disorders in patients with glaucoma

PubMed Central

Sánchez-Avila, Ronald M; Merayo-Lloves, Jesus; Fernández, Maria Laura; Rodríguez-Gutiérrez, Luis Alberto; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega Cueto, Andres; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-01-01

Purpose To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use. Materials and methods A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated. Results Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58–79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12–36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed (p<0.05). IOP also decreased by 16.6% (p=0.010). Only one of the six patients reported itching in both eyes as an adverse event (AE); however, the patient continued with the PRGF eye drops until the end of therapy; the remaining patients did not report any AEs during the follow-up period. Conclusions In patients with glaucoma and secondary OSDs refractive to conventional treatments, the treatment with PRGF eye drops could be considered a possible therapeutic option, because it demonstrates an improvement in the signs and symptoms of the ocular surface, as well as a better control of the IOP. This is an initial research work that can open doors for future research to confirm these findings. PMID:29760570

Plasma rich in growth factors eye drops to treat secondary ocular surface disorders in patients with glaucoma.

PubMed

Sánchez-Avila, Ronald M; Merayo-Lloves, Jesus; Fernández, Maria Laura; Rodríguez-Gutiérrez, Luis Alberto; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega Cueto, Andres; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-01-01

To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use. A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated. Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58-79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12-36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed ( p <0.05). IOP also decreased by 16.6% ( p =0.010). Only one of the six patients reported itching in both eyes as an adverse event (AE); however, the patient continued with the PRGF eye drops until the end of therapy; the remaining patients did not report any AEs during the follow-up period. In patients with glaucoma and secondary OSDs refractive to conventional treatments, the treatment with PRGF eye drops could be considered a possible therapeutic option, because it demonstrates an improvement in the signs and symptoms of the ocular surface, as well as a better control of the IOP. This is an initial research work that can open doors for future research to confirm these findings.

PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.

PubMed

Anitua, Eduardo; Zalduendo, Mar; Troya, María; Orive, Gorka

2016-04-01

Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

Biomolecules in the treatment of lichen planus refractory to corticosteroid therapy: Clinical and histopathological assessment.

PubMed

Piñas, Laura; Alkhraisat, Mohammad Hamdan; Suárez-Fernández, Ricardo; Anitua, Eduardo

2018-03-01

Local deficit of several biomolecules have been described in oral lichen planus (OLP). Such a deficit impairs cellular functions and cell-matrix communication. Assess the efficacy of the local application of autologous biomolecules in the treatment of erosive OLP. In this study, the use of plasma rich in growth factors (PRGF) as a source of blood-derived and autologous growth factors and proteins were tested in erosive oral lichen planus refractory to corticosteroids. Histopathological features of the disease were also analysed at the time of diagnosis. Clinical data were the number of recurrences and achievement of pain reduction and complete healing of the lesions. A total of 10 patients with erosive OLP refractory to treatment by corticosteroids were included in the study. All patients were females with a mean age of 48±12years. A complete remission of the disease was achieved after one infiltration of PRGF in 8 patients. Only 2 patients required a total of 2 infiltrations to heal. Hydropic degeneration of the epithelium basal layer, band-like subepithelial lymphocytic infiltration and fibrin deposits in the epithelium were observed in all patients. Interestingly plasma cells were present in 2 patients. All patients presenting plasma cells healed after only one PRGF infiltration. However, 2 patients out of 6 (no plasma cells) required 2 infiltrations. The local administration of autologous local factors could overcome the deficit of biomolecular clues and thus improve cell functions and restore cell-matrix communication. Copyright © 2017 Elsevier GmbH. All rights reserved.

Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors

PubMed Central

Cuervo, Belen; Rubio, Monica; Sopena, Joaquin; Dominguez, Juan Manuel; Vilar, Jose; Morales, Manuel; Cugat, Ramón; Carrillo, Jose Maria

2014-01-01

Purpose: The aim of this study was to compare the efficacy and safety of a single intra-articular injection of adipose mesenchymal stem cells (aMSCs) versus plasma rich in growth factors (PRGF) as a treatment for reducing symptoms in dogs with hip osteoarthritis (OA). Methods: This was a randomized, multicenter, blinded, parallel group. Thirty-nine dogs with symptomatic hip OA were assigned to one of the two groups, to receive aMSCs or PRGF. The primary outcome measures were pain and function subscales, including radiologic assessment, functional limitation and joint mobility. The secondary outcome measures were owners’ satisfaction questionnaire, rescue analgesic requirement and overall safety. Data was collected at baseline, then, 1, 3 and 6 months post-treatment. Results: OA degree did not vary within groups. Functional limitation, range of motion (ROM), owner’s and veterinary investigator visual analogue scale (VAS), and patient’s quality of life improved from the first month up to six months. The aMSCs group obtained better results at 6 months. There were no adverse effects during the study. Our findings show that aMSCs and PRGF are safe and effective in the functional analysis at 1, 3 and 6 months; provide a significant improvement, reducing dog’s pain, and improving physical function. With respect to basal levels for every parameter in patients with hip OA, aMSCs showed better results at 6 months. PMID:25089877

Intradiscal and intra-articular facet infiltrations with plasma rich in growth factors reduce pain in patients with chronic low back pain.

PubMed

Kirchner, Fernando; Anitua, Eduardo

2016-01-01

Low back pain (LBP) is a complex and disabling condition, and its treatment becomes a challenge. The aim of our study was to assess the clinical outcome of plasma rich in growth factors (PRGF-Endoret) infiltrations (one intradiscal, one intra-articular facet, and one transforaminal epidural injection) under fluoroscopic guidance-control in patients with chronic LBP. PRGF-Endoret which has been shown to be an efficient treatment to reduce joint pain. The study was designed as an observational retrospective pilot study. Eighty-six patients with a history of chronic LBP and degenerative disease of the lumbar spine who met inclusion and exclusion criteria were recruited between December 2010 and January 2012. One intradiscal, one intra-articular facet, and one transforaminal epidural injection of PRGF-Endoret under fluoroscopic guidance-control were carried out in 86 patients with chronic LBP in the operating theater setting. Descriptive statistics were performed using absolute and relative frequency distributions for qualitative variables and mean values and standard deviations for quantitative variables. The nonparametric Friedman statistical test was used to determine the possible differences between baseline and different follow-up time points on pain reduction after treatment. Pain assessment was determined using a visual analog scale (VAS) at the first visit before (baseline) and after the procedure at 1, 3, and 6 months. The pain reduction after the PRGF-Endoret injections showed a statistically significant drop from 8.4 ± 1.1 before the treatment to 4 ± 2.6, 1.7 ± 2.3, and 0.8 ± 1.7 at 1, 3, and 6 months after the treatment, respectively, with respect to all the time evaluations ( P < 0.0001) except for the pain reduction between the 3 rd and 6 th month whose signification was lower ( P < 0.05). The analysis of the VAS over time showed that at the end point of the study (6 months), 91% of patients showed an excellent score, 8.1% showed a moderate improvement, and 1.2% were in the inefficient score. Fluoroscopy-guided infiltrations of intervertebral discs and facet joints with PRGF in patients with chronic LBP resulted in significant pain reduction assessed by VAS.

Intradiscal and intra-articular facet infiltrations with plasma rich in growth factors reduce pain in patients with chronic low back pain

PubMed Central

Kirchner, Fernando; Anitua, Eduardo

2016-01-01

Context: Low back pain (LBP) is a complex and disabling condition, and its treatment becomes a challenge. Aims: The aim of our study was to assess the clinical outcome of plasma rich in growth factors (PRGF-Endoret) infiltrations (one intradiscal, one intra-articular facet, and one transforaminal epidural injection) under fluoroscopic guidance-control in patients with chronic LBP. PRGF-Endoret which has been shown to be an efficient treatment to reduce joint pain. Settings and Design: The study was designed as an observational retrospective pilot study. Eighty-six patients with a history of chronic LBP and degenerative disease of the lumbar spine who met inclusion and exclusion criteria were recruited between December 2010 and January 2012. Subjects and Methods: One intradiscal, one intra-articular facet, and one transforaminal epidural injection of PRGF-Endoret under fluoroscopic guidance-control were carried out in 86 patients with chronic LBP in the operating theater setting. Statistical Analysis Used: Descriptive statistics were performed using absolute and relative frequency distributions for qualitative variables and mean values and standard deviations for quantitative variables. The nonparametric Friedman statistical test was used to determine the possible differences between baseline and different follow-up time points on pain reduction after treatment. Results: Pain assessment was determined using a visual analog scale (VAS) at the first visit before (baseline) and after the procedure at 1, 3, and 6 months. The pain reduction after the PRGF-Endoret injections showed a statistically significant drop from 8.4 ± 1.1 before the treatment to 4 ± 2.6, 1.7 ± 2.3, and 0.8 ± 1.7 at 1, 3, and 6 months after the treatment, respectively, with respect to all the time evaluations (P < 0.0001) except for the pain reduction between the 3rd and 6th month whose signification was lower (P < 0.05). The analysis of the VAS over time showed that at the end point of the study (6 months), 91% of patients showed an excellent score, 8.1% showed a moderate improvement, and 1.2% were in the inefficient score. Conclusions: Fluoroscopy-guided infiltrations of intervertebral discs and facet joints with PRGF in patients with chronic LBP resulted in significant pain reduction assessed by VAS. PMID:27891035

Radiographic evaluation of bone regeneration after the application of plasma rich in growth factors in a lower third molar socket: a case report

PubMed Central

2009-01-01

A 42-year-old Mediterranean male presented complaining of inability to sustain good oral care at the posterior aspect of the lower right jaw. The main problems were food impaction in the area and the subsequent malodor. The patient reported remarkable medical history. Clinical examination revealed local erytherma with noticeable bone defect distal to the second molar with obvious defect in the mesial wall of the third molar; the penetration depth was found to be up to 6 mm. Radiological evaluation confirmed the defect and it was attributed to the mesioangularly partially impacted lower third molar. It was decided that third molar should be extracted and concentrate of the patient's growth factors (PRGF) to be applied into the bony defect to stimulate bone regeneration and promote healing. The third molar tooth was, then, removed surgically and the PRGF, which was prepared preoperatively, was implanted in the socket. At the first postoperative day, moderate pain was the main complaint and was controlled by NSAIDs. One week postoperatively, the sutures were removed and there was good tissue healing on examination. On the fiftieth postoperative day, radiographic evaluation took place and showed noticeable enhancement of density and radio-opacity in the third molar socket area, in comparison with the baseline image. Further, clinical examination showed significant reduction of periodontal pocketing and evidence of new bone formation. In conclusion, PRGF was very successful in stimulating bone regeneration and promote healing following dental extraction. PMID:20062651

Subconjunctival PRGF Fibrin Membrane as an Adjuvant to Nonpenetrating Deep Sclerectomy: A 2-Year Pilot Study.

PubMed

Rodríguez-Agirretxe, Iñaki; Freire, Vanesa; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo; Díez-Feijóo, Elio; Acera, Arantxa

2018-01-01

To evaluate the potential role of the autologous PRGF (plasma rich in growth factors) fibrin membrane in tissue regeneration after glaucoma filtering surgery. Ten patients with medically uncontrolled primary open-angle glaucoma underwent nonpenetrating deep sclerectomy and were treated with PRGF fibrin membrane as adjuvant. Intraocular pressure reduction was the primary outcome. This variable was measured preoperatively and also at each follow-up visit. Secondary outcomes included the number of antiglaucoma medications, anterior segment optical coherence tomography bleb examination, photographic bleb evaluation, and subjective clinical symptomatology evaluation. The surgical technique showed a significant reduction (p < 0.05) in intraocular pressure in relation to preoperative values at each time of the study, decreasing from 23.3 ± 6.4 to 15.2 ± 4.6 mm Hg at 2 years. Furthermore, the number of antiglaucoma medications consumed showed a significant reduction at the end point of the study compared with the preoperative situation. Optical coherence tomography and photographic filtering bleb variables experienced a progressive reduction during the follow-up. Subjective symptoms showed a reduction from 8.3 ± 4.5 to 4.2 ± 5.3 at 2 years. PRGF-Endoret treatment could promote ocular surface regeneration after glaucoma surgery, enhancing the surgery success rates and reducing the need for postoperative medications. It is important to highlight that this is a preliminary study and some large clinical studies are necessary to verify these results. © 2017 S. Karger AG, Basel.

[Conservative treatment using plasma rich in growth factors (PRGF) for injury to the ligamentous complex of the ankle].

PubMed

Frei, R; Biosca, F E; Handl, M; Trc, T

2008-02-01

The authors describe the therapeutic utilization of separated/isolated autologous growth factors in semiconservative treatment of type III injury to the ankle ligamentous complex. Between October 2004 and March 2005 a group of 11 patients, two women and nine men, aged 18 to 41 (average, 25.09) years with acute injury to the lateral ligamentous complex of the ankle were treated by plasma rich in growth factors (PRGF) infiltration. On functional radiographic examination, the post-traumatic lateral opening of the tibiotalar intraarticular space was 17.45 degrees (range, 12.0-30.0; s = 5.68). The injured patients were clinically examined and standard forced inversion radiographs were made using topical anesthesia. Autologous PRGF activated with calcium chloride was used to infiltrate the injured tissues. The treatment was followed by immobilization of the joint and its subsequent rehabilitation. Clinical examination of injured tissues was carried out at 4 and 6 weeks of follow-up, using stability assessment tests and functional radiography of the ankle. Physical therapy included standard procedures, but faster regeneration of the soft tissues allowed for more exercises. The average time of healing was 5.18 weeks. Five patients showed no signs of instability at 4 weeks after therapy and could return to their previous sports activities. One patient had lateral ankle instability at 5 weeks and therefore the therapy continued with prolonged immobilization and then rehabilitation at a slower pace. The average lateral opening of the tibiotalar intra-articular space at 4 or 6 follow-up weeks was 4.73 degrees (range, 3.0 - 7.0; s = 1.19). At 6 weeks after therapy, 90.9% of the patients resumed their full sports activities. Ankle distortion with swelling, hematoma and pain, but with no radiographic findings of ligament lesions, is usually treated conservatively by ankle immobilization and early rehabilitation. When an injury to the fibular ankle ligaments occurs (i.e., opening of the tibiotalar intra-articular space laterally by more than 10 degrees), surgery and reconstruction of the injured tissues is indicated. An alternative treatment of acute injury to the ligamentous ankle complex includes application of growth factors into the injured tissues. The presence of growth factors facilitates the healing and remodeling of soft tissues and regenaration may begin before leukocytes infiltrate the affected site. At a relatively low level of interleukins, the inflammatory phase of healing is suppressed, pain is reduced and the process of reparation and regenaration is accelerated. The use of bioinductive properties of growth factors is one of the options for treating injuries to the ligamentous complex of the ankle. It can be used alternatively to conventional surgery or as an adjunct accelerating and improving the healing of traumatic lesions and postoperative conditions.

High-throughput proteomic characterization of plasma rich in growth factors (PRGF-Endoret)-derived fibrin clot interactome.

PubMed

Anitua, Eduardo; Prado, Roberto; Azkargorta, Mikel; Rodriguez-Suárez, Eva; Iloro, Ibon; Casado-Vela, Juan; Elortza, Felix; Orive, Gorka

2015-11-01

Plasma rich in growth factors (PRGF®-Endoret®) is an autologous technology that contains a set of proteins specifically addressed to wound healing and tissue regeneration. The scaffold formed by using this technology is a clot mainly composed of fibrin protein, forming a three-dimensional (3D) macroscopic network. This biomaterial is easily obtained by biotechnological means from blood and can be used in a range of situations to help wound healing and tissue regeneration. Although the main constituent of this clot is the fibrin scaffold, little is known about other proteins interacting in this clot that may act as adjuvants in the healing process. The aim of this study was to characterize the proteins enclosed by PRGF-Endoret scaffold, using a double-proteomic approach that combines 1D-SDS-PAGE approach followed by LC-MS/MS, and 2-DE followed by MALDI-TOF/TOF. The results presented here provide a description of the catalogue of key proteins in close contact with the fibrin scaffold. The obtained lists of proteins were grouped into families and networks according to gene ontology. Taken together, an enrichment of both proteins and protein families specifically involved in tissue regeneration and wound healing has been found. Copyright © 2013 John Wiley & Sons, Ltd.

Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial.

PubMed

Vaquerizo, Víctor; Plasencia, Miguel Ángel; Arribas, Ignacio; Seijas, Roberto; Padilla, Sabino; Orive, Gorka; Anitua, Eduardo

2013-10-01

The purpose of this study was to compare the efficacy and safety in a randomized, clinical trial of 3 injections of PRGF-Endoret (BTI Biotechnology Institute, Vitoria, Spain) versus one single intra-articular injection of Durolane hyaluronic acid (HA) (Q-MED AB, Uppsala, Sweden) as a treatment for reducing symptoms in patients with knee osteoarthritis (OA). Ninety-six patients with symptomatic knee OA were randomly assigned to receive PRGF-Endoret (3 injections on a weekly basis) or one infiltration with Durolane HA. The primary outcome measures were a 30% decrease and a 50% decrease in the summed score for the pain, physical function, and stiffness subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne scores from baseline to weeks 24 and 48. The percentage of OMERACT-OARSI (Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative) responders was also documented. As secondary outcomes, pain, stiffness, and physical function by use of the WOMAC and the Lequesne score were considered and overall safety of the injection themselves. The mean age of the patients was 63.6 years. Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA. The rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including pain, stiffness, and physical function on the WOMAC, Lequesne index, and OMERACT-OARSI responders at 24 and 48 weeks. Adverse events were mild and evenly distributed between the groups. Our findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks; provides a significant clinical improvement, reducing patients' pain and improving joint stiffness and physical function with respect to basal levels in patients with knee OA; and should be considered in the treatment of patients with knee OA. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Intranasal delivery of plasma and platelet growth factors using PRGF-Endoret system enhances neurogenesis in a mouse model of Alzheimer's disease.

PubMed

Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Antequera, Desiree; Padilla, Sabino; Orive, Gorka; Carro, Eva

2013-01-01

Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer's disease (AD) induced by a combination of toxic amyloid-β peptide (Aβ) and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret), an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD.

Intranasal Delivery of Plasma and Platelet Growth Factors Using PRGF-Endoret System Enhances Neurogenesis in a Mouse Model of Alzheimer’s Disease

PubMed Central

Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Antequera, Desiree; Padilla, Sabino; Orive, Gorka; Carro, Eva

2013-01-01

Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer’s disease (AD) induced by a combination of toxic amyloid-β peptide (Aβ) and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret), an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD. PMID:24069173

Soft Tissue Repair with Easy-Accessible Autologous Newborn Placenta or Umbilical Cord Blood in Severe Malformations: A Primary Evaluation

PubMed Central

2017-01-01

Disrupted organogenesis leads to permanent malformations that may require surgical correction. Autologous tissue grafts may be needed in severe lack of orthotopic tissue but include donor site morbidity. The placenta is commonly discarded after birth and has a therapeutic potential. The aim of this study was to determine if the amnion from placenta or plasma rich of growth factors (PRGF) with mononuclear cells (MNC) from umbilical cord blood (UCB), collected noninvasively, could be used as bio-constructs for autologous transplantation as an easy-accessible no cell culture-required method. Human amnion and PRGF gel were isolated and kept in culture for up to 21 days with or without small intestine submucosa (SIS). The cells in the constructs showed a robust phenotype without induced increased proliferation (Ki67) or apoptosis (caspase 3), but the constructs showed decreased integrity of the amnion-epithelial layer at the end of culture. Amnion-residing cells in the SIS constructs expressed CD73 or pan-cytokeratin, and cells in the PRGF-SIS constructs expressed CD45 and CD34. This study shows that amnion and UCB are potential sources for production of autologous grafts in the correction of congenital soft tissue defects. The constructs can be made promptly after birth with minimal handling or cell expansion needed. PMID:29403534

Evaluation of implant osseointegration with different regeneration techniques in the treatment of bone defects around implants: an experimental study in a rabbit model.

PubMed

Guerra, Isabel; Morais Branco, Fernando; Vasconcelos, Mário; Afonso, Américo; Figueiral, Helena; Zita, Raquel

2011-03-01

The aim of this study was to evaluate the osseointegration of implants placed in areas with artificially created bone defects, using three bone regeneration techniques. The experimental model was the rabbit femur (16), where bone defects were created and implants were placed. The peri-implant bone defects were filled with a deproteinized bovine bone mineral, NuOss™ (N), NuOss™ combined with plasma rich in growth factors (PRGF) (N+PRGF), NuOss™ covered by an RCM(6) membrane (N+M), or remained unfilled (control group [C]). After 4 and 8 weeks, the animals were euthanized and bone tissue blocks with the implants and the surrounding bone tissue were removed and processed according to a histological protocol for hard tissues on non-decalcified ground sections. The samples were studied by light and electron scanning microscopy, histometric analysis was performed to assess the percentage of bone in direct contact with the implant surface and a statistical analysis of the results was performed. In the samples analyzed 4 weeks after implantation, the percentage of bone tissue in direct contact with the implant surface for the four groups were 57.66±24.39% (N), 58.62±20.37% (N+PRGF), 70.82±20.34 % (N+M) and 33.07±5.49% (C). In the samples with 8 weeks of implantation time, the percentage of bone in direct contact was 63.35±27.69% (N), 58.42±24.77% (N+PRGF), 78.02±15.13% (N+M) and 40.28±27.32% (C). In terms of the percentage of bone contact, groups N and N+M presented statistically significant differences from group C in the 4-week trial test (P<0.05; ANOVA). For the 8-week results, only group N+M showed statistically significant differences when compared with group C (P<0.05; ANOVA). In conclusion, the NuOss™ granules/RCM(6) membrane combination presented a percentage of bone contact with the implant surface statistically greater than in the other groups. © 2010 John Wiley & Sons A/S.

The potential impact of the preparation rich in growth factors (PRGF) in different medical fields.

PubMed

Anitua, Eduardo; Sánchez, Mikel; Orive, Gorka; Andía, Isabel

2007-11-01

Platelet-rich preparations constitute a relatively new biotechnology for the stimulation and acceleration of tissue healing and bone regeneration. The versatility and biocompatibility of this approach has stimulated its therapeutic use in numerous medical and scientific fields including dentistry, oral implantology, orthopaedics, ulcer treatment, tissue engineering among others. Here we discuss the important progress that has been accomplished in the field of platelet-rich preparations in the last few years. Some of the most interesting therapeutic applications of this technology are discussed as are some of the limitations, future challenges and directions in the field.

Impact of the use of plasma rich in growth factors (PRGF) on the quality of life of patients treated with endodontic surgery when a perforation of sinus membrane occurred. A comparative study.

PubMed

Taschieri, S; Corbella, S; Tsesis, I; Del Fabbro, M

2014-03-01

The aim of this retrospective investigation was to evaluate the postoperative quality of life after endodontic surgery in maxillary molars when a sinus membrane perforation occurred and platelet concentrates were used. Included patients were treated by microsurgical endodontic treatment in molar and premolar maxillary regions between 2007 and 2010. Patients who fulfilled the inclusion criteria were screened. Data from the quality of life questionnaire were analyzed. The use of plasma rich in growth factors (PRGF) (test group) was compared with a control group when a Schneiderian membrane perforation occurred during endodontic surgery performed with a modern technique in maxillary molars and premolars. A total of 20 patients (12 in the control group and eight in the test group) fulfilled the inclusion criteria. No differences were evaluated at baseline for clinical parameters. Significantly improved patients' quality of life was observed in the test group considering symptoms as swelling, bad breath or taste, and pain. Functional activities were less impaired in the test group and swelling was significantly higher in the control group. In the test group, pain was significantly lower than the control group during the first 6 days after surgery and also, the consumption of painkillers was lower for patients belonging to the test group even if it was not statistically significant. In general, a small sinus membrane perforation (less than 6 mm) during endodontic surgery did not cause severe complications. The use of platelet concentrates could be effective in reducing the impact on patients' quality of life, decreasing pain and surgery side effects as well as swelling.

Comparison of the Mechanical Properties of Early Leukocyte- and Platelet-Rich Fibrin versus PRGF/Endoret Membranes.

PubMed

Khorshidi, Hooman; Raoofi, Saeed; Bagheri, Rafat; Banihashemi, Hodasadat

2016-01-01

Objectives. The mechanical properties of membranes are important factors in the success of treatment and clinical handling. The goal of this study was to compare the mechanical properties of early leukocyte- and platelet-rich fibrin (L-PRF) versus PRGF/Endoret membrane. Materials and Methods. In this experimental study, membranes were obtained from 10 healthy male volunteers. After obtaining 20 cc venous blood from each volunteer, 10 cc was used to prepare early L-PRF (group 1) and the rest was used to get a membrane by PRGF-Endoret system (group 2). Tensile loads were applied to specimens using universal testing machine. Tensile strength, stiffness, and toughness of the two groups of membranes were calculated and compared by paired t-test. Results. The mean tensile strength and toughness were higher in group 1 with a significant difference (P < 0.05). The mean stiffness in group 1 was also higher but not statistically significant (P > 0.05). Conclusions. The results showed that early L-PRF membranes had stronger mechanical properties than membranes produced by PRGF-Endoret system. Early L-PRF membranes might have easier clinical handling and could be a more proper scaffold in periodontal regenerative procedures. The real results of the current L-PRF should be in fact much higher than what is reported here.

Comparison of the Mechanical Properties of Early Leukocyte- and Platelet-Rich Fibrin versus PRGF/Endoret Membranes

PubMed Central

Khorshidi, Hooman; Raoofi, Saeed; Bagheri, Rafat; Banihashemi, Hodasadat

2016-01-01

Objectives. The mechanical properties of membranes are important factors in the success of treatment and clinical handling. The goal of this study was to compare the mechanical properties of early leukocyte- and platelet-rich fibrin (L-PRF) versus PRGF/Endoret membrane. Materials and Methods. In this experimental study, membranes were obtained from 10 healthy male volunteers. After obtaining 20 cc venous blood from each volunteer, 10 cc was used to prepare early L-PRF (group 1) and the rest was used to get a membrane by PRGF-Endoret system (group 2). Tensile loads were applied to specimens using universal testing machine. Tensile strength, stiffness, and toughness of the two groups of membranes were calculated and compared by paired t-test. Results. The mean tensile strength and toughness were higher in group 1 with a significant difference (P < 0.05). The mean stiffness in group 1 was also higher but not statistically significant (P > 0.05). Conclusions. The results showed that early L-PRF membranes had stronger mechanical properties than membranes produced by PRGF-Endoret system. Early L-PRF membranes might have easier clinical handling and could be a more proper scaffold in periodontal regenerative procedures. The real results of the current L-PRF should be in fact much higher than what is reported here. PMID:26880919

Pain in donor site after BTB-ACL reconstruction with PRGF: a randomized trial.

PubMed

Seijas, Roberto; Cuscó, Xavier; Sallent, Andrea; Serra, Iván; Ares, Oscar; Cugat, Ramón

2016-06-01

Anterior cruciate ligament (ACL) tears are highly incident injuries in young athletes within our work area. The use of the patellar graft, despite being the treatment of choice, presents post-operative problems such as anterior knee pain, which limits its use and leads to preference being taken for alternative grafts. Our aim was to evaluate if the application of PRGF reduces anterior knee pain in donor site in BTB-ACL reconstruction. 43 patients were included in the double-blinded and randomized clinical trial comparing two patient groups who underwent ACL reconstruction using patellar tendon graft, comparing anterior knee pain with and without the application of PRGF at the donor site after harvesting the graft. The PRGF group showed decreased donor site pain in comparison to the control group, with significant differences in the first two months of follow-up. The application of PRGF decreased donor site pain compared to the control group.

Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

PubMed

Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

2013-10-01

Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma. Copyright © 2013 Elsevier GmbH. All rights reserved.

A Preliminary Evaluation of Lyophilized Gelatin Sponges, Enhanced with Platelet-Rich Plasma, Hydroxyapatite and Chitin Whiskers for Bone Regeneration

PubMed Central

Rodriguez, Isaac A.; Sell, Scott A.; McCool, Jennifer M.; Saxena, Gunjan; Spence, Andrew J.; Bowlin, Gary L.

2013-01-01

The purpose of this study was to perform a number of preliminary in vitro evaluations on an array of modified gelatin gel sponge scaffolds for use in a bone graft application. The gelatin gels were modified through the addition of a number of components which each possess unique properties conducive to the creation and regeneration of bone: a preparation rich in growth factors (PRGF, a bioactive, lyophilized form of platelet-rich plasma), hydroxyapatite, and chitin whiskers. Platelet-rich plasma therapy is an emerging practice that has proven effective in a number of clinical applications, including enhancing bone repair through improved deposition of new bony matrix and angiogenesis. As such, the inclusion of PRGF in our gelatin scaffolds was intended to significantly enhance scaffold bioactivity, while the addition of hydroxyapatite and chitin whiskers were anticipated to increase scaffold strength. Additionally, the gelatin sponges, which readily dissolve in aqueous solutions, were subjected to 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linking, either during or post-gelation, to control their rate of degradation. Scaffolds were evaluated in vitro with respect to compressive strength, mass loss/degradation, protein release, and cellular interaction, with results demonstrating the potential of the gelatin gel sponge scaffold for use in the regeneration of bone. PMID:24709699

Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

PubMed

Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

2016-12-01

The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

An overview of platelet products (PRP, PRGF, PRF, etc.) in the Iranian studies.

PubMed

Raeissadat, Seyed Ahmad; Babaee, Marzieh; Rayegani, Seyed Mansour; Hashemi, Zahra; Hamidieh, Amir Ali; Mojgani, Parviz; Fouladi Vanda, Hossein

2017-11-01

The aim of the study was to carry out a review of published studies on various platelet products in Iranian studies. Electronic databases were searched for relevant articles. Two review authors independently extracted data via a tested extraction sheet, and disagreements were resolved by a meeting with a third review author. Bone disorders (25%), wound and fistula (16%), dental and gingival disorders (14%) and osteoarthritis (11%) have more relative frequency based on different fields. The necessity of pursuing standard protocols in the preparation of platelet products, stating the precise content of platelets and growth factors, and long-term follow-up of study subjects were the most important points in Iranian studies.

Investigation of Peri-Implant Bone Healing Using Autologous Plasma Rich in Growth Factors in the Canine Mandible After 12 Weeks: A Pilot Study

PubMed Central

Birang, Reza; Tavakoli, Mohammad; Shahabouei, Mohammad; Torabi, Alireza; Dargahi, Ali; Soolari, Ahmad

2011-01-01

Introduction: Faster reconstruction of patients’ masticatory systems is the aim of modern dentistry. A number of studies have indicated that application of growth factors to the surface of a dental implant leads to accelerated and enhanced osseointegration. The objective of the present study was to investigate the effect of plasma rich in growth factors on peri-implant bone healing. Materials and Methods: For the purpose of this study, two healthy, mixed-breed canines were selected, and the premolars were extracted from both sides of the mandible. Three months after premolar removal, 12 implants, each 5 mm in diameter and 10 mm in length, were placed in osteotomy sites on both sides of the mandible. Prior to placement, plasma rich in growth factors was applied to the surfaces of six implants, while the other six were used without plasma rich in growth factors. The implants were removed after 12 weeks along with the bone surrounding the sites using a trephine bur. One mesiodistal section containing the surrounding bone from each implant block, 50 µm in diameter, was prepared for histologic and histomorphometric investigation with an optical microscope. Results: The sites with implants treated with plasma rich in growth factors showed more bone-to-implant contact compared to control sites. Also, higher values for bone trabecular thickness and bone maturity were recorded for the PRGF-treated sites than for the control sites. Conclusion: Application of plasma rich in growth factors to the surface of an implant may enhance the bone healing process as well as bone-to-implant contact, thereby helping to achieve faster osseointegration. PMID:22145011

An overview of platelet products (PRP, PRGF, PRF, etc.) in the Iranian studies

PubMed Central

Raeissadat, Seyed Ahmad; Babaee, Marzieh; Rayegani, Seyed Mansour; Hashemi, Zahra; Hamidieh, Amir Ali; Mojgani, Parviz; Fouladi Vanda, Hossein

2017-01-01

Aim: The aim of the study was to carry out a review of published studies on various platelet products in Iranian studies. Materials & methods: Electronic databases were searched for relevant articles. Two review authors independently extracted data via a tested extraction sheet, and disagreements were resolved by a meeting with a third review author. Results: Bone disorders (25%), wound and fistula (16%), dental and gingival disorders (14%) and osteoarthritis (11%) have more relative frequency based on different fields. Conclusion: The necessity of pursuing standard protocols in the preparation of platelet products, stating the precise content of platelets and growth factors, and long-term follow-up of study subjects were the most important points in Iranian studies. PMID:29134118

Comparison between PRP, PRGF and PRF: lights and shadows in three similar but different protocols.

PubMed

Giannini, S; Cielo, A; Bonanome, L; Rastelli, C; Derla, C; Corpaci, F; Falisi, G

2015-01-01

The main goal of the modern surgery is to get a low invasiveness and a high rate of clinical healing: in the last years, it has been introduced the concept of a "regenerative surgery", and many techniques has been widely described in the literature. The most used are PRP, PRGF and PRF techniques. Aim of this research is to compare the three protocol of PRP, PRF and PRGF in their essential features, so to suggest to the practitioners the best blood product to use in the regenerative surgery. Among the advantages that shows the PRF, compared to PRP and PRGF, we can cite a greater simplicity of production for the absence of manipulation that leads to a reduced possibility of alteration of the protocol due to an error of the operator. The special texture of the PRF and its biological features shows clearly an interesting surgical versatility and all the characteristics that can support a faster tissues regeneration and high-quality clinical outcomes.

Platelet-Rich Plasma Favors Proliferation of Canine Adipose-Derived Mesenchymal Stem Cells in Methacrylate-Endcapped Caprolactone Porous Scaffold Niches

PubMed Central

Rodríguez-Jiménez, Francisco Javier; Valdes-Sánchez, Teresa; Carrillo, José M.; Rubio, Mónica; Monleon-Prades, Manuel; García-Cruz, Dunia Mercedes; García, Montserrat; Cugat, Ramón; Moreno-Manzano, Victoria

2012-01-01

Osteoarticular pathologies very often require an implementation therapy to favor regeneration processes of bone, cartilage and/or tendons. Clinical approaches performed on osteoarticular complications in dogs constitute an ideal model for human clinical translational applications. The adipose-derived mesenchymal stem cells (ASCs) have already been used to accelerate and facilitate the regenerative process. ASCs can be maintained in vitro and they can be differentiated to osteocytes or chondrocytes offering a good tool for cell replacement therapies in human and veterinary medicine. Although ACSs can be easily obtained from adipose tissue, the amplification process is usually performed by a time consuming process of successive passages. In this work, we use canine ASCs obtained by using a Bioreactor device under GMP cell culture conditions that produces a minimum of 30 million cells within 2 weeks. This method provides a rapid and aseptic method for production of sufficient stem cells with potential further use in clinical applications. We show that plasma rich in growth factors (PRGF) treatment positively contributes to viability and proliferation of canine ASCs into caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) scaffolds. This biomaterial does not need additional modifications for cASCs attachment and proliferation. Here we propose a framework based on a combination of approaches that may contribute to increase the therapeutical capability of stem cells by the use of PRGF and compatible biomaterials for bone and connective tissue regeneration. PMID:24955632

The role of soluble and insoluble gastric fluid components in the pathogenesis of obliterative bronchiolitis in rat lung allografts.

PubMed

Leung, Jason H; Chang, Jui-Chih; Bell, Sadé M; Holzknecht, Zoie E; Thomas, Samantha M; Everett, Mary Lou; Parker, William; Davis, R Duane; Lin, Shu S

2016-02-01

Repetitive gastric fluid aspirations have been shown to lead to obliterans bronchiolitis (OB), but the component or components of gastric fluid that are responsible are unknown. This study investigates the role of particulates and, separately, soluble material in gastric fluid during the development of OB. Whole gastric fluid (WGF) was collected from male Fischer 344 (F344) rats and separated by centrifugation into particle reduced gastric fluid (PRGF) and particulate components resuspended in normal saline (PNS). Orthotopic left lung transplants from male Wistar-Kyoto rats into F344 rats were performed using a modification of the nonsuture external cuff technique with prolonged cold ischemia. Rats were subjected to weekly aspiration of 0.5 ml/kg of WGF (n = 9), PRGF (n = 10), PNS (n = 9), or normal saline (control, NS; n = 9) for 8 weeks following transplantation. Lung allografts treated with WGF, PRGF, or PNS developed a significantly greater percentage of OB-like lesions compared with the control. No statistical difference was observed when comparing the fibrosis grades or the percentage of OB lesions of WGF, PRGF, and PNS groups, suggesting that both soluble and insoluble components of gastric fluid can promote the development of aspiration-induced OB and fibrosis in lung allografts. © 2015 Steunstichting ESOT.

Platelet-rich plasma and platelet gel preparation using Plateltex.

PubMed

Mazzucco, L; Balbo, V; Cattana, E; Borzini, P

2008-04-01

The platelet gel is made by embedding concentrate platelets within a semisolid (gel) network of polymerized fibrin. It is believed that this blood component will be used more and more in the treatment of several clinical conditions and as an adjunctive material in tissue engineering. Several systems are available to produce platelet-rich plasma (PRP) for topical therapy. Recently, a new system became commercially available, Plateltex. Here we report the technical performance of this system in comparison with the performance of other commercially available systems: PRGF, PRP-Landesber, Curasan, PCCS, Harvest, Vivostat, Regen and Fibrinet. Both the PRP and the gel were prepared according to the manufacturer's directions. The blood samples of 20 donors were used. The yield, the efficiency, and the amount of platelet-derived growth factor AB (PDGF-AB), transforming growth factor beta, vascular endothelial growth factor and fibroblast growth factor were measured in the resulting PRP. The feature of the batroxobin-induced gelation was evaluated. The yield, the collection efficiency and the growth factor content of Plateltex were comparable to those of most of the other available systems. The gelation time was not dependent on the fibrinogen concentration; however, it was strongly influenced by the contact surface area of the container where the clotting reaction took place (P < 0.0001). Plateltex provided platelet recovery, collection efficiency and PDGF-AB availability close to those provided by other systems marketed with the same intended use. Batroxobin, the enzyme provided to induce gelation, acts differently from thrombin, which is used by most other systems. Platelets treated with thrombin become activated; they release their growth factors quickly. Furthermore, thrombin-platelet interaction is a physiological mechanism that hastens the clot-retraction rate. On the contrary, platelets treated with batroxobin do not become activated; they are passively entrapped within the fibrin network, and their growth factor release occurs slowly. In these conditions, the clot retraction takes longer to occur. According to these differences between thrombin and batroxobin, it is expected that batroxobin-induced PRP activation will tailor slow release of the platelet content, thus, providing longer in loco availability of trophic factors. In selected clinical conditions, this durable anabolic factor availability might be preferable to quick thrombin-induced growth factor release.

Leukocyte Inclusion within a Platelet Rich Plasma-Derived Fibrin Scaffold Stimulates a More Pro-Inflammatory Environment and Alters Fibrin Properties

PubMed Central

Anitua, Eduardo; Zalduendo, Mar; Troya, María; Padilla, Sabino; Orive, Gorka

2015-01-01

One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions. PMID:25823008

Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

NASA Astrophysics Data System (ADS)

Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

2016-09-01

The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

Comparison between two different platelet-rich plasma preparations and control applied during anterior cruciate ligament reconstruction. Is there any evidence to support their use?

PubMed

Valentí Azcárate, Andrés; Lamo-Espinosa, Jose; Aquerreta Beola, Jesús Dámaso; Hernandez Gonzalez, Milagros; Mora Gasque, Gonzalo; Valentí Nin, Juan Ramón

2014-10-01

To compare the clinical, analytical and graft maturation effects of two different platelet-rich plasma (PRP) preparations applied during anterior cruciate ligament (ACL) reconstruction. A total of 150 patients with ACL disruption were included in the study. Arthroscopic ACL reconstruction with patellar tendon allograft was conducted on all knees using the same protocol. One hundred patients were prospectively randomised to either a group to receive double-spinning platelet-enriched gel (PRP) with leukocytes (n=50) or to a non-gel group (n=50). Finally, we included 50 patients treated with a platelet-rich preparation from a single-spinning procedure (PRGF Endoret(®) Technology) without leukocytes. Inflammatory parameters, including C-reactive protein (CRP) and knee perimeters (PER), were measured 24 hours and 10 days after surgery. Postoperative pain score (visual analogue score [VAS]) was recorded the day after surgery. Follow-up visits occurred postoperatively at 3, 6, and 12 months. The International Knee Documentation Committee scale (IKDC) was included to compare functional state, and MRI was conducted 6 months after surgery. The PRGF group showed a statistically significant improvement in swelling and inflammatory parameters compared with the other two groups at 24 hours after surgery (p<0.05). The results did not show any significant differences between groups for MRI and clinical scores. PRGF used in ACL allograft reconstruction was associated with reduced swelling; however, the intensity and uniformity of the graft on MRI were similar in the three groups, and there was no clinical or pain improvement compared with the control group. II.

Erythrocyte sedimentation rate and fibrinogen concentration of whole blood influences the cellular composition of platelet-rich plasma obtained from centrifugation methods.

PubMed

Yin, Wenjing; Xu, Zhengliang; Sheng, Jiagen; Xie, Xuetao; Zhang, Changqing

2017-09-01

Erythrocyte sedimentation rate (ESR), which reflects the sedimentation rate of platelets, leukocytes and erythrocytes in response to centrifugal force, may influence the cellular composition of platelet-rich plasma (PRP) obtained via centrifugation methods. However, no relevant studies have substantiated this. In the present study, blood was collected from 40 healthy volunteers and used to prepare PRP with two plasma-based preparation systems [YinPRP and Plasma Rich in Growth Factor (PRGF) systems] and two buffy coat-based systems (RegenPRP and WEGOPRP systems) in a single-donor model. Volumes of PRP and platelet-poor plasma (PPP) that were removed in the preparation process were recorded. Analyses of ESR, haematocrit, C-reaction protein, coagulation, serum glucose and serum lipid of the whole blood used for PRP preparation were performed to evaluate the levels of ESR and the factors known to influence it. Whole blood analysis was performed to evaluate the cellular composition of PRP. Results demonstrated that there were marked positive correlations between the ESR of the whole blood used for PRP preparation and PPP removal efficiencies, platelet concentrations, platelet capture efficiencies and platelet enrichment factors of PRP formulations obtained from plasma-based systems, and PRP yield efficiency of RegenPRP and PPP removal efficiency of WEGOPRP. Furthermore, there were marked negative correlations between ESR and concentrations and enrichment factors of platelets, leukocytes and erythrocytes of RegenPRP. Fibrinogen concentration of the whole blood, which had a marked positive correlation with ESR, also influenced the cellular composition of PRP. These findings may increase the understanding of PRP preparation and provide substantial evidence for the individualised optimisation of PRP preparation systems used in clinical practice.

Clinical evaluation of split-crest technique with ultrasonic bone surgery for narrow ridge expansion: status of soft and hard tissues and implant success.

PubMed

Anitua, Eduardo; Begoña, Leire; Orive, Gorka

2013-04-01

The aim of this study was to evaluate the split-crest technique with ultrasonic bone surgery for implant placement in patients with narrow ridges, focusing on the status of soft and hard tissues and on implant success rate, at least 6 months after implant loading. During September 2007 and November 2008, 15 patients received 37 implants (BTI implants) with split-crest surgical procedure using ultrasonic bone surgery. Plasma rich in growth factors (PRGF®) was applied during split crest procedure to promote tissue regeneration. Implant surfaces were humidified with PRGF to accelerate osseointegration. Patients were recalled for a final clinical evaluation at least 6 months after implant loading. Clinical assessment included the status of soft and hard tissues around implants, and implants' success rate. Thirty-seven implants in 15 patients were evaluated between July 2009 and January 2010. The status of soft tissues was very good, showing adequate plaque index, bleeding index, and probing depth values. Success rate of implants at the end of follow-up (between 11 and 28 months after insertion) was 100%. Bone ridge was measured and compared at final examination showing a mean ridge expansion of 3.35 mm (SD: 0.34). Split-crest with ultrasonic bone surgery can be considered an effective and safe procedure for narrow ridge expansion. © 2011 Wiley Periodicals, Inc.

In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes.

PubMed

Dohan Ehrenfest, David M; Bielecki, Tomasz; Mishra, Allan; Borzini, Piero; Inchingolo, Francesco; Sammartino, Gilberto; Rasmusson, Lars; Everts, Peter A

2012-06-01

In the field of platelet concentrates for surgical use, most products are termed Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and incomplete, leading to many confusions in the scientific database. In this article, a panel of experts discusses this issue and proposes an accurate and simple terminology system for platelet concentrates for surgical use. Four main categories of products can be easily defined, depending on their leukocyte content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; Leukocyteand Platelet-Rich Plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Choukroun's PRF. P-PRP and L-PRP refer to the unactivated liquid form of these products, their activated versions being respectively named P-PRP gels and L-PRP gels. The purpose of this search for a terminology consensus is to plead for a more serious characterization of these products. Researchers have to be aware of the complex nature of these living biomaterials, in order to avoid misunderstandings and erroneous conclusions. Understanding the biomaterials or believing in the magic of growth factors ? From this choice depends the future of the field.

Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial.

PubMed

Laver, Lior; Carmont, Michael R; McConkey, Mark O; Palmanovich, Ezequiel; Yaacobi, Eyal; Mann, Gideon; Nyska, Meir; Kots, Eugene; Mei-Dan, Omer

2015-11-01

Syndesmotic sprains are uncommon injuries that require prolonged recovery. The influence of ultrasound-guided injections of platelet-rich plasma (PRP) into the injured antero-inferior tibio-fibular ligaments (AITFL) in athletes on return to play (RTP) and dynamic stability was studied. Sixteen elite athletes with AITFL tears were randomized to a treatment group receiving injections of PRP or to a control group. All patients followed an identical rehabilitation protocol and RTP criteria. Patients were prospectively evaluated for clinical ability to return to full activity and residual pain. Dynamic ultrasound examinations were performed at initial examination and at 6 weeks post-injury to demonstrate re-stabilization of the syndesmosis joint and correlation with subjective outcome. All patients presented with a tear to the AITFL with dynamic syndesmosis instability in dorsiflexion-external rotation, and larger neutral tibia-fibula distance on ultrasound. Early diagnosis and treatment lead to shorter RTP, with 40.8 (±8.9) and 59.6 (±12.0) days for the PRP and control groups, respectively (p = 0.006). Significantly less residual pain upon return to activity was found in the PRP group; five patients (62.5 %) in the control group returned to play with minor discomfort versus one patient in the treatment group (12.5 %). One patient in the control group had continuous pain and disability and subsequently underwent syndesmosis reconstruction. Athletes suffering from high ankle sprains benefit from ultrasound-guided PRP injections with a shorter RTP, re-stabilization of the syndesmosis joint and less long-term residual pain. II.

Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).

PubMed

Dohan Ehrenfest, David M; Rasmusson, Lars; Albrektsson, Tomas

2009-03-01

The topical use of platelet concentrates is recent and its efficiency remains controversial. Several techniques for platelet concentrates are available; however, their applications have been confusing because each method leads to a different product with different biology and potential uses. Here, we present classification of the different platelet concentrates into four categories, depending on their leucocyte and fibrin content: pure platelet-rich plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; leucocyte- and platelet-rich plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan or GPS PRP; pure plaletet-rich fibrin (P-PRF), such as Fibrinet; and leucocyte- and platelet-rich fibrin (L-PRF), such as Choukroun's PRF. This classification should help to elucidate successes and failures that have occurred so far, as well as providing an objective approach for the further development of these techniques.

Growth factors and chronic wound healing: past, present, and future.

PubMed

Goldman, Robert

2004-01-01

Growth substances (cytokines and growth factors) are soluble signaling proteins affecting the process of normal wound healing. Cytokines govern the inflammatory phase that clears cellular and extracellular matrix debris. Wound repair is controlled by growth factors (platelet-derived growth factor [PDGF], keratinocyte growth factor, and transforming growth factor beta). Endogenous growth factors communicate across the dermal-epidermal interface. PDGF is important for most phases of wound healing. Becaplermin (PDGF-BB), the only growth factor approved by the Food and Drug Administration, requires daily application for neuropathic wound healing. Gene therapy is under development for more efficient growth factor delivery; a single application will induce constitutive growth factor expression for weeks. Based on dramatic preclinical animal studies, a phase 1 clinical trial planned on a PDGF genetic construct appears promising.

Fibroblast growth factor receptors in breast cancer.

PubMed

Wang, Shuwei; Ding, Zhongyang

2017-05-01

Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

PubMed

Lee, J S; Kim, J M; Hong, E K; Kim, S-O; Yoo, Y-J; Cha, J-H

2009-02-01

A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the inhibition of p38 delayed the process. These results indicate that heparin-binding epidermal growth factor-like growth factor may constitute a critical factor in the wound healing of human periodontal ligament cells by a mechanism that requires the activation of Erk1/2 via specific interaction with epidermal growth factor receptor 1.

Growth factors in the anterior segment: role in tissue maintenance, wound healing and ocular pathology.

PubMed

Klenkler, Bettina; Sheardown, Heather

2004-11-01

A number of growth factors and their associated receptors, including epidermal growth factor, transforming growth factor-beta, keratinocyte growth factor, hepatocyte growth factor, fibroblast growth factor and platelet-derived growth factor have been detected in the anterior segment of the eye. On binding to cellular receptors, these factors activate signalling cascades, which regulate functions including mitosis, differentiation, motility and apoptosis. Production of growth factors by corneal cells and their presence in the tear fluid and aqueous humour is essential for maintenance and renewal of normal tissue in the anterior eye and the prevention of undesirable immune or angiogenic reactions. Growth factors also play a vital role in corneal wound healing, mediating the proliferation of epithelial and stromal tissue and affecting the remodelling of the extracellular matrix (ECM). These functions depend on a complex interplay between growth factors of different types, the ECM, and regulatory mechanisms of the affected cells. Imbalances may lead to deficient wound healing and various ocular pathologies, including edema, neovascularization and glaucoma. Growth factors may be targeted in therapeutic ophthalmic applications, through exogenous application or selective inhibition, and may be used to elicit specific cellular responses to ophthalmic materials. A thorough understanding of the mechanism and function of growth factors and their actions in the complex environment of the anterior eye is required for these purposes. Growth factors, their function and mechanisms of action as well as the interplay between different growth factors based on recent in vitro and in vivo studies are presented.

Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications

PubMed Central

Ciarmela, Pasquapina; Islam, Md. Soriful; Reis, Fernando M.; Gray, Peter C.; Bloise, Enrrico; Petraglia, Felice; Vale, Wylie; Castellucci, Mario

2011-01-01

BACKGROUND Growth factors are proteins secreted by a number of cell types that are capable of modulating cellular growth, proliferation and cellular differentiation. It is well accepted that uterine cellular events such as proliferation and differentiation are regulated by sex steroids and their actions in target tissues are mediated by local production of growth factors acting through paracrine and/or autocrine mechanisms. Myometrial mass is ultimately modified in pregnancy as well as in tumour conditions such as leiomyoma and leiomyosarcoma. Leiomyomas, also known as fibroids, are benign tumours of the uterus, considered to be one of the most frequent causes of infertility in reproductive years in women. METHODS For this review, we searched the database MEDLINE and Google Scholar for articles with content related to growth factors acting on myometrium; the findings are hereby reviewed and discussed. RESULTS Different growth factors such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), heparin-binding EGF (HB-EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and TGF-β perform actions in myometrium and in leiomyomas. In addition to these growth factors, activin and myostatin have been recently identified in myometrium and leiomyoma. CONCLUSIONS Growth factors play an important role in the mechanisms involved in myometrial patho-physiology. PMID:21788281

Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

PubMed

Opgenorth, A; Nation, N; Graham, K; McFadden, G

1993-02-01

The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

Media composition: growth factors.

PubMed

Hegde, Aparna; Behr, Barry

2012-01-01

Despite the fact that the fundamental principle underlying the most common method of culture media constitution is that of mimicking the natural environment of the preimplantation embryo, one major difference that remains between current embryo culture media and in vivo conditions is the absence of growth factors in vitro. Numerous growth factors are known to be present in the in vivo environment of human and nonhuman preimplantation embryos, often with peak concentrations corresponding to when fertilization and preimplantation embryo growth would occur. Although these growth factors are found in very small concentrations, they have a profound effect on tissue growth and differentiation through attachment to factor-specific receptors on cell surfaces. Receptors for many different growth factors have also been detected in human preimplantation embryos. Preimplantation embryos themselves express many growth factors. The growth factors and receptors are metabolically costly to produce, and thus their presence in the environment of the preimplantation embryo and in the embryo respectively strongly implies that embryos are designed to encounter and respond to the corresponding factors. Studies of embryo coculture also indirectly suggest that growth factors can improve in vitro development. Several animal and human studies attest to a probable beneficial effect of addition of growth factors to culture media. However, there is still ambiguity regarding the exact role of growth factors in embryonic development, the optimal dose of growth factors to be added to culture media, the combinatorial effect and endocrine of growth factors in embryonic development.

Targeted delivery of growth factors in ischemic stroke animal models.

PubMed

Rhim, Taiyoun; Lee, Minhyung

2016-01-01

Ischemic stroke is caused by reduced blood supply and leads to loss of brain function. The reduced oxygen and nutrient supply stimulates various physiological responses, including induction of growth factors. Growth factors prevent neuronal cell death, promote neovascularization, and induce cell growth. However, the concentration of growth factors is not sufficient to recover brain function after the ischemic damage, suggesting that delivery of growth factors into the ischemic brain may be a useful treatment for ischemic stroke. In this review, various approaches for the delivery of growth factors to ischemic brain tissue are discussed, including local and targeting delivery systems. To develop growth factor therapy for ischemic stroke, important considerations should be taken into account. First, growth factors may have possible side effects. Thus, concentration of growth factors should be restricted to the ischemic tissues by local administration or targeted delivery. Second, the duration of growth factor therapy should be optimized. Growth factor proteins may be degraded too fast to have a high enough therapeutic effect. Therefore, delivery systems for controlled release or gene delivery may be useful. Third, the delivery systems to the brain should be optimized according to the delivery route.

Effect of growth factors on hyaluronan production by canine vocal fold fibroblasts.

PubMed

Hirano, Shigeru; Bless, Diane M; Heisey, Dennis; Ford, Charles N

2003-07-01

Hyaluronan (HYA) is considered to be a crucial factor in scarless wound healing and in maintaining tissue viscosity of the vocal fold lamina propria. In this study focusing on the effects of growth factors, we examined how HYA is produced and controlled in canine cultured vocal fold fibroblasts. Fibroblasts were taken from the lamina propria of the vocal folds of 8 dogs and cultured with and without growth factors. The production of HYA in the supernatant culture was quantitatively examined by enzyme-linked immunosorbent assay. Hepatocyte growth factor, epidermal growth factor, basic fibroblast growth factor, and transforming growth factor beta1 all stimulated HYA synthesis from vocal fold fibroblasts. These effects differed with the concentration of growth factors and the incubation period. We also examined how frequently the growth factors had to be administered in order to maintain appropriate levels of HYA. A single administration was sufficient to maintain appropriate HYA levels for at least 7 days. The present studies have demonstrated positive effects of growth factors in stimulating HYA production. Further in vivo study is needed to clarify the usefulness of these growth factors in the management of vocal fold scarring.

Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ayyagari, R.R.; Khan-Dawood, F.S.

Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2more » hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol /sup 125/I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function.« less

Growth factors, nutrient signaling, and cardiovascular aging.

PubMed

Fontana, Luigi; Vinciguerra, Manlio; Longo, Valter D

2012-04-13

Growth factors regulated by specific macronutrients have been shown to promote aging and accelerate mortality in the majority of the organisms studied. In particular, the enzymes activated by growth hormone, insulin, and insulin-like growth factor-1 in mammals and their orthologs in simple model organisms represent perhaps the best-understood proteins involved in the aging process. Dietary restriction, which reduces the level of insulin-like growth factor-1 and of other growth factors, has been associated with protection from diabetes, cancer, and cardiovascular diseases, and deficiencies in growth hormone signaling and insulin-like growth factor-1 are strongly associated with protection from cancer and diabetes in both mice and humans; however, their role in cardiac function and cardiovascular diseases is controversial. Here, we review the link between growth factors, cardiac function, and heart disease with focus on the cardioprotective and sensitizing effect of growth factors in both model organisms and humans.

Dirt or Diabetes

DTIC Science & Technology

2018-02-15

possible mutation in the fibroblast growth factor receptor 3 gene, and type 3, the most common, associated with insulin resistant states and...like growth factor receptor 1 (IGFR1), fibroblast growth factor receptors (FGFR), and epidermal growth factor receptor (EGFR), have all been proposed...as contributing factors. EGFR is a pivotal receptor because it interacts with several other growth factors (PDGF, TF-B, protein kinase C). They

Colostrum and Mature Human Milk of Women from London, Moscow, and Verona: Determinants of Immune Composition.

PubMed

Munblit, Daniel; Treneva, Marina; Peroni, Diego G; Colicino, Silvia; Chow, LiYan; Dissanayeke, Shobana; Abrol, Priya; Sheth, Shreya; Pampura, Alexander; Boner, Attilio L; Geddes, Donna T; Boyle, Robert J; Warner, John O

2016-11-03

Cytokines and growth factors in colostrum and mature milk may play an important role in infant immune maturation, and may vary significantly between populations. We aimed to examine associations between environmental and maternal factors, and human milk (HM) cytokine and growth factor levels. We recruited 398 pregnant/lactating women in the United Kingdom, Russia, and Italy. Participants underwent skin prick testing, questionnaire interview, and colostrum and mature milk sampling. HM cytokine and growth factor levels were quantified by electro-chemiluminescence. We found significant geographical variation in growth factor levels, but no evidence of variation between sites in cytokine detectability. There was an inverse correlation between time of milk sampling and growth factor levels in colostrum for Hepatocyte Growth Factor (HGF) and TGFβ1 and TGFβ3, but not TGFβ2, and levels were significantly higher in colostrum than mature milk for all growth factors. The kinetics of decline were different for each growth factor. Cytokines were present at much lower levels than growth factors, and the decline over time was less consistent. HM growth factors and cytokine levels vary between populations for unknown reasons. Levels of HM mediators decline at different rates postpartum, and these findings suggest specific biological roles for HM growth factors and cytokines in early postnatal development.

Colostrum and Mature Human Milk of Women from London, Moscow, and Verona: Determinants of Immune Composition

PubMed Central

Munblit, Daniel; Treneva, Marina; Peroni, Diego G.; Colicino, Silvia; Chow, LiYan; Dissanayeke, Shobana; Abrol, Priya; Sheth, Shreya; Pampura, Alexander; Boner, Attilio L.; Geddes, Donna T.; Boyle, Robert J.; Warner, John O.

2016-01-01

Cytokines and growth factors in colostrum and mature milk may play an important role in infant immune maturation, and may vary significantly between populations. We aimed to examine associations between environmental and maternal factors, and human milk (HM) cytokine and growth factor levels. We recruited 398 pregnant/lactating women in the United Kingdom, Russia, and Italy. Participants underwent skin prick testing, questionnaire interview, and colostrum and mature milk sampling. HM cytokine and growth factor levels were quantified by electro-chemiluminescence. We found significant geographical variation in growth factor levels, but no evidence of variation between sites in cytokine detectability. There was an inverse correlation between time of milk sampling and growth factor levels in colostrum for Hepatocyte Growth Factor (HGF) and TGFβ1 and TGFβ3, but not TGFβ2, and levels were significantly higher in colostrum than mature milk for all growth factors. The kinetics of decline were different for each growth factor. Cytokines were present at much lower levels than growth factors, and the decline over time was less consistent. HM growth factors and cytokine levels vary between populations for unknown reasons. Levels of HM mediators decline at different rates postpartum, and these findings suggest specific biological roles for HM growth factors and cytokines in early postnatal development. PMID:27827874

Temporal expression of growth factors triggered by epiregulin regulates inflammation development.

PubMed

Harada, Masaya; Kamimura, Daisuke; Arima, Yasunobu; Kohsaka, Hitoshi; Nakatsuji, Yuji; Nishida, Makoto; Atsumi, Toru; Meng, Jie; Bando, Hidenori; Singh, Rajeev; Sabharwal, Lavannya; Jiang, Jing-Jing; Kumai, Noriko; Miyasaka, Nobuyuki; Sakoda, Saburo; Yamauchi-Takihara, Keiko; Ogura, Hideki; Hirano, Toshio; Murakami, Masaaki

2015-02-01

In this study, we investigated the relationship between several growth factors and inflammation development. Serum concentrations of epiregulin, amphiregulin, betacellulin, TGF-α, fibroblast growth factor 2, placental growth factor (PLGF), and tenascin C were increased in rheumatoid arthritis patients. Furthermore, local blockades of these growth factors suppressed the development of cytokine-induced arthritis in mice by inhibiting chemokine and IL-6 expressions. We found that epiregulin expression was early and followed by the induction of other growth factors at different sites of the joints. The same growth factors then regulated the expression of epiregulin at later time points of the arthritis. These growth factors were increased in patients suffering from multiple sclerosis (MS) and also played a role in the development of an MS model, experimental autoimmune encephalomyelitis. The results suggest that the temporal expression of growth factors is involved in the inflammation development seen in several diseases, including rheumatoid arthritis and MS. Therefore, various growth factor pathways might be good therapeutic targets for various inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

PubMed

Lakshmanan, J; Landel, C P

1986-07-01

We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration.

PubMed

Dyondi, Deepti; Webster, Thomas J; Banerjee, Rinti

2013-01-01

Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF), and bone morphogenetic protein 7 (BMP7) were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.

Growth hormone deficiency - children

MedlinePlus

... be done include: Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 ( ... C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, ...

Epidermal growth factor- and hepatocyte growth factor-receptor activity in serum-free cultures of human hepatocytes.

PubMed

Runge, D M; Runge, D; Dorko, K; Pisarov, L A; Leckel, K; Kostrubsky, V E; Thomas, D; Strom, S C; Michalopoulos, G K

1999-02-01

Serum-free primary cultures of hepatocytes are a useful tool to study factors triggering hepatocyte proliferation and regeneration. We have developed a chemically defined serum-free system that allows human hepatocyte proliferation in the presence of epidermal growth factor and hepatocyte growth factor. DNA synthesis and accumulation were determined by [3H]thymidine incorporation and fluorometry, respectively. Western blot analyses and co-immunoprecipitations were used to investigate the association of proteins involved in epidermal growth factor and hepatocyte growth factor activation and signaling: epidermal growth factor receptor, hepatocyte growth factor receptor (MET), urokinase-type plasminogen activator and its receptor, and a member of the signal transducer and activator of transcription family, STAT-3. Primary human hepatocytes proliferated under serum-free conditions in a chemically defined medium for up to 12 days. Epidermal growth factor-receptor and MET were present and functional, decreasing over time. MET, urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor co-precipitated to varying degrees during the culture period. STAT-3 co-precipitated with epidermal growth factor-receptor and MET to varying degrees. Proliferation of human hepatocytes can improve by modification of a chemically defined medium originally used for rat hepatocyte cultures. In these long-term cultures of human hepatocytes, hepatocyte growth factor and epidermal growth factor can stimulate growth and differentiation by interacting with their receptors and initiating downstream signaling. This involves complex formation of the receptors with other plasma membrane components for MET (urokinase-type plasminogen activator in context of its receptor) and activation of STAT-3 for both receptors.

Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

DTIC Science & Technology

2009-10-01

AD_________________ Award Number: W81XWH-08-1-0708 TITLE: Fibroblast Growth Factor 2: an...September 2008 – 14 September 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fibroblast Growth Factor 2: an Epithelial Ductal Cell Growth Inhibitor...9 Fibroblast Growth Factor -2: an Epithelial Ductal Cell Growth Inhibitor that Drops Out in Breast Cancer

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer.

PubMed

Zammit, C; Coope, R; Gomm, J J; Shousha, S; Johnston, C L; Coombes, R C

2002-04-08

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.

Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

DTIC Science & Technology

2011-10-01

fibroblast   growth   factor   receptors  and  their  prognostic...AD_________________ Award Number: W81XWH-08-1-0708 TITLE: Fibroblast Growth Factor 2: an...September 2008 – 14 September 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fibroblast Growth Factor 2: an Epithelial Ductal Cell Growth

Delivery of growth factors for tissue regeneration and wound healing.

PubMed

Koria, Piyush

2012-06-01

Growth factors are soluble secreted proteins capable of affecting a variety of cellular processes important for tissue regeneration. Consequently, the self-healing capacity of patients can be augmented by artificially enhancing one or more processes important for healing through the application of growth factors. However, their application in clinics remains limited due to lack of robust delivery systems and biomaterial carriers. Interestingly, all clinically approved therapies involving growth factors utilize some sort of a biomaterial carrier for growth factor delivery. This suggests that biomaterial delivery systems are extremely important for successful usage of growth factors in regenerative medicine. This review outlines the role of growth factors in tissue regeneration, and their application in both pre-clinical animal models of regeneration and clinical trials is discussed. Additionally, current status of biomaterial substrates and sophisticated delivery systems such as nanoparticles for delivery of exogenous growth factors and peptides in humans are reviewed. Finally, issues and possible future research directions for growth factor therapy in regenerative medicine are discussed.

Liposomal gene transfer of keratinocyte growth factor improves wound healing by altering growth factor and collagen expression.

PubMed

Pereira, Clifford T; Herndon, David N; Rocker, Roland; Jeschke, Marc G

2007-05-15

Growth factors affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study, we thought to determine the interaction between keratinocyte growth factor (KGF) administered as liposomal cDNA with other dermal and epidermal growth factors and collagen synthesis in an acute wound. Rats received an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and Lac-Z gene (0.22 microg). Histological and immunohistochemical techniques were used to determine growth factor, collagen expression, and dermal and epidermal structure. KGF cDNA increased insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and fibroblast growth factor (FGF), decreased transforming growth factor-beta (TGF-beta), while it had no effect on platelet-derived growth factor (PDGF) levels in the wound. KGF cDNA significantly increased collagen Type IV at both the wound edge as well as the wound bed, while it had no effect on collagen Type I and III. KGF cDNA increased re-epithelialization, improved dermal regeneration, and increased neovascularization. Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III.

Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading

NASA Technical Reports Server (NTRS)

Decker, R. S.; Cook, M. G.; Behnke-Barclay, M.; Decker, M. L.

1995-01-01

Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

PubMed Central

Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

2013-01-01

Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer.

PubMed

Anan, K; Morisaki, T; Katano, M; Ikubo, A; Kitsuki, H; Uchiyama, A; Kuroki, S; Tanaka, M; Torisu, M

1996-03-01

Angiogenesis is a prerequisite for tumor growth and metastasis. Tumor angiogenesis may be mediated by several angiogenic factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-alpha, and basic fibroblast growth factor. Differential mRNA expressions of VEGF, PDGF (A chain), transforming growth factor-alpha and basic fibroblast growth factor in 32 primary invasive breast tumors were examined by reverse transcriptase-polymerase chain reaction. We analyzed relationships between mRNA expressions of these angiogenic factors and the degree of angiogenesis, tumor size, and metastasis. Quantification of angiogenesis was achieved by the immunohistochemical staining of endothelial cells with antibody to CD31. VEGF and PDGF-A mRNAs were expressed more frequently in breast tumors than in nontumor breast tissues, whereas no difference was found in expression frequency of either transforming growth factor-alpha or basic fibroblast growth factor mRNA. Vascular counts in tumors correlated with each expression frequency of VEGF and PDGF-A mRNA. PDGF-A mRNA was expressed more frequently in tumors with lymph node metastasis than in those without metastasis. Expression of VEGF and PDGF mRNAs detected by reverse transcriptase-polymerase chain reaction in breast tumors correlates with tumor-related characteristics of angiogenesis and metastatic potential. Analysis of these mRNAs by reverse transcriptase-polymerase chain reaction may be useful for assessing the biologic behavior of a breast tumor before surgical treatment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martino, Mikaël M.; Briquez, Priscilla S.; Maruyama, Kenta

Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of themore » ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.« less

Growth factor delivery: How surface interactions modulate release in vitro and in vivo

PubMed Central

King, William J.; Krebsbach, Paul H.

2013-01-01

Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

Fibroblast Growth Factors Stimulate Hair Growth through β-Catenin and Shh Expression in C57BL/6 Mice

PubMed Central

Lin, Wei-hong; Xiang, Li-Jun; Shi, Hong-Xue; Zhang, Jian; Jiang, Li-ping; Cai, Ping-tao; Lin, Zhen-Lang; Lin, Bei-Bei; Huang, Yan; Zhang, Hai-Lin; Fu, Xiao-Bing; Guo, Ding-Jiong; Li, Xiao-Kun; Wang, Xiao-Jie; Xiao, Jian

2015-01-01

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent. PMID:25685806

Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Galvez-Contreras, Alma Y.; Campos-Ordonez, Tania; Gonzalez-Castaneda, Rocio E.; Gonzalez-Perez, Oscar

2017-01-01

Growth factors (GFs) are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders. PMID:28751869

Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

NASA Astrophysics Data System (ADS)

Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

2016-09-01

Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

Nerve Growth Factor Expression Is Not Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma.

PubMed

Urabe, Kazuhide; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Hashimoto, Yasushi; Nakagawa, Naoya; Sasaki, Hayato; Hiyama, Eiso; Takahashi, Shinya; Sueda, Taijiro

2016-03-01

Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers. To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival. Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses. High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival. Intratumoral nerve growth factor expression is not associated with perineural invasion or recurrence-free and overall survival in patients with resected extrahepatic cholangiocarcinoma.

Changes in expression and secretion patterns of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway molecules during murine neural stem/progenitor cell differentiation in vitro☆

PubMed Central

Lu, Jiang; Lu, Kehuan; Li, Dongsheng

2012-01-01

In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells. PMID:25624789

Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

PubMed

Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

2017-05-01

Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

Clinical Application of Growth Factors and Cytokines in Wound Healing

PubMed Central

Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

2016-01-01

Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of non-healing wounds (e.g. pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted a nonline search of Medline and Pub Medical and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies and future research possibilities. In this review we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include: granulocyte-macrophage colony stimulating factor (GM-CSF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy. PMID:24942811

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.

PubMed

Cheung, Laurence C; Strickland, Deborah H; Howlett, Meegan; Ford, Jette; Charles, Adrian K; Lyons, Karen M; Brigstock, David R; Goldschmeding, Roel; Cole, Catherine H; Alexander, Warren S; Kees, Ursula R

2014-07-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. Copyright© Ferrata Storti Foundation.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

PubMed Central

Cheung, Laurence C.; Strickland, Deborah H.; Howlett, Meegan; Ford, Jette; Charles, Adrian K.; Lyons, Karen M.; Brigstock, David R.; Goldschmeding, Roel; Cole, Catherine H.; Alexander, Warren S.; Kees, Ursula R.

2014-01-01

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. PMID:24727816

The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy

PubMed Central

Tal, Reshef; Segars, James H.

2014-01-01

Background It is well established that tumors are dependent on angiogenesis for their growth and survival. Although uterine fibroids are known to be benign tumors with reduced vascularization, recent work demonstrates that the vasculature of fibroids is grossly and microscopically abnormal. Accumulating evidence suggests that angiogenic growth factor dysregulation may be implicated in these vascular and other features of fibroid pathophysiology. Methods Literature searches were performed in PubMed and Google Scholar for articles with content related to angiogenic growth factors and myometrium/leiomyoma. The findings are hereby reviewed and discussed. Results Multiple growth factors involved in angiogenesis are differentially expressed in leiomyoma compared with myometrium. These include epidermal growth factor (EGF), heparin-binding-EGF, vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-β and adrenomedullin. An important paradox is that although leiomyoma tissues are hypoxic, leiomyoma feature down-regulation of key molecular regulators of the hypoxia response. Furthermore, the hypoxic milieu of leiomyoma may contribute to fibroid development and growth. Notably, common treatments for fibroids such as GnRH agonists and uterine artery embolization (UAE) are shown to work at least partly via anti-angiogenic mechanisms. Conclusions Angiogenic growth factors play an important role in mechanisms of fibroid pathophysiology, including abnormal vasculature and fibroid growth and survival. Moreover, the fibroid's abnormal vasculature together with its aberrant hypoxic and angiogenic response may make it especially vulnerable to disruption of its vascular supply, a feature which could be exploited for treatment. Further experimental studies are required in order to gain a better understanding of the growth factors that are involved in normal and pathological myometrial angiogenesis, and to assess the potential of anti-angiogenic treatment strategies for uterine fibroids. PMID:24077979

Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs.

PubMed

Vilar, Jose M; Morales, Manuel; Santana, Angelo; Spinella, Giuseppe; Rubio, Mónica; Cuervo, Belen; Cugat, Ramón; Carrillo, Jose M

2013-07-02

Adipose-derived mesenchymal stem cell (ADMSC) therapy in regenerative medicine is a rapidly growing area of research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify the efficacy of different therapeutic strategies for the treatment of OA in dogs, but never with AD-MSC.The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA. Eight lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved after treatment of the OA groups, reaching 53.02% and 14.84% of body weight, respectively, at day 180, compared with only 43.56% and 12.16% at day 0. This study objectively demonstrated that intraarticular ADMSC therapy resulted in reduced lameness due to OA.

Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs

PubMed Central

2013-01-01

Background Adipose-derived mesenchymal stem cell (ADMSC) therapy in regenerative medicine is a rapidly growing area of research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify the efficacy of different therapeutic strategies for the treatment of OA in dogs, but never with AD-MSC. The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA. Results Eight lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved after treatment of the OA groups, reaching 53.02% and 14.84% of body weight, respectively, at day 180, compared with only 43.56% and 12.16% at day 0. Conclusion This study objectively demonstrated that intraarticular ADMSC therapy resulted in reduced lameness due to OA. PMID:23819757

Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans.

PubMed

Osman, Narin; Grande-Allen, K Jane; Ballinger, Mandy L; Getachew, Robel; Marasco, Silvana; O'Brien, Kevin D; Little, Peter J

2013-01-01

Calcific aortic valve disease is a progressive condition that shares some common pathogenic features with atherosclerosis. Transforming growth factor-β1 is a recognized mediator of atherosclerosis and is expressed in aortic valve lesions. Transforming growth factorβ1 stimulates glycosaminoglycan elongation of proteoglycans that is associated with increased lipid binding. We investigated the presence of transforming growth factor-β1 and downstream signaling intermediates in diseased human aortic valves and the effects of activated transforming growth factor-β1 receptor signaling on aortic valve interstitial cell proteoglycan synthesis and lipid binding as a possible mechanism for the initiation of the early lesion of calcific aortic valve disease. Diseased human aortic valve leaflets demonstrated strong immunohistochemical staining for transforming growth factor-β1 and phosphorylated Smad2/3. In primary porcine aortic valve interstitial cells, Western blots showed that transforming growth factor-β1 stimulated phosphorylation in both the carboxy and linker regions of Smad2/3, which was inhibited by the transforming growth factor-β1 receptor inhibitor SB431542. Gel electrophoresis and size exclusion chromatography demonstrated that SB431542 decreased transforming growth factor-β1-mediated [(35)S]-sulfate incorporation into proteoglycans in a dose-dependent manner. Further, in proteoglycans derived from transforming growth factor-β1-treated valve interstitial cells, gel mobility shift assays demonstrated that inhibition of transforming growth factor-β1 receptor signaling resulted in decreased lipid binding. Classic transforming growth factor-β1 signaling is present in human aortic valves in vivo and contributes to the modification of proteoglycans expressed by valve interstitial cells in vitro. These findings suggest that transforming growth factor-β1 may promote increased low-density lipoprotein binding in the early phases of calcific aortic valve disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantification of growth factor signaling and pathway cross talk by live-cell imaging.

PubMed

Gross, Sean M; Rotwein, Peter

2017-03-01

Peptide growth factors stimulate cellular responses through activation of their transmembrane receptors. Multiple intracellular signaling cascades are engaged following growth factor-receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluorescent live-cell imaging reporters that are readouts for two major growth factor-stimulated pathways, Ras-Raf-Mek-ERK and phosphatidylinositol (PI) 3-kinase-Akt. Incubation of cells with epidermal growth factor (EGF) resulted in rapid, robust, and sustained ERK signaling but shorter-term activation of Akt. In contrast, hepatocyte growth factor induced sustained Akt signaling but weak and short-lived ERK activity, and insulin-like growth factor-I stimulated strong long-term Akt responses but negligible ERK signaling. To address potential interactions between signaling pathways, we employed specific small-molecule inhibitors. In cells incubated with EGF or platelet-derived growth factor-AA, Raf activation and the subsequent stimulation of ERK reduced Akt signaling, whereas Mek inhibition, which blocked ERK activation, enhanced Akt and turned transient effects into sustained responses. Our results reveal that individual growth factors initiate signaling cascades that vary markedly in strength and duration and demonstrate in living cells the dramatic effects of cross talk from Raf and Mek to PI 3-kinase and Akt. Our data further indicate how specific growth factors can encode distinct cellular behaviors by promoting complex interactions among signaling pathways. Copyright © 2017 the American Physiological Society.

Release of growth factors and the effect of age, sex, and severity of injury after long bone fracture. A preliminary report.

PubMed

Pountos, Ippokratis; Georgouli, Theodora; Henshaw, Karen; Bird, Howard; Giannoudis, Peter V

2013-02-01

The systemic response after fracture is regulated by a complex mechanism involving numerous growth factors. In this study, we analyzed the kinetics of key growth factors following lower-limb long bone fracture. Human serum was isolated from 15 patients suffering from lower-limb long bone fracture (tibia/femur) requiring surgical fixation. The levels of platelet-derived growth factor (PDGF-BB), vascular edothelial growth factor (VEGF), insulin growth factor-I (IGF-I), and transforming growth factor β1 (TGF-β1) were assayed by colorimetric ELISA at different time points during the first week after fracture. 10 healthy volunteers made up the control group of the study. Serum levels of the growth factors measured were compared to age, sex, and injury severity score. We found that there was a decline in the levels of PDGF-BB, IGF-I and TGF-β1 during the first 3 days after fracture. However, VEGF levels remained unchanged. The levels of all the growth factors studied then increased, with the highest concentrations noted at day 7 after surgery. No correlation was found between circulating levels of growth factors and age, injury severity score (ISS), blood loss, or fluid administration. There are systemic mitogenic and osteogenic signals after fracture. Important growth factors are released into the peripheral circulation, but early after surgery it appears that serum levels of key growth factors fall. By 7 days postoperatively, the levels had increased considerably. Our findings should be considered in cases where autologous serum is used for ex vivo expansion of mesenchymal stem cells. There should be further evaluation of the use of these molecules as biomarkers of bone union.

The Influence of Platelet-Derived Growth Factor and Fibroblast Growth Factor 2 on Oligodendrocyte Development and Remyelination

DTIC Science & Technology

2004-01-01

OLIGODENDROCYTE DEVELOPMENT AND REMYELINATION 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...Z39-18 ABSTRACT Title: THE INFLUENCE OF PLATELET-DERIVED GROWTH FACTOR AND FIBROBLAST GROWTH FACTOR 2 ON OLIGODENDROCYTE DEVELOPMENT AND...GROWTH FACTOR 2 ON OLIGODENDROCYTE DEVELOPMENT AND REMYELINATION by Joshua C. Murtie Thesis/dissertation submitted to the

Effect of combined locally delivered growth factors and systemic sildenafil citrate on microrecanalization in biodegradable conduit for vas deferens reconstruction.

PubMed

Rosevear, Henry M; Krishnamachari, Yogita; Ariza, Carlos A; Mallapragada, Surya K; Salem, Aliasger K; Griffith, Thomas S; De Young, Barry R; Wald, Moshe

2012-04-01

To investigate the effect of the combination of locally delivered growth factors and oral sildenafil citrate on cross-conduit microrecanalization. A total of 42 rats were divided into 7 groups. Of the 42 rats, 6 underwent bilateral vasectomy and bilateral end-to-end vasovasostomy and 12 underwent bilateral vasectomy. Of the latter 12, 6 received sildenafil citrate orally (10 mg/kg/d) for 24 weeks and 6 received placebo. A total of 24 rats underwent bilateral vasectomy and bilateral reconstruction with implantation of a 5-mm biodegradable conduit that bridged the 2 vasal ends. Of the 24 rats with conduits, 12 also had 250 pg of transforming growth factor-β and 12.5 pg of platelet-derived growth factor-β sustained release nanoparticles placed in immediate proximity to the conduit. The remaining 12 rats with conduits (6 without growth factors and 6 with growth factors) also received sildenafil citrate orally (10 mg/kg/d) for 24 weeks; the others received placebo. The reconstructed segments were harvested for histologic examination at 24 weeks. Five of 6 primary vasovasostomy and no vasectomy-only rats sired litters. Significantly more microcanals per conduit were observed in rats receiving sildenafil citrate: without growth factors, 3.9 vs. 0 canals/conduit (P < 0.001); with growth factors, 5.5 vs. 0.25 canals/conduit (P < 0.001). The rats receiving sildenafil citrate with growth factors showed a trend toward more microcanals per conduit than the rats receiving sildenafil citrate without growth factors (5.5 vs 3.9; P = .10). Rats receiving growth factors but no sildenafil citrate did not produce more canals than the rats receiving neither growth factor nor sildenafil citrate (0.25 vs 0; P = NS). Orally administered sildenafil citrate enhances formation of microcanalization after postvasectomy reconstruction using a biodegradable conduit in a rat model. Locally delivered growth factors appear to increase the number of microcanals. Copyright © 2012 Elsevier Inc. All rights reserved.

Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

PubMed Central

Johns, D.E.; Athanasiou, K.A.

2010-01-01

Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

PubMed

Tanigawa, T; Ahluwalia, A; Watanabe, T; Arakawa, T; Tarnawski, A S

2015-08-01

A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100β protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing locally administered exogenous nerve growth factor is retained in gastric tissue and is taken up by endothelial, neural, muscle and epithelial cells. This is likely the basis for the therapeutic action of locally administered nerve growth factor and its stimulation of angiogenesis, tissue regeneration and gastric ulcer healing.

Conditioned media from a renal cell carcinoma cell line demonstrates the presence of basic fibroblast growth factor.

PubMed

Mydlo, J H; Zajac, J; Macchia, R J

1993-09-01

In a previous report, we demonstrated the isolation and purification of a heparin binding growth factor from human renal carcinoma, and suggested that this growth factor may play a role in the neovascularity and growth of the tumor. In this report, we demonstrate that the growth of the renal cell carcinoma cell line RC29 is stimulated by the addition of exogenous fibroblast growth factor (FGF), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha). Also, media conditioned by this cell line was able to stimulate growth of the A431 vulvar tumor cell line, known for its high concentration of EGF receptors, 3T3 fibroblasts, human umbilical vein (HUV) cells and RC29 cells. Using heparin-sepharose chromatography and then SDS polyacrylamide gel electrophoresis (PAGE), we were able to demonstrate several proteins in the conditioned media of the RC29 cell line. Using Western blot analysis, we detected that at least one of the proteins expressed in this conditioned media was FGF and that it belongs to the basic, not acidic, family of fibroblast growth factors. These findings suggest that renal tumors may express growth factors that may play a direct role in maintaining their unrestricted proliferation.

Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth Factor Expression from Keratinocytes and Endothelial Cells*

PubMed Central

Adase, Christopher A.; Borkowski, Andrew W.; Zhang, Ling-juan; Williams, Michael R.; Sato, Emi; Sanford, James A.

2016-01-01

A critical function for skin is that when damaged it must simultaneously identify the nature of the injury, repair barrier function, and limit the intrusion of pathogenic organisms. These needs are carried out through the detection of damage-associated molecular patterns (DAMPs) and a response that includes secretion of cytokines, chemokines, growth factors, and antimicrobial peptides (AMPs). In this study, we analyzed how non-coding double-stranded RNA (dsRNAs) act as a DAMP in the skin and how the human cathelicidin AMP LL-37 might influence growth factor production in response to this DAMP. dsRNA alone significantly increased the expression of multiple growth factors in keratinocytes, endothelial cells, and fibroblasts. Furthermore, RNA sequencing transcriptome analysis found that multiple growth factors increase when cells are exposed to both LL-37 and dsRNA, a condition that mimics normal wounding. Quantitative PCR and/or ELISA validated that growth factors expressed by keratinocytes in these conditions included, but were not limited to, basic fibroblast growth factor (FGF2), heparin-binding EGF-like growth factor (HBEGF), vascular endothelial growth factor C (VEGFC), betacellulin (BTC), EGF, epiregulin (EREG), and other members of the transforming growth factor β superfamily. These results identify a novel role for DAMPs and AMPs in the stimulation of repair and highlight the complex interactions involved in the wound environment. PMID:27048655

Quantification of growth factor signaling and pathway cross talk by live-cell imaging

PubMed Central

Gross, Sean M.

2017-01-01

Peptide growth factors stimulate cellular responses through activation of their transmembrane receptors. Multiple intracellular signaling cascades are engaged following growth factor–receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluorescent live-cell imaging reporters that are readouts for two major growth factor-stimulated pathways, Ras–Raf–Mek–ERK and phosphatidylinositol (PI) 3-kinase–Akt. Incubation of cells with epidermal growth factor (EGF) resulted in rapid, robust, and sustained ERK signaling but shorter-term activation of Akt. In contrast, hepatocyte growth factor induced sustained Akt signaling but weak and short-lived ERK activity, and insulin-like growth factor-I stimulated strong long-term Akt responses but negligible ERK signaling. To address potential interactions between signaling pathways, we employed specific small-molecule inhibitors. In cells incubated with EGF or platelet-derived growth factor-AA, Raf activation and the subsequent stimulation of ERK reduced Akt signaling, whereas Mek inhibition, which blocked ERK activation, enhanced Akt and turned transient effects into sustained responses. Our results reveal that individual growth factors initiate signaling cascades that vary markedly in strength and duration and demonstrate in living cells the dramatic effects of cross talk from Raf and Mek to PI 3-kinase and Akt. Our data further indicate how specific growth factors can encode distinct cellular behaviors by promoting complex interactions among signaling pathways. PMID:28100485

Endosomal receptor kinetics determine the stability of intracellular growth factor signalling complexes

PubMed Central

Tzafriri, A. Rami; Edelman, Elazer R.

2006-01-01

There is an emerging paradigm that growth factor signalling continues in the endosome and that cell response to a growth factor is defined by the integration of cell surface and endosomal events. As activated receptors in the endosome are exposed to a different set of binding partners, they probably elicit differential signals compared with when they are at the cell surface. As such, complete appreciation of growth factor signalling requires understanding of growth factor–receptor binding and trafficking kinetics both at the cell surface and in endosomes. Growth factor binding to surface receptors is well characterized, and endosomal binding is assumed to follow surface kinetics if one accounts for changes in pH. Yet, specific binding kinetics within the endosome has not been examined in detail. To parse the factors governing the binding state of endosomal receptors we analysed a whole-cell mathematical model of epidermal growth factor receptor trafficking and binding. We discovered that the stability of growth factor–receptor complexes within endosomes is governed by three primary independent factors: the endosomal dissociation constant, total endosomal volume and the number of endosomal receptors. These factors were combined into a single dimensionless parameter that determines the endosomal binding state of the growth factor–receptor complex and can distinguish different growth factors from each other and different cell states. Our findings indicate that growth factor binding within endosomal compartments cannot be appreciated solely on the basis of the pH-dependence of the dissociation constant and that the concentration of receptors in the endosomal compartment must also be considered. PMID:17117924

Hair growth-promoting effect of Geranium sibiricum extract in human dermal papilla cells and C57BL/6 mice.

PubMed

Boisvert, William A; Yu, Miri; Choi, Youngbin; Jeong, Gi Hee; Zhang, Yi-Lin; Cho, Sunghun; Choi, Changsun; Lee, Sanghyun; Lee, Bog-Hieu

2017-02-13

Geranium sibiricum L. has been used as a medicinal plant to treat diarrhea, bacterial infection, and cancer in Bulgaria, Peru, and Korea. However, its hair growth-promoting effect was not investigated so far. This study examined the effects of Geranium sibiricum L. extract (GSE) on hair growth, using in vitro and in vivo models. Antioxidant, proliferation and migration assay of GSE was performed with human dermal papilla cells (hDPCs). Hair-growth promoting effect was measured in animal model. Relative expression of interleukin-1, vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor beta 1 was determined by real time RT-PCR. Expression of Ki-67 and stem cell factor were analyzed by immunohistochemistry. GSE treatment proliferated and migrated human dermal papilla cells (hDPCs) more than treatment of 10 μM minoxidil. GSE significantly stimulated the expression of Ki-67 protein and the mRNA levels of hepatocyte growth factor and vascular endothelial growth factor in hDPCs. Topical application of 1,000 ppm GSE for 3 weeks promoted more significant hair growth on shaved C57BL/6 mice than did 5% minoxidil. The histological morphology of hair follicles demonstrated an active anagen phase with the induction of stem cell factor. GSE treatment significantly reduced the number of mast cells and the expression of transforming growth factor beta 1 in mouse skin tissues. These results demonstrated that GSE promotes hair growth in vitro and in vivo by regulating growth factors and the cellular response.

Hair-growth-promoting effect of conditioned medium of high integrin α6 and low CD 71 (α6bri/CD71dim) positive keratinocyte cells.

PubMed

Won, Chong Hyun; Jeong, Yun-Mi; Kang, Sangjin; Koo, Tae-Sung; Park, So-Hyun; Park, Ki-Young; Sung, Young-Kwan; Sung, Jong-Hyuk

2015-02-19

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells.

Recombinant Human Acidic Fibroblast Growth Factor (aFGF) Expressed in Nicotiana benthamiana Potentially Inhibits Skin Photoaging.

PubMed

Ha, Jang-Ho; Kim, Ha-Neul; Moon, Ki-Beom; Jeon, Jae-Heung; Jung, Dai-Hyun; Kim, Su-Jung; Mason, Hugh S; Shin, Seo-Yeon; Kim, Hyun-Soon; Park, Kyung-Mok

2017-07-01

Responding to the need for recombinant acidic fibroblast growth factor in the pharmaceutical and cosmetic industries, we established a scalable expression system for recombinant human aFGF using transient and a DNA replicon vector expression in Nicotiana benthamiana . Recombinant human-acidic fibroblast growth factor was recovered following Agrobacterium infiltration of N. benthamiana . The optimal time point at which to harvest recombinant human acidic fibroblast growth factor expressing leaves was found to be 4 days post-infiltration, before necrosis was evident. Commassie-stained SDS-PAGE gels of His-tag column eluates, concentrated using a 10 000 molecular weight cut-off column, showed an intense band at the expected molecular weight for recombinant human acidic fibroblast growth factor. An immunoblot confirmed that this band was recombinant human acidic fibroblast growth factor. Up to 10 µg recombinant human-acidic fibroblast growth factor/g of fresh leaves were achieved by a simple affinity purification protocol using protein extract from the leaves of agroinfiltrated N. benthamiana . The purified recombinant human acidic fibroblast growth factor improved the survival rate of UVB-irradiated HaCaT and CCD-986sk cells approximately 89 and 81 %, respectively. N. benthamiana -derived recombinant human acidic fibroblast growth factor showed similar effects on skin cell proliferation and UVB protection compared to those of Escherichia coli -derived recombinant human acidic fibroblast growth factor. Additionally, N. benthamiana- derived recombinant human acidic fibroblast growth factor increased type 1 procollagen synthesis up to 30 % as well as reduced UVB-induced intracellular reactive oxygen species generation in fibroblast (CCD-986sk) cells.UVB is a well-known factor that causes various types of skin damage and premature aging. Therefore, the present study demonstrated that N. benthamiana -derived recombinant human acidic fibroblast growth factor effectively protects skin cell from UVB, suggesting its potential use as a cosmetic or therapeutic agent against skin photoaging. Georg Thieme Verlag KG Stuttgart · New York.

Skin problems and EGFR-tyrosine kinase inhibitor

PubMed Central

Kozuki, Toshiyuki

2016-01-01

Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities. PMID:26826719

A gravimetric analysis of protein-oligosaccharide interactions.

PubMed

Rudd, T; Gallagher, J T; Ron, D; Nichols, R J; Fernig, D G

2003-04-01

Interactions between an immobilized, heparin-derived octasaccharide and growth factors have been observed using a quartz crystal microbalance-dissipation (QCM-D). This device can measure the amount of growth factors binding to the octasaccharide surface and also the change of dissipation of the surface. Dissipation is a measure of how the adhered material 'damps' the surface vibrations. The octasaccharides were anchored through their reducing ends by the intermediary of the alkanethiol molecule, which covalently binds to the crystal surface through the thiol group. As expected, heparin sulphate binding growth factors bound to the octasaccharide, but the change in mass of growth factor bound per unit change in dissipation is different for the different growth factors. Suggesting that the structures of the various growth factor-octasaccharide complexes are different, therefore, indicates that the change in dissipation can give insights into the structure, orientation and packing of the oligosaccharide-growth factor complexes.

The effect of growth factors on both collagen synthesis and tensile strength of engineered human ligaments.

PubMed

Hagerty, Paul; Lee, Ann; Calve, Sarah; Lee, Cassandra A; Vidal, Martin; Baar, Keith

2012-09-01

Growth factors play a central role in the development and remodelling of musculoskeletal tissues. To determine which growth factors optimized in vitro ligament formation and mechanics, a Box-Behnken designed array of varying concentrations of growth factors and ascorbic acid were applied to engineered ligaments and the collagen content and mechanics of the grafts were determined. Increasing the amount of transforming growth factor (TGF) β1 and insulin-like growth factor (IGF)-1 led to an additive effect on ligament collagen and maximal tensile load (MTL). In contrast, epidermal growth factor (EGF) had a negative effect on both collagen content and MTL. The predicted optimal growth media (50 μg/ml TGFβ, IGF-1, and GDF-7 and 200 μM ascorbic acid) was then validated in two separate trials: showing a 5.7-fold greater MTL and 5.2-fold more collagen than a minimal media. Notably, the effect of the maximized growth media was scalable such that larger constructs developed the same material properties, but larger MTL. These results show that optimizing the interactions between growth factors and engineered ligament volume results in an engineered ligament of clinically relevant function. Copyright © 2012 Elsevier Ltd. All rights reserved.

Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas.

PubMed

Chen, Xiaochuan; Rozance, Paul J; Hay, William W; Limesand, Sean W

2012-05-01

Placental insufficiency results in intrauterine growth restriction (IUGR), impaired fetal insulin secretion and less fetal pancreatic β-cell mass, partly due to lower β-cell proliferation rates. Insulin-like growth factors (IGFs) and fibroblast growth factors (FGFs) regulate fetal β-cell proliferation and pancreas development, along with transcription factors, such as pancreatic and duodenal homeobox 1 (PDX-1). We determined expression levels for these growth factors, their receptors and IGF binding proteins in ovine fetal pancreas and isolated islets. In the IUGR pancreas, relative mRNA expression levels of IGF-I, PDX-1, FGF7 and FGFR2IIIb were 64% (P < 0.01), 76% (P < 0.05), 76% (P < 0.05) and 52% (P < 0.01) lower, respectively, compared with control fetuses. Conversely, insulin-like growth factor binding protein 2 (IGFBP-2) mRNA and protein concentrations were 2.25- and 1.2-fold greater (P < 0.05) in the IUGR pancreas compared with controls. In isolated islets from IUGR fetuses, IGF-II and IGFBP-2 mRNA concentrations were 1.5- and 3.7-fold greater (P < 0.05), and insulin mRNA was 56% less (P < 0.05) than control islets. The growth factor expression profiles for IGF and FGF signaling pathways indicate that declines in β-cell mass are due to decreased growth factor signals for both pancreatic progenitor epithelial cell and mature β-cell replication.

TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

EPA Science Inventory

TITLE:
TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

PubMed

Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

2018-04-11

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

PubMed

Chen, Guobao; Lv, Yonggang

2015-01-01

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

Effects of Non-Collagenous Proteins, TGF-β1, and PDGF-BB on Viability and Proliferation of Dental Pulp Stem Cells

PubMed Central

Tabatabaei, Fahimeh Sadat

2016-01-01

ABSTRACT Objectives The dentin matrix servers as a reservoir of growth factors, sequestered during dentinogenesis. The aim of this study was to assess the viability and proliferation of dental pulp stem cells in the presence of dentin matrix-derived non-collagenous proteins and two growth factors; platelet-derived growth factor BB and transforming growth factor beta 1. Material and Methods The dental pulp cells were isolated and cultured. The dentin proteins were extracted and purified. The MTT assay was performed for assessment of cell viability and proliferation in the presence of different concentrations of dentin proteins and growth factors during 24 - 72 h post-treatment. Results The cells treated with 250 ng/mL dentin proteins had the best viability and proliferation ability in comparison with other concentrations (P < 0.05). The MTT assay demonstrated that cells cultured with 5 ng/mL platelet-derived growth factor BB had the highest viability at each time point as compared to other groups (P < 0.05). However, in presence of platelet-derived growth factor BB alone and in combination with transforming growth factor beta 1 and dentin proteins (10 ng/mL), significant higher viability was seen at all time points (P < 0.05). The least viability and proliferation at each growth factor concentration was seen in cells treated with combination of transforming growth factor beta 1 and dentin proteins at 72 h (P < 0.05). Conclusions The results indicated that the triple combination of growth factors and matrix-derived non-collagenous proteins (especially at 10 ng/mL concentration) has mitogenic effect on dental pulp stem cells. PMID:27099698

Potential role of fibroblast growth factor in enhancement of fracture healing.

PubMed

Radomsky, M L; Thompson, A Y; Spiro, R C; Poser, J W

1998-10-01

Fibroblast growth factors are present in significant amounts in bone and several studies have suggested that they may be involved in normal fracture healing. It is well established that fibroblast growth factors have mitogenic and angiogenic activity on mesoderm and neuroectoderm derived cells. Of particular interest as a member of the fibroblast growth factor family, basic fibroblast growth factor stimulates mitogenesis, chemotaxis, differentiation, and angiogenesis. It also plays an important role in the development of vascular, nervous, and skeletal systems, promotes the maintenance and survival of certain tissues, and stimulates wound healing and tissue repair. Animal studies have shown that the direct injection of fibroblast growth factor into fresh fractures stimulates callus formation, which provides mechanical stability to the fracture, accelerates healing, and restores competence. The matrix used to present the fibroblast growth factor at the fracture site plays a critical role in the effectiveness of the treatment. The evaluation of injectable basic fibroblast growth factor in a sodium hyaluronate gel for its effectiveness in stimulating fracture healing is described. When applied directly into a freshly created fracture in the rabbit fibula, a single injection of the basic fibroblast growth factor and hyaluronan results in the stimulation of callus formation, increased bone formation, and earlier restoration of mechanical strength at the fracture site. The hyaluronan gel serves as a reservoir that sequesters the basic fibroblast growth factor at the injection site for the length of time necessary to create an environment conducive to fracture healing. It is concluded that basic fibroblast growth factor and sodium hyaluronate act synergistically to accelerate fracture healing and that the combination is suitable for clinical evaluation as a therapy in fracture treatment.

In vitro comparison of the efficacy of TGF-β1 and PDGF-BB in combination with freeze-dried bone allografts for induction of osteogenic differentiation in MG-63 osteoblast-like cells.

PubMed

Vahabi, Surena; Torshabi, Maryam; Esmaeil Nejad, Azadeh

2016-12-01

Predictable regeneration of alveolar bone defects has always been a challenge in implant dentistry. Bone allografts are widely used bone substitutes with controversial osteoinductive activity. This in vitro study aimed to assess the osteogenic potential of some commercially available freeze-dried bone allografts supplemented with human recombinant platelet-derived growth factor-BB and transforming growth factor beta-1. Cell viability, mineralization, and osteogenic gene expression of MG-63 osteoblast-like cells were compared among the allograft alone, allograft/platelet-derived growth factor-BB, allograft/transforming growth factor beta-1, and allograft/platelet-derived growth factor-BB/transforming growth factor beta-1 groups. The methyl thiazol tetrazolium assay, real-time quantitative reverse transcription polymerase chain reaction and alizarin red staining were performed, respectively, for assessment of cell viability, differentiation, and mineralization at 24-72 h post treatment. The allograft with greater cytotoxic effect on MG-63 cells caused the lowest differentiation among the groups. In comparison with allograft alone, allograft/transforming growth factor beta-1, and allograft/transforming growth factor beta-1/platelet-derived growth factor-BB caused significant upregulation of bone sialoprotein and osteocalcin osteogenic mid-late marker genes, and resulted in significantly higher amounts of calcified nodules especially in mineralized non-cytotoxic allograft group. Supplementation of platelet-derived growth factor-BB alone in 5 ng/mL concentration had no significant effect on differentiation or mineralization markers. According to the results, transforming growth factor beta-1 acts synergistically with bone allografts to enhance the osteogenic differentiation potential. Therefore, this combination may be useful for rapid transformation of undifferentiated cells into bone-forming cells for bone regeneration. However, platelet-derived growth factor-BB supplementation did not support this synergistic ability to enhance osteogenic differentiation and thus, further investigations are required.

A review of the influence of growth factors and cytokines in in vitro human keratinocyte migration.

PubMed

Peplow, Philip V; Chatterjee, Marissa P

2013-04-01

Keratinocyte migration from the wound edge is a crucial step in the reepithelization of cutaneous wounds. Growth factors and cytokines, released from cells that invade the wound matrix, play an important role, and several in vitro assays have been performed to elucidate this. The purposes of this study were to review in vitro human studies on keratinocyte migration to identify those growth factors or cytokines that stimulate keratinocyte migration and whether these assays might serve as a screening procedure prior to testing combinations of growth factors or cytokines to promote wound closure in vivo. Research papers investigating effect of growth factors and cytokines on human keratinocyte migration in vitro were retrieved from library sources, PubMed databases, reference lists of papers, and searches of relevant journals. Fourteen different growth factors and cytokines enhanced migration in scratch wound assay and HGF together with TGF-β, and IGF-1 with EGF, were more stimulatory than either growth factor alone. HGF with TGF-β1 had a greater chemokinetic effect than either growth factor alone in transmigration assay. TGF-β1, FGF-7, FGF-2 and AGF were chemotactic to keratinocytes. EGF, TGF-α, IL-1α, IGF and MGSA enhanced cell migration on ECM proteins. Many growth factors and cytokines enhanced migration of keratinocytes in vitro, and certain combinations of growth factors were more stimulatory than either alone. These and other combinations that stimulate keratinocyte migration in vitro should be tested for effect on wound closure and repair in vivo. The scratch wound assay provides a useful, inexpensive and easy-to-perform screening method for testing individual or combinations of growth factors or cytokines, or growth factors combined with other modalities such as laser irradiation, prior to performing wound healing studies with laboratory animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

PubMed

Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

2006-08-01

Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer cell lines. Gefitinib, erlotinib and NVP-AEE788 caused a significant growth inhibition in vitro; however, there was a significant difference in efficacy (NVP-AEE788>erlotinib>gefitinib). After 14 days of in-vivo treatment, using the chimeric mouse model, tumors had a significantly reduced volume and mass after NVP-AEE788, but not after erlotinib treatment, as compared with placebo. Reduction of proliferation (signalling via the mitogen-activated protein kinase pathway), induction of apoptosis and inhibition of angiogenesis were the main mechanisms of drug action. No significant reduction of anti-apoptotic AKT phosphorylation, however, occurred, which may be a possible counter mechanism of the tumor. Epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 expression was detectable in biliary tract cancer, and receptor inhibition exerts marked effects on tumor growth in vitro and in vivo, which was strongest for the dual EGFR/ErbB-2 inhibitor NVP-AEE788. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.

On the dimensionality of the stress-related growth scale: one, three, or seven factors?

PubMed

Roesch, Scott C; Rowley, Anthony A; Vaughn, Allison A

2004-06-01

We examined the factorial validity and dimensionality of the Stress-Related Growth Scale (SRGS; Park, Cohen, & Murch, 1996) using a large multiethnic sample (n = 1,070). Exploratory and confirmatory factor analyses suggested that a multidimensional representation of the SRGS fit better than a unidimensional representation. Specifically, we cross-validated both a 3-factor model and a 7-factor model using confirmatory factor analysis and were shown to be invariant across gender and ethnic groups. The 3-factor model was represented by global dimensions of growth that included rational/mature thinking, affective/emotional growth, and religious/spiritual growth. We replicated the 7-factor model of Armeli, Gunthert, and Cohen (2001) and it represented more specific components of growth such as Self-Understanding and Treatment of Others. However, some factors of the 7-factor model had questionable internal consistency and were strongly intercorrelated, suggesting redundancy. The findings support the notion that the factor structure of both the original 1-factor and revised 7-factor models are unstable and that the 3-factor model developed in this research has more reliable psychometric properties and structure.

Endocrinological control of growth.

PubMed

Sizonenko, P C

1978-01-01

Many endocrinological factors control cellular growth of different tissues (cell multiplication and cell volume) and skeletal growth. The role of neuro-transmitters and of hypothalamic releasing and inhibiting factors of growth hormone secretion will be reviewed. The importance of the somatomedins on cartilage growth will be stressed. Thyroid hormones, androgens, and oestrogens have important stimulating actions on skeletal growth and maturation. Conversely, glucocorticoids have an important inhibitory effect on growth. The precise roles of these hormone factors in the regulation of growth hormone secretion, somatomedin production and tissue growth, particularly the cartilage, remain to be completely elucidated.

Separation of cell survival, growth, migration, and mesenchymal transdifferentiation effects of fibroblast secretome on tumor cells of head and neck squamous cell carcinoma.

PubMed

Metzler, Veronika Maria; Pritz, Christian; Riml, Anna; Romani, Angela; Tuertscher, Raphaela; Steinbichler, Teresa; Dejaco, Daniel; Riechelmann, Herbert; Dudás, József

2017-11-01

Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast-secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial-mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1.Tumor cell self-produced factors were sufficient to ensure tumor cell survival and basic cell growth, but fibroblast-secreted paracrine factors significantly increased cell proliferation, migration, and epithelial-mesenchymal transition-related phenotype changes in tumor cells. Transforming growth factor beta-1 generated individually migrating disseminating tumor cell groups or single cells separated from the tumor cell nest, which were characterized by reduced E-cadherin expression. At the same time, transforming growth factor beta-1 inhibited tumor cell proliferation under serum-starved conditions. Neutralizing transforming growth factor beta antibody reduced the cell migration support of fibroblast-conditioned medium. Transforming growth factor beta-1 as a single factor was sufficient for generation of disseminating tumor cells from epithelial tumor cell nests, while other fibroblast paracrine factors supported tumor nest outgrowth. Different fibroblast-released factors might support tumor cell proliferation and invasion, as two separate effects.

Hair-Growth-Promoting Effect of Conditioned Medium of High Integrin α6 and Low CD 71 (α6bri/CD71dim) Positive Keratinocyte Cells

PubMed Central

Won, Chong Hyun; Jeong, Yun-Mi; Kang, Sangjin; Koo, Tae-Sung; Park, So-Hyun; Park, Ki-Young; Sung, Young-Kwan; Sung, Jong-Hyuk

2015-01-01

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells. PMID:25706512

Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.

2008-11-14

REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration

PubMed Central

2014-01-01

Background Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Methods Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Results Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. Conclusions Taken together, these results demonstrate that dHACM grafts: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds. PMID:24817999

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration.

PubMed

Koob, Thomas J; Lim, Jeremy J; Massee, Michelle; Zabek, Nicole; Rennert, Robert; Gurtner, Geoffrey; Li, William W

2014-01-01

Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. TAKEN TOGETHER, THESE RESULTS DEMONSTRATE THAT DHACM GRAFTS: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds.

Evaluation of the Effects of Platelet-Rich Plasma (PRP) Therapy Involved in the Healing of Sports-Related Soft Tissue Injuries

PubMed Central

Middleton, Kellie K.; Barro, Victor; Muller, Bart; Terada, Satosha; Fu, Freddie H.

2012-01-01

Abstract Musculoskeletal injuries are the most common cause of severe long-term pain and physical disability, and affect hundreds of millions of people around the world. One of the most popular methods used to biologically enhance healing in the fields of orthopaedic surgery and sports medicine includes the use of autologous blood products, namely, platelet rich plasma (PRP). PRP is an autologous concentration of human platelets to supra-physiologic levels. At baseline levels, platelets function as a natural reservoir for growth factors including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and insulin-like growth factor (IGF-I). PRP is commonly used in orthopaedic practice to augment healing in sports-related injuries of skeletal muscle, tendons, and ligaments. Despite its pervasive use, the clinical efficacy of PrP therapy and varying mechanisms of action have yet to be established. Basic science research has revealed that PRP exerts is effects through many downstream events secondary to release of growth factors and other bioactive factors from its alpha granules. These effects may vary depending on the location of injury and the concentration of important growth factors involved in various soft tissue healing responses. This review focuses on the effects of PrP and its associated bioactive factors as elucidated in basic science research. Current findings in PRP basic science research, which have shed light on its proposed mechanisms of action, have opened doors for future areas of PrP research. PMID:23576936

FGFR4 Downregulation of Cell Adhesion in Prostate Cancer

DTIC Science & Technology

2008-09-01

Fibroblast Growth Factor Receptor 4, is a member of the FGFR family of RTK ( receptor tyrosine kinase) growth factor receptors . A common...work supported by this award: Cancer Research Coordinating Committee (CRCC) Intersection of NF- B and Fibroblast Growth Factor Receptor Signaling...disease. REFERENCES 1. Wang J, Stockton DW, Ittmann M. The fibroblast growth factor receptor -4

Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis

DTIC Science & Technology

2009-10-01

AD_________________ Award Number: W81XWH-06-1-0763 TITLE: Role of Fibroblast Growth Factor ...2009 4. TITLE AND SUBTITLE Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development 5a. CONTRACT NUMBER and Tumorigenesis...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS Fibroblast Growth Factor Binding Protein-1

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

PubMed

Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

2017-05-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

Growth factors in urologic tissues: detection, characterization, and clinical applications.

PubMed

Mydlo, J H; Macchia, R J

1992-12-01

During the last two decades, enormous strides have been made in understanding cellular and molecular biology. The direction of treatment of many neoplasms and other diseases are starting at the microscopic level. Growth factors are polypeptides that play a part in the development and maintenance of living tissues. We, as well as others, have investigated the role that growth factors play particularly in urologic tissues, both benign and malignant. We review several well-known growth factors and their function in prostate, kidney, and bladder tissues, as well as their functions in other regulating processes of the human body, and also the use of growth factors as tumor markers, and antibodies to growth factors as possible treatment of disease.

Evaluation and optimization of hepatocyte culture media factors by design of experiments (DoE) methodology

PubMed Central

Dong, Jia; Lübberstedt, Marc; Urbaniak, Thomas; Nüssler, Andreas K.N.; Knobeloch, Daniel; Gerlach, Jörg C.; Zeilinger, Katrin

2008-01-01

Optimization of cell culture media based on statistical experimental design methodology is a widely used approach for improving cultivation conditions. We applied this methodology to refine the composition of an established culture medium for growth of a human hepatoma cell line, C3A. A selection of growth factors and nutrient supplements were systematically screened according to standard design of experiments (DoE) procedures. The results of the screening indicated that the medium additives hepatocyte growth factor, oncostatin M, and fibroblast growth factor 4 significantly influenced the metabolic activities of the C3A cell line. Surface response methodology revealed that the optimum levels for these factors were 30 ng/ml for hepatocyte growth factor and 35 ng/ml for oncostatin M. Additional experiments on primary human hepatocyte cultures showed high variance in metabolic activities between cells from different individuals, making determination of optimal levels of factors more difficult. Still, it was possible to conclude that hepatocyte growth factor, epidermal growth factor, and oncostatin M had decisive effects on the metabolic functions of primary human hepatocytes. PMID:19003182

Evaluation and optimization of hepatocyte culture media factors by design of experiments (DoE) methodology.

PubMed

Dong, Jia; Mandenius, Carl-Fredrik; Lübberstedt, Marc; Urbaniak, Thomas; Nüssler, Andreas K N; Knobeloch, Daniel; Gerlach, Jörg C; Zeilinger, Katrin

2008-07-01

Optimization of cell culture media based on statistical experimental design methodology is a widely used approach for improving cultivation conditions. We applied this methodology to refine the composition of an established culture medium for growth of a human hepatoma cell line, C3A. A selection of growth factors and nutrient supplements were systematically screened according to standard design of experiments (DoE) procedures. The results of the screening indicated that the medium additives hepatocyte growth factor, oncostatin M, and fibroblast growth factor 4 significantly influenced the metabolic activities of the C3A cell line. Surface response methodology revealed that the optimum levels for these factors were 30 ng/ml for hepatocyte growth factor and 35 ng/ml for oncostatin M. Additional experiments on primary human hepatocyte cultures showed high variance in metabolic activities between cells from different individuals, making determination of optimal levels of factors more difficult. Still, it was possible to conclude that hepatocyte growth factor, epidermal growth factor, and oncostatin M had decisive effects on the metabolic functions of primary human hepatocytes.

Therapeutic angiogenesis: angiogenic growth factors for ischemic heart disease.

PubMed

Henning, Robert J

2016-09-01

Stem cells encode vascular endothelial growth factors (VEGFs), fibroblastic growth factors (FGFs), stem cell factor, stromal cell-derived factor, platelet growth factor and angiopoietin that can contribute to myocardial vascularization. VEGFs and FGFs are the most investigated growth factors. VEGFs regulate angiogenesis and vasculogenesis. FGFs stimulate vessel cell proliferation and differentiation and are regulators of endothelial cell migration, proliferation and survival. Clinical trials of VEGF or FGF for myocardial angiogenesis have produced disparate results. The efficacy of therapeutic angiogenesis can be improved by: (1) identifying the most optimal patients; (2) increased knowledge of angiogenic factor pharmacokinetics and proper dose; (3) prolonging contact of angiogenic factors with the myocardium; (4) increasing the efficiency of VEGF or FGF gene transduction; and (5) utilizing PET or MRI to measure myocardial perfusion and perfusion reserve.

Controllable mineral coatings on scaffolds as carriers for growth factor release for bone tissue engineering

NASA Astrophysics Data System (ADS)

Saurez-Gonzalez, Darilis

The work presented in this document, focused on the development and characterization of mineral coatings on scaffold materials to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite. FTIR data confirmed the substitution of HCO3 in the mineral. As the extent of HCO3 substitution increased, the coating exhibited more rapid dissolution kinetics in an environment deficient in calcium and phosphate. The mineral coatings provided an effective mechanism for bioactive growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral-coated PCL scaffolds. Recombinant human vascular endothelial growth factor (rhVEGF) also bound to mineral coated scaffolds with lower efficiency (20%) and released with faster release kinetics compared to peptides growth factor. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro and enhanced blood vessel formation in vivo in an intramuscular sheep model. In addition to the use the mineral coatings for single growth factor release, we expanded the concept and bound both an angiogenic (rhVEGF) and osteogenic (mBMP2) growth factor by a simple double dipping process. Sustained release of both growth factors was demonstrated for over 60 days. Released rhVEGF enhanced blood vessel formation in vivo in sheep and its biological activity was not affected by the presence of mBMP2. The approach for growth factor binding and release from mineral coatings can be adapted to different materials and medical devices and provide a simple and adaptable mechanism for sustained release of single or dual growth factors.

Growth factors and growth factor receptors in the hippocampus. Role in plasticity and response to injury.

PubMed

Nieto-Sampedro, M; Bovolenta, P

1990-01-01

Various growth factors are present in the hippocampal formation and appear responsible for the prominent plasticity of this brain area. Although hormone-like growth-promoting polypeptides are the best known, recent studies emphasize the importance in the growth response of molecules such as laminin proteoglycans, neurotransmitters and growth inhibitors. The progress and problems in the study of these substances are reviewed.

Trophic and neurotrophic factors in human pituitary adenomas (Review).

PubMed

Spoletini, Marialuisa; Taurone, Samanta; Tombolini, Mario; Minni, Antonio; Altissimi, Giancarlo; Wierzbicki, Venceslao; Giangaspero, Felice; Parnigotto, Pier Paolo; Artico, Marco; Bardella, Lia; Agostinelli, Enzo; Pastore, Francesco Saverio

2017-10-01

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.

Systemic review of dry socket: aetiology, treatment, and prevention.

PubMed

Tarakji, Bassel; Saleh, Lubna Ahmed; Umair, Ayesha; Azzeghaiby, Saleh Nasser; Hanouneh, Salah

2015-04-01

Our systemic review is to make a comprehensive review about the aetiology, treatment and the prevention of dry socket, the inclusion criteria were all the studies that discuss the dry socket and its etiology, treatment and prevention and exclusion criteria were all the studies that discuss the other complications of tooth extraction, the materials and methods used for this systemic review was to search in the Pub Medline database between 2008 to 2013, using specific words "dry socket, aetiology, treatment and prevention" and published in the English language, the articles were screened by abstract for relevance to aetiology, treatment and prevention of dry socket, 82 papers were identified in pub med but a total of 36 out of Publications were included in the final systemic review according to the specific keywords and materials mentioned above. The occurrence of dry socket in an everyday oral surgery or dental practice is unavoidable. The risk factors are smoking, surgical trauma, single extractions, age, sex, medical history, systemic disorder, extraction site, amount of anaesthesia, operator experience, antibiotics use prior to surgery, difficulty of the surgery and the previous surgical site infection in addition to oral Contraceptives, menstrual cycle and immediate postextraction socket irrigation with normal saline. The traditional options of treatment are directed toward palliative care, such as the irrigation of the surgical site, avoiding curetting the extraction socket, Packing with a zinc oxide- eugenol paste on iodoform gauze can be considered to relieve acute pain episodes, there is also new agents in the market can accelerate the healing of the socket such as PRGF and GECB. The prevention methods include avoiding smoking before and after surgery and a traumatic surgery, the use of antibiotics, such as, azithromycin, can be considered, the other preventive measures such as chlorhecidine rinse or gel can be effective in the reduction of dry socket incidence.

Systemic Review of Dry Socket: Aetiology, Treatment, and Prevention

PubMed Central

Saleh, Lubna Ahmed; Umair, Ayesha; Azzeghaiby, Saleh Nasser; Hanouneh, Salah

2015-01-01

Our systemic review is to make a comprehensive review about the aetiology, treatment and the prevention of dry socket, the inclusion criteria were all the studies that discuss the dry socket and its etiology, treatment and prevention and exclusion criteria were all the studies that discuss the other complications of tooth extraction, the materials and methods used for this systemic review was to search in the Pub Medline database between 2008 to 2013, using specific words “dry socket, aetiology, treatment and prevention” and published in the English language, the articles were screened by abstract for relevance to aetiology, treatment and prevention of dry socket, 82 papers were identified in pub med but a total of 36 out of Publications were included in the final systemic review according to the specific keywords and materials mentioned above. The occurrence of dry socket in an everyday oral surgery or dental practice is unavoidable. The risk factors are smoking, surgical trauma, single extractions, age, sex, medical history, systemic disorder, extraction site, amount of anaesthesia, operator experience, antibiotics use prior to surgery, difficulty of the surgery and the previous surgical site infection in addition to oral Contraceptives, menstrual cycle and immediate postextraction socket irrigation with normal saline. The traditional options of treatment are directed toward palliative care, such as the irrigation of the surgical site, avoiding curetting the extraction socket, Packing with a zinc oxide– eugenol paste on iodoform gauze can be considered to relieve acute pain episodes, there is also new agents in the market can accelerate the healing of the socket such as PRGF and GECB. The prevention methods include avoiding smoking before and after surgery and a traumatic surgery, the use of antibiotics, such as, azithromycin, can be considered, the other preventive measures such as chlorhecidine rinse or gel can be effective in the reduction of dry socket incidence. PMID:26023661

miR-24 and miR-122 Negatively Regulate the Transforming Growth Factor-β/Smad Signaling Pathway in Skeletal Muscle Fibrosis.

PubMed

Sun, Yaying; Wang, Hui; Li, Yan; Liu, Shaohua; Chen, Jiwu; Ying, Hao

2018-06-01

Fibrosis is common after skeletal muscle injury, undermining tissue regeneration and function. The mechanism underlying skeletal muscle fibrosis remains unveiled. Transforming growth factor-β/Smad signaling pathway is supposed to play a pivotal role. However, how microRNAs interact with transforming growth factor-β/Smad-related muscle fibrosis remains unclear. We showed that microRNA (miR)-24-3p and miR-122-5p declined in skeletal muscle fibrosis, which was a consequence of transforming growth factor-β. Upregulating Smad4 suppressed two microRNAs, whereas inhibiting Smad4 elevated microRNAs. Luciferase reporter assay and chromatin immunoprecipitation confirmed that Smad4 directly inhibited two microRNAs. On the other hand, overexpression of these two miRs retarded fibrotic process. We further identified that Smad2 was a direct target of miR-24-3p, whereas miR-122-5p targeted transforming growth factor-β receptor-II. Both targets were important participants in transforming growth factor-β/Smad signaling. Taken together, a positive feedback loop in transforming growth factor-β/Smad4 signaling pathway in skeletal muscle fibrosis was identified. Transforming growth factor-β/Smad axis could be downregulated by microRNAs. This effect, however, was suppressed by Smad4, the downstream of transforming growth factor-β. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

PubMed Central

Arrieta, O; Guevara, P; Escobar, E; García-Navarrete, R; Pineda, B; Sotelo, J

2005-01-01

Angiotensin II (Ang II) is a main effector peptide in the renin–angiotensin system and participates in the regulation of vascular tone. It also has a role in the expression of growth factors that induce neovascularisation which is closely associated to the growth of malignant gliomas. We have shown that the selective blockage of the AT1 receptor of angiotensin inhibites tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT1 receptor on the synthesis of growth factors, and in the genesis of apoptosis in cultured C6 glioma cells and in rats with C6 glioma. Administration of losartan at doses of 40 or 80 mg kg−1 to rats with C6 glioma significantly decreased tumoral volume and production of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dose-dependent manner. Administration of Ang II increased cell proliferation of cultured C6 cells which decreased by the administration of losartan. Our results suggest that the selective blockage of AT1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis. PMID:15785746

78 FR 45208 - Children's Health Insurance Program (CHIP); Final Allotments to States, the District of Columbia...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-26

... Health Care Growth (PCHCG) Factor for FY 2013, determined as 1 plus the percentage increase in the Per... expenditures under an approved state child health plan for 2 fiscal years, including the year for which the... care growth factor and the child population growth factor. The per capita health care growth factor for...

ROLES OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF-A) IN MEDIATION OF DIOXIN (TCDD)-INDUCED DELAYS IN DEVELOPMENT OF THE MOUSE MAMMARY GLAND

EPA Science Inventory

Roles of Epidermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-a) in Mediation of Dioxin (TCDD)-Induced Delays in Development of the Mouse Mammary Gland.
Suzanne E. Fenton, Barbara Abbott, Lamont Bryant, and Angela Buckalew. U.S. EPA, NHEERL, Reproductive Tox...

Synthetic heparin-binding growth factor analogs

DOEpatents

Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

2007-01-23

The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1.

PubMed

Mooney, R A; Freund, G G; Way, B A; Bordwell, K L

1992-11-25

Tyrosine phosphorylation is a mechanism of signal transduction shared by many growth factor receptors and oncogene products. Phosphotyrosine phosphatases (PTPases) potentially modulate or counter-regulate these signaling pathways. To test this hypothesis, the transmembrane PTPase CD45 (leukocyte common antigen) was expressed in the murine cell line C127. Hormone-dependent autophosphorylation of the platelet-derived growth factor (PDGF) and insulin-like growth factor-1 (IGF-1) receptors was markedly reduced in cells expressing the transmembrane PTPase. Tyrosine phosphorylation of other PDGF-dependent phosphoproteins (160, 140, and 55 kDa) and IGF-1-dependent phosphoproteins (145 kDa) was similarly decreased. Interestingly, the pattern of growth factor-independent tyrosine phosphorylations was comparable in cells expressing the PTPase and control cells. This suggests a selectivity or accessibility of the PTPase limited to a subset of cellular phosphotyrosyl proteins. The maximum mitogenic response to PDGF and IGF-1 in cells expressing the PTPase was decreased by 67 and 71%, respectively. These results demonstrate that a transmembrane PTPase can both affect the tyrosine phosphorylation state of growth factor receptors and modulate proximal and distal cellular responses to the growth factors.

Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

PubMed

Selheim, F; Holmsen, H; Vassbotn, F S

1999-08-15

We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

Growth factors, nutrient signaling, and cardiovascular aging

PubMed Central

Fontana, Luigi; Vinciguerra, Manlio; Longo, Valter D.

2012-01-01

Growth factors regulated by specific macronutrients have been shown to promote aging and accelerate mortality in the great majority of the organisms studied. In particular, the enzymes activated by growth hormone (GH), insulin and insulin-like growth factor 1 (IGF-I) in mammals and their orthologs in simple model organisms represent perhaps the best-understood proteins involved in the aging process. Dietary restriction (DR), which reduces the level of IGF-I and of other growth factors, has been associated with protection from diabetes, cancer, and cardiovascular diseases and deficiencies in GH signaling and IGF-I are strongly associated with protection from cancer and diabetes in both mice and humans, but their role in cardiac function and cardiovascular diseases is controversial. Here we review the link between growth factors, cardiac function and heart disease with focus on the cardioprotective and sensitizing effect of growth factors in both model organisms and humans. PMID:22499903

Insulin-like growth factor I (IGF-1) Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

PubMed

Schlegel, Werner; Raimann, Adalbert; Halbauer, Daniel; Scharmer, Daniela; Sagmeister, Susanne; Wessner, Barbara; Helmreich, Magdalena; Haeusler, Gabriele; Egerbacher, Monika

2013-01-01

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

PubMed Central

Schlegel, Werner; Raimann, Adalbert; Halbauer, Daniel; Scharmer, Daniela; Sagmeister, Susanne; Wessner, Barbara; Helmreich, Magdalena; Haeusler, Gabriele; Egerbacher, Monika

2013-01-01

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation. PMID:24146828

A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

NASA Astrophysics Data System (ADS)

Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

1995-10-01

Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

Skin problems and EGFR-tyrosine kinase inhibitor.

PubMed

Kozuki, Toshiyuki

2016-04-01

Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montesano, Roberto; Sarkoezi, Rita; Schramek, Herbert

2008-09-12

Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hithertomore » unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.« less

Isolation of a cDNA for a Growth Factor of Vascular Endothelial Cells from Human Lung Cancer Cells: Its Identity with Insulin‐like Growth Factor II

PubMed Central

Hagiwara, Koichi; Kobayashi, Tatsuo; Tobita, Masato; Kikyo, Nobuaki; Yazaki, Yoshio

1995-01-01

We have found growth‐promoting activity for vascular endothelial cells in the conditioned medium of a human lung cancer cell line, T3M‐11. Purification and characterization of the growth‐promoting activity have been carried out using ammonium sulfate precipitation and gel‐exclusion chromatography. The activity migrated as a single peak just after ribonuclease. It did not bind to a heparin affinity column. These results suggest that the activity is not a heparin‐binding growth factor (including fibroblast growth factors) or a vascular endothelial growth factor. To identify the molecule exhibiting the growth‐promoting activity, a cDNA encoding the growth factor was isolated through functional expression cloning in COS‐1 cells from a cDNA library prepared from T3M‐11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with that of insulin‐like growth factor II. PMID:7730145

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

PubMed

Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

2017-01-01

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

Growth factor transgenes interactively regulate articular chondrocytes.

PubMed

Shi, Shuiliang; Mercer, Scott; Eckert, George J; Trippel, Stephen B

2013-04-01

Adult articular chondrocytes lack an effective repair response to correct damage from injury or osteoarthritis. Polypeptide growth factors that stimulate articular chondrocyte proliferation and cartilage matrix synthesis may augment this response. Gene transfer is a promising approach to delivering such factors. Multiple growth factor genes regulate these cell functions, but multiple growth factor gene transfer remains unexplored. We tested the hypothesis that multiple growth factor gene transfer selectively modulates articular chondrocyte proliferation and matrix synthesis. We tested the hypothesis by delivering combinations of the transgenes encoding insulin-like growth factor I (IGF-I), fibroblast growth factor-2 (FGF-2), transforming growth factor beta1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), and bone morphogenetic protien-7 (BMP-7) to articular chondrocytes and measured changes in the production of DNA, glycosaminoglycan, and collagen. The transgenes differentially regulated all these chondrocyte activities. In concert, the transgenes interacted to generate widely divergent responses from the cells. These interactions ranged from inhibitory to synergistic. The transgene pair encoding IGF-I and FGF-2 maximized cell proliferation. The three-transgene group encoding IGF-I, BMP-2, and BMP-7 maximized matrix production and also optimized the balance between cell proliferation and matrix production. These data demonstrate an approach to articular chondrocyte regulation that may be tailored to stimulate specific cell functions, and suggest that certain growth factor gene combinations have potential value for cell-based articular cartilage repair. Copyright © 2012 Wiley Periodicals, Inc.

Growth factor involvement in tension-induced skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.

1993-01-01

Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

Insulin-like growth factors and insulin: at the crossroad between tumor development and longevity.

PubMed

Novosyadlyy, Ruslan; Leroith, Derek

2012-06-01

Numerous lines of evidence indicate that insulin-like growth factor signaling plays an important role in the regulation of life span and tumor development. In the present paper, the role of individual components of insulin-like growth factor signaling in aging and tumor development has been extensively analyzed. The molecular mechanisms underlying aging and tumor development are frequently overlapping. Although the link between reduced insulin-like growth factor signaling and suppressed tumor growth and development is well established, it remains unclear whether extended life span results from direct suppression of insulin-like growth factor signaling or this effect is caused by indirect mechanisms such as improved insulin sensitivity.

Epidermal growth factor in alkali-burned corneal epithelial wound healing.

PubMed

Singh, G; Foster, C S

1987-06-15

We conducted a double-masked study to evaluate the effect of epidermal growth factor on epithelial wound healing and recurrent erosions in alkali-burned rabbit corneas. Epithelial wounds 10 mm in diameter healed completely under the influence of topical epidermal growth factor, whereas the control corneas did not resurface in the center. On reversal of treatment, the previously nonhealing epithelial defects healed when treated with topical epidermal growth factor eyedrops. Conversely, the epidermal growth factor-treated and resurfaced corneas developed epithelial defects when treatment was discontinued. Histopathologic examination disclosed hyperplastic epithelium growing over the damaged stroma laden with polymorphonuclear leukocytes when treated with epidermal growth factor eyedrops, but it did not adhere to the underlying tissue. Hydropic changes were seen intracellularly as well as between the epithelial cells and the stroma.

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation

PubMed Central

Gaviglio, Angela L.; Knelson, Erik H.; Blobe, Gerard C.

2017-01-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor–like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.—Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. PMID:28174207

Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

PubMed Central

Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

2014-01-01

Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

The future of recombinant growth factors in wound healing.

PubMed

Robson, M C; Mustoe, T A; Hunt, T K

1998-08-01

For more than a decade, clinical trials have been conducted of the application of topical exogenous recombinant growth factors in attempts to accelerate the healing of chronic wounds. Although the results of some of these trials have been encouraging, overall the results have been somewhat discouraging. Much of the difficulty lies in the paucity of carefully controlled clinical trials of wound healing. Since wound healing is a complex process that can be influenced, both positively and negatively, by many factors, designing these trials has proved difficult. To date, only a single recombinant growth factor-recombinant human platelet-derived growth factor-BB (rhPDGF-BB)- has been approved by the US Food and Drug Administration; and that only for use in diabetic foot ulcers. It is unlikely, however, that a single growth factor will be able to resolve all issues of repair or strengthen all vulnerabilities of chronic wounds. Our expectation, therefore, is that growth factors, cytokines, and other biologic agents will be used more specifically in the future, for example, by targeting growth factor therapy at those specific components or processes that a given wound uses to heal.

In vivo hair growth-promoting effect of rice bran extract prepared by supercritical carbon dioxide fluid.

PubMed

Choi, Jae-Suk; Jeon, Min-Hee; Moon, Woi-Sook; Moon, Jin-Nam; Cheon, Eun Jin; Kim, Joo-Wan; Jung, Sung Kyu; Ji, Yi-Hwa; Son, Sang Wook; Kim, Mi-Ryung

2014-01-01

The potential hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and major components of RB-SCE, linoleic acid, policosanol, γ-oryzanol, and γ-tocotrienol, were evaluated with the histological morphology and mRNA expression levels of cell growth factors using real-time reverse transcriptase-polymerase chain reaction (PCR) in C57BL/6 mice. RB-SCE showed hair growth-promoting potential to a similar extent as 3% minoxidil, showing that the hair follicles were induced to be in the anagen stage. The numbers of the hair follicles were significantly increased. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and keratinocyte growth factor (KGF) were also significantly increased and that of transforming growth factor-β (TGF-β) decreased in RB-SCE-treated groups. Among the major components of RB-SCE, linoleic acid and γ-oryzanol induced the formation of hair follicles according to examination of histological morphology and mRNA expression levels of cell growth factors. In conclusion, our results demonstrate that RB-SCE, particularly linoleic acid and γ-oryzanol, promotes hair growth and suggests RB-SCE can be applied as hair loss treatment.

Angiogenesis inhibitors: current strategies and future prospects.

PubMed

Cook, Kristina M; Figg, William D

2010-01-01

Angiogenesis has become an attractive target for drug therapy because of its key role in tumor growth. An extensive array of compounds is currently in preclinical development, with many now entering the clinic and/or achieving approval from the US Food and Drug Administration. Several regulatory and signaling molecules governing angiogenesis are of interest, including growth factors (eg, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor), receptor tyrosine kinases, and transcription factors such as hypoxia inducible factor, as well as molecules involved in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling. Pharmacologic agents have been identified that target these pathways, yet for some agents (notably thalidomide), an understanding of the specific mechanisms of antitumor action has proved elusive. The following review describes key molecular mechanisms and novel therapies that are on the horizon for antiangiogenic tumor therapy. (c) 2010 American Cancer Society, Inc.

Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis

DTIC Science & Technology

2008-10-01

AD_________________ AWARD NUMBER: W81XWH-06-1-0763 TITLE: Role of Fibroblast Growth Factor ...Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis 5b. GRANT NUMBER W81XWH-06-1-0763 5c. PROGRAM...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Fibroblast growth factors (FGFs) are vital modulators of development as well as

Factors That Influence Language Growth.

ERIC Educational Resources Information Center

McCarthy, Dorothea, Ed.; And Others

This booklet contains four articles that discuss factors influencing language growth. The first, "The Child's Equipment for Language Growth" by Charlotte Wells, examines what the child needs for language learning, how the child uses his equipment for language growth, and what school factors facilitate the child's use of his equipment for language…

Selenoprotein W controls epidermal growth factor receptor surface expression, activation and degradation via receptor ubiquitination

USDA-ARS?s Scientific Manuscript database

Epidermal growth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of growth factor receptors that modulate a complex network of intracellular signaling pathways controlling growth, proliferation and differentiation. Selenoprotein W (SEPW1) is a diet-regulated, highly conserved...

Identification of interleukin-6 as an autocrine growth factor for Epstein-Barr virus-immortalized B cells.

PubMed Central

Tosato, G; Tanner, J; Jones, K D; Revel, M; Pike, S E

1990-01-01

Autocrine growth factors are believed to be important for maintenance of an immortalized state by Epstein-Barr virus (EBV), because cell-free supernatants of EBV-immortalized cell lines promote the proliferation of autologous cells and permit their growth at low cell density. In this study, we provide evidence for the existence of two autocrine growth factor activities produced by EBV-immortalized lines distinguished by size and biological activities. Much of the autocrine growth factor activity in lymphoblastoid cell line supernatants resided in a low-molecular-weight (less than 5,000) fraction. However, up to 20 to 30% of the autocrine growth factor activity resided in the high-molecular-weight (greater than 5,000) fraction. While the nature of the low-molecular-weight growth factor activity remains undefined, the high-molecular-weight growth factor activity was identified as interleukin-6 (IL-6). Culture supernatants from six EBV-induced lymphoblastoid cell lines tested contained IL-6 activity, because they promoted proliferation in the IL-6-dependent hybridoma cell line B9. In addition, a rabbit antibody to human IL-6 neutralized the capacity of the high-molecular-weight (greater than 5,000) fraction of a lymphoblastoid cell line supernatant to promote growth both in autologous EBV-immortalized cells and in B9 cells. Similarly, this high-molecular-weight autocrine growth factor activity was neutralized by a monoclonal antibody to human IL-6. Furthermore, characteristic bands, attributable to IL-6, were visualized in supernatants of each of four EBV-induced lymphoblastoid cell lines after immunoprecipitation with a rabbit antiserum to human IL-6. Thus, in addition to its previously reported properties, IL-6 is an autocrine growth factor for EBV-immortalized B cells cultured under serum-free conditions. Images PMID:2159561

EGFR Ligands Drive Multipotential Stromal Cells to Produce Multiple Growth Factors and Cytokines via Early Growth Response-1

PubMed Central

Kerpedjieva, Svetoslava S.; Kim, Duk Soo; Barbeau, Dominique J.

2012-01-01

Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)–EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase–extracellular-signal-regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin-binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands. PMID:22316125

EGFR ligands drive multipotential stromal cells to produce multiple growth factors and cytokines via early growth response-1.

PubMed

Kerpedjieva, Svetoslava S; Kim, Duk Soo; Barbeau, Dominique J; Tamama, Kenichi

2012-09-01

Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)-EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase-extracellular-signal-regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin-binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands.

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia.

PubMed

Moises, Hans W; Zoega, Tomas; Gottesman, Irving I

2002-07-03

A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments.

Heparin Microparticle Effects on Presentation and Bioactivity of Bone Morphogenetic Protein-2

PubMed Central

Hettiaratchi, Marian H.; Miller, Tobias; Temenoff, Johnna S.; Guldberg, Robert E.; McDevitt, Todd C.

2014-01-01

Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration. PMID:24881028

Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

PubMed

Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

2014-01-01

In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001), TGF-β1 (r=0.85, p<0.001), VEGF (r=0.46, p<0.01) and PDGF-bb (r=0.9, p<0.001). Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

Mitogenic signaling pathways of growth factors can be distinguished by the involvement of pertussis toxin-sensitive guanosine triphosphate-binding protein and of protein kinase C.

PubMed Central

Nishizawa, N; Okano, Y; Chatani, Y; Amano, F; Tanaka, E; Nomoto, H; Nozawa, Y; Kohno, M

1990-01-01

We have examined the possible involvements of pertussis toxin (PT)-sensitive guanosine triphosphate (GTP)-binding protein (Gp) and protein kinase C (PKC) in the mitogenic signaling pathways of various growth factors by the use of PT-pretreated and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA)-pretreated mouse fibroblasts. Effects of PT pretreatment (inactivation of PT-sensitive Gp) and TPA pretreatment (depletion of PKC) on mitogen-induced DNA synthesis varied significantly and systematically in response to growth factors: mitogenic responses of cells to thrombin, bombesin, and bradykinin were almost completely abolished both in PT- and TPA-pretreated cells; responses to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vanadate were reduced to approximately 50% both in PT- and TPA-pretreated cells compared with native cells; response to basic fibroblast growth factor (bFGF) was not affected in PT-pretreated cells but was inhibited to some extent in TPA-pretreated cells. Thus, growth factors examined have been classified into three groups with regard to the involvements of PT-sensitive Gp and PKC in their signal transduction pathways. Binding of each growth factor to its receptor was not affected significantly by pretreatment of cells with PT or TPA. Inhibitory effects of PT and TPA pretreatment on each mitogen-induced DNA synthesis were not additive, suggesting that the functions of PT-sensitive Gp and PKC lie on an identical signal transduction pathway. Although all three groups of mitogens activated PKC, signaling of each growth factor depends to a varying extent on the function of PKC. Our results indicate that a single peptide growth factor such as EGF, PDGF, or bFGF acts through multiple signaling pathways to induce cell proliferation. Images PMID:2129194

Preclinical and clinical studies on the use of growth factors for bone repair: a systematic review.

PubMed

Fisher, Daniel Mark; Wong, James Min-Leong; Crowley, Conor; Khan, Wasim S

2013-05-01

Bone healing is a complex process. Whilst the majority of fractures heal with conventional treatment, open fractures, large bone defects and non unions still provide great challenges to Orthopaedic Surgeons. Whilst autologous bone graft is seen as the gold standard, the use of growth factors is a growing area of research to find an effective alternative with lower side effects such as donor site morbidity and the finite amount available. This systematic review aims to summarize the pre clinical in-vivo studies and examine the clinical studies on the use of growth factors in bone healing. Databases: PubMed, Medline, OVID, and Cochrane library. The following key words and search terms were used: Growth Factors, Bone Healing, Bone Morphogenic Protein, Transforming Growth Factor Beta, Insulin Like Growth Factor, Platelet Derived Growth Factor, Fracture. All articles were screened based on title with abstracts and full text articles reviewed as appropriate. Reference lists were reviewed from relevant articles to ensure comprehensive and systematic review. Three tables of studies were constructed focussing on Bone Morphogenic Proteins, Platelet Rich Plasma and Growth Factors and Tissue Engineering. Bone Morphogenic Proteins and Platelet Rich Plasma, which contains multiple growth factors, have been shown in preclinical and clinical trials to be an effective alternative to autologous bone graft. Bone Morphogenic Proteins have been shown to be effective in fracture non union, and in open tibial fractures. Platelet Rich Plasma has shown promise in preclinical trials and some small clinical trials, however numbers are limited. Bone Morphogenic Proteins have been shown to be superior to Platelet Rich Protein in one trial. Combining these growth factors with tissue engineering techniques is the focus of ongoing research, and through further clinical trials the most effective techniques for enhancing bone healing will be revealed.

The ubiquitin ligase Nedd4 mediates oxidized low-density lipoprotein-induced downregulation of insulin-like growth factor-1 receptor

PubMed Central

Higashi, Yusuke; Sukhanov, Sergiy; Parthasarathy, Sampath; Delafontaine, Patrice

2008-01-01

Oxidized low-density lipoprotein (LDL) is proatherogenic and induces smooth muscle cell apoptosis, which contributes to atherosclerotic plaque destabilization. We showed previously that oxidized LDL downregulates insulin-like growth factor-1 receptor in human smooth muscle cells and that this is critical for induction of apoptosis. To identify mechanisms, we exposed smooth muscle cells to 60 μg/ml oxidized LDL or native LDL and assessed insulin-like growth factor-1 receptor mRNA levels, protein synthesis rate, and receptor protein stability. Oxidized LDL decreased insulin-like growth factor-1 receptor mRNA levels by 30% at 8 h compared with native LDL, and this decrease was maintained for up to 20 h. However, insulin-like growth factor-1 receptor protein synthesis rate was not altered by oxidized LDL. Pulse-chase labeling experiments revealed that oxidized LDL reduced insulin-like growth factor-1 receptor protein half-life to 12.2 ± 1.7 h from 24.4 ± 4.7 h with native LDL. This destabilization of insulin-like growth factor-1 receptor protein was accompanied by enhanced receptor ubiquitination. Overexpression of dominant-negative Nedd4 prevented oxidized LDL-induced downregulation of insulin-like growth factor-1 receptor, suggesting that Nedd4 was the ubiquitin ligase that mediated receptor downregulation. However, the proteasome inhibitors lactacystin, MG-132, and proteasome inhibitor-1 failed to block oxidized LDL-induced downregulation of insulin-like growth factor-1 receptor. Thus oxidized LDL downregulates insulin-like growth factor-1 receptor by destabilizing the protein via Nedd4-enhanced ubiquitination, leading to degradation via a proteasome-independent pathway. This finding provides novel insights into oxidized LDL-triggered oxidant signaling and mechanisms of smooth muscle cell depletion that contribute to plaque destabilization and coronary events. PMID:18723765

Clinical Applications of Platelet-Rich Plasma in Patellar Tendinopathy

PubMed Central

Jeong, D. U.; Lee, C.-R.; Lee, J. H.; Pak, J.; Kang, L.-W.; Jeong, B. C.

2014-01-01

Platelet-rich plasma (PRP), a blood derivative with high concentrations of platelets, has been found to have high levels of autologous growth factors (GFs), such as transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), fibroblastic growth factor (FGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). These GFs and other biological active proteins of PRP can promote tissue healing through the regulation of fibrosis and angiogenesis. Moreover, PRP is considered to be safe due to its autologous nature and long-term usage without any reported major complications. Therefore, PRP therapy could be an option in treating overused tendon damage such as chronic tendinopathy. Here, we present a systematic review highlighting the clinical effectiveness of PRP injection therapy in patellar tendinopathy, which is a major cause of athletes to retire from their respective careers. PMID:25136568

Increased plasma FGF21 level as an early biomarker for insulin resistance and metabolic disturbance in obese insulin-resistant rats.

PubMed

Tanajak, Pongpan; Pongkan, Wanpitak; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2018-05-01

Propose: To investigate the temporal relationship between plasma fibroblast growth factor 21 levels, insulin resistance, metabolic dysfunction and cardiac fibroblast growth factor 21 resistance in long-term high-fat diet-induced obese rats. In total, 36 male Wistar rats were fed with either a normal diet or high-fat diet for 12 weeks. Blood was collected from the tail tip, and plasma was used to determine metabolic profiles and fibroblast growth factor 21 levels. Rats were sacrificed at weeks 4, 8 and 12, and the hearts were rapidly removed for the determination of cardiac fibroblast growth factor 21 signalling pathways. Body weight and plasma fibroblast growth factor 21 levels were increased after 4 weeks of consumption of a high-fat diet. At weeks 8 and 12, high-fat diet rats had significantly increased body weight and plasma fibroblast growth factor 21 levels, together with increased plasma insulin, HOMA index, area under the curve of glucose, plasma total cholesterol, plasma low-density lipoprotein cholesterol, serum malondialdehyde and cardiac malondialdehyde levels. However, plasma high-density lipoprotein cholesterol levels and cardiac fibroblast growth factor 21 signalling proteins (p-FGFR1 Tyr 154 , p-ERK1/2 Thr 202 /Tyr 204 and p-Akt Ser 473 ) were decreased, compared with normal diet rats. These findings suggest that plasma fibroblast growth factor 21 levels could be an early predictive biomarker prior to the development of insulin resistance, metabolic disturbance and cardiac fibroblast growth factor 21 resistance.

Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo

NASA Astrophysics Data System (ADS)

Kim, K. Jin; Li, Bing; Winer, Jane; Armanini, Mark; Gillett, Nancy; Phillips, Heidi S.; Ferrara, Napoleone

1993-04-01

THE development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation1,2. Blood vessel neoformation is also important in the pathogenesis of many disorders1-5, particularly rapid growth and metastasis of solid tumours3-5. There are several potential mediators of tumour angiogenesis, including basic and acidic fibroblast growth factors, tumour necrosis factor-α and transforming factors-α and -β 1,2. But it is unclear whether any of these agents actually mediates angiogenesis and tumour growth in vivo. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenesis inducer released by a variety of tumour cells and expressed in human tumours in situ. To test whether VEGF may be a tumour angiogenesis factor in vivo, we injected human rhabdomyosar-coma, glioblastoma multiforme or leiomyosarcoma cell lines into nude mice. We report here that treatment with a monoclonal antibody specific for VEGF inhibited the growth of the tumours, but had no effect on the growth rate of the tumour cells In vitro. The density of vessels was decreased in the antibody-treated tumours. These findings demonstrate that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.

Analysis of the Effects of Five Factors Relevant to In Vitro Chondrogenesis of Human Mesenchymal Stem Cells Using Factorial Design and High Throughput mRNA-Profiling

PubMed Central

Jakobsen, Rune B.; Østrup, Esben; Zhang, Xiaolan; Mikkelsen, Tarjei S.; Brinchmann, Jan E.

2014-01-01

The in vitro process of chondrogenic differentiation of mesenchymal stem cells for tissue engineering has been shown to require three-dimensional culture along with the addition of differentiation factors to the culture medium. In general, this leads to a phenotype lacking some of the cardinal features of native articular chondrocytes and their extracellular matrix. The factors used vary, but regularly include members of the transforming growth factor β superfamily and dexamethasone, sometimes in conjunction with fibroblast growth factor 2 and insulin-like growth factor 1, however the use of soluble factors to induce chondrogenesis has largely been studied on a single factor basis. In the present study we combined a factorial quality-by-design experiment with high-throughput mRNA profiling of a customized chondrogenesis related gene set as a tool to study in vitro chondrogenesis of human bone marrow derived mesenchymal stem cells in alginate. 48 different conditions of transforming growth factor β 1, 2 and 3, bone morphogenetic protein 2, 4 and 6, dexamethasone, insulin-like growth factor 1, fibroblast growth factor 2 and cell seeding density were included in the experiment. The analysis revealed that the best of the tested differentiation cocktails included transforming growth factor β 1 and dexamethasone. Dexamethasone acted in synergy with transforming growth factor β 1 by increasing many chondrogenic markers while directly downregulating expression of the pro-osteogenic gene osteocalcin. However, all factors beneficial to the expression of desirable hyaline cartilage markers also induced undesirable molecules, indicating that perfect chondrogenic differentiation is not achievable with the current differentiation protocols. PMID:24816923

Cross-talk between GPER and growth factor signaling.

PubMed

Lappano, Rosamaria; De Marco, Paola; De Francesco, Ernestina Marianna; Chimento, Adele; Pezzi, Vincenzo; Maggiolini, Marcello

2013-09-01

G protein-coupled receptors (GPCRs) and growth factor receptors mediate multiple physio-pathological responses to a diverse array of extracellular stimuli. In this regard, it has been largely demonstrated that GPCRs and growth factor receptors generate a multifaceted signaling network, which triggers relevant biological effects in normal and cancer cells. For instance, some GPCRs transactivate the epidermal growth factor receptor (EGFR), which stimulates diverse transduction pathways leading to gene expression changes, cell migration, survival and proliferation. Moreover, it has been reported that a functional interaction between growth factor receptors and steroid hormones like estrogens is involved in the growth of many types of tumors as well as in the resistance to endocrine therapy. This review highlights recent findings on the cross-talk between a member of the GPCR family, the G protein-coupled estrogen receptor 1 (GPER, formerly known as GPR30) and two main growth factor receptors like EGFR and insulin-like growth factor-I receptor (IGF-IR). The biological implications of the functional interaction between these important mediators of cell responses particularly in cancer are discussed. This article is part of a Special Issue entitled 'CSR 2013'. Copyright © 2013 Elsevier Ltd. All rights reserved.

EFFECTS OF EPIDERMAL GROWTH FACTOR (EGF), TRANSFORMING GROWTH FACTOR- (TGF), AND 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ON FUSION OF EMBRYONIC PALATES IN SERUM-FREE ORGAN CULTURE USING WILD-TYPE, EGF KNOCKOUT, AND TGF KNOCKOUT MOUSE STRAINS

EPA Science Inventory

Backround: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, producing cleft palate (CP). TCDD exposure disrupts expression of epidermal growth factor (EGF) receptor, EGF, and transforming growth factor- (TGF) in the palate and affects proliferation and different...

In vitro propagation of male germline stem cells from piglets.

PubMed

Zheng, Yi; Tian, Xiue; Zhang, Yaqing; Qin, Jinzhou; An, Junhui; Zeng, Wenxian

2013-07-01

To study the effects of serum and growth factors on propagation of porcine male germline stem cells (MGSCs) in vitro and develop a culture system for these stem cells. Fresh testicular cells from neonatal piglets were obtained by mechanical dissociation and collagenase-trypsin digestion. After differential plating, non-adhering cells were cultured in media supplemented with different concentrations of serum (0, 1 %, 2 %, 5 %, 10 %). After 10 days of primary culture, the cells were maintained in media supplemented with different concentrations of growth factors (basic fibroblast growth factor and epidermal growth factor at 1, 5, 10 ng/ml). The number of MGSC-derived colonies with different sizes was determined in each treatment to assess the effects of serum concentrations and growth factors. The number of MGSC-derived colonies was significantly higher in the presence of 1 % rather than 10 % fetal bovine serum (FBS). Basic fibroblast growth factor (bFGF) at 1, 5 ng/ml and epidermal growth factor (EGF) at 5, 10 ng/ml significantly promoted colony formation. Immunocytochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and xenotransplantation assays demonstrated the presence of functional stem cells in cultured cell population. In vitro propagation of porcine MGSCs could be maintained in the presence of 1 % FBS and supplementation of growth factors for 1 month.

The neurotrophins act synergistically with LIF and members of the TGF-beta superfamily to promote the survival of spiral ganglia neurons in vitro.

PubMed

Marzella, P L; Gillespie, L N; Clark, G M; Bartlett, P F; Kilpatrick, T J

1999-12-01

A number of growth factor families have been implicated in normal inner ear development, auditory neuron survival and protection. Several growth factors, including transforming growth factor-beta5 (TGF-beta5) and TGF-beta3, neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were tested for their ability, individually or in combination, to promote auditory neuron survival in dissociated cell cultures of early rat post-natal spiral ganglion cells (SGCs). The results indicate that at discrete concentrations all growth factors act in an additive fashion and some in synergy when promoting neuronal survival. These findings support the hypothesis that growth factors from different families may be interdependent when sustaining neuronal integrity.

Research on growth factors in periodontology.

PubMed

Smith, Patricio C; Martínez, Constanza; Cáceres, Mónica; Martínez, Jorge

2015-02-01

Growth factors play critical roles in periodontal repair through the regulation of cell behavior. Many of the cell responses regulated by these proteins include cell adhesion, migration, proliferation and differentiation. Periodontal regeneration involves an organized response of different cells, tissues and growth factors implicated in the coordination of these events. However, periodontal tissue reconstruction is an extremely difficult task. Multiple studies have been performed to understand the specific role of growth factors in periodontal wound healing. In the present review we analyze the evidence that supports the roles of growth factors in periodontal wound healing and regeneration. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.

PubMed

Rehman, Jalees; Li, Jingling; Orschell, Christie M; March, Keith L

2003-03-04

Endothelial progenitor cells (EPCs) have been isolated from peripheral blood and can enhance angiogenesis after infusion into host animals. It is not known whether the proangiogenic effects are a result of such events as endothelial differentiation and subsequent proliferation of EPCs or secondary to secretion of angiogenic growth factors. Human EPCs were isolated as previously described, and their phenotypes were confirmed by uptake of acetylated LDL and binding of ulex-lectin. EPC proliferation and surface marker expression were analyzed by flow cytometry, and conditioned medium was assayed for growth factors. The majority of EPCs expressed monocyte/macrophage markers such as CD14 (95.7+/-0.3%), Mac-1 (57.6+/-13.5%), and CD11c (90.8+/-4.9%). A much lower percentage of cells expressed the specific endothelial marker VE-cadherin (5.2+/-0.7%) or stem/progenitor-cell markers AC133 (0.16+/-0.05%) and c-kit (1.3+/-0.7%). Compared with circulating monocytes, cultured EPCs showed upregulation of monocyte activation and macrophage differentiation markers. EPCs did not demonstrate any significant proliferation but did secrete the angiogenic growth factors vascular endothelial growth factor, hepatocyte growth factor, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Our findings suggest that acetylated LDL(+)ulex-lectin(+) cells, commonly referred to as EPCs, do not proliferate but release potent proangiogenic growth factors. The majority of acetylated LDL(+)ulex-lectin(+) cells are derived from monocyte/macrophages. The findings of low proliferation and endothelial differentiation suggest that their angiogenic effects are most likely mediated by growth factor secretion. These findings may allow for development of novel angiogenic therapies relying on secreted growth factors or on recruitment of endogenous monocytes/macrophages to sites of ischemia.

Endorsement of Growth Factors in Experiential Training Groups

ERIC Educational Resources Information Center

Kiweewa, John; Gilbride, Dennis; Luke, Melissa; Seward, Derek

2013-01-01

The purpose of this study was to identify student growth factors during a semester long Master's level group counseling class. Results indicated that 12 growth factors accounted for 86% of the total number of critical incidents that participants reported as influencing their personal growth and awareness during the group experience. Two other…

Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

DTIC Science & Technology

2010-10-01

AD_________________ Award Number: W81XWH-08-1-0708 TITLE: Fibroblast Growth Factor 2: an...September 2009 – 14 September 2010 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fibroblast Growth Factor 2: an Epithelial Ductal Cell Growth ...8 Appendices…………………………………………………………………………… 8 Supporting Data……………………………………………………………………... 8 Fibroblast Growth Factor -2: an

Cartilage Engineering from Mesenchymal Stem Cells

NASA Astrophysics Data System (ADS)

Goepfert, C.; Slobodianski, A.; Schilling, A. F.; Adamietz, P.; Pörtner, R.

Mesenchymal progenitor cells known as multipotent mesenchymal stromal cells or mesenchymal stem cells (MSC) have been isolated from various tissues. Since they are able to differentiate along the mesenchymal lineages of cartilage and bone, they are regarded as promising sources for the treatment of skeletal defects. Tissue regeneration in the adult organism and in vitro engineering of tissues is hypothesized to follow the principles of embryogenesis. The embryonic development of the skeleton has been studied extensively with respect to the regulatory mechanisms governing morphogenesis, differentiation, and tissue formation. Various concepts have been designed for engineering tissues in vitro based on these developmental principles, most of them involving regulatory molecules such as growth factors or cytokines known to be the key regulators in developmental processes. Growth factors most commonly used for in vitro cultivation of cartilage tissue belong to the fibroblast growth factor (FGF) family, the transforming growth factor-beta (TGF-β) super-family, and the insulin-like growth factor (IGF) family. In this chapter, in vivo actions of members of these growth factors described in the literature are compared with in vitro concepts of cartilage engineering making use of these growth factors.

Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

PubMed

Ververis, J; Ku, L; Delafontaine, P

1994-02-01

Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

PubMed

Lang, Charles H; Frost, Robert A

2002-05-01

The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

Involvement of {gamma}-secretase in postnatal angiogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayashi, Hiroki; Nakagami, Hironori; Takami, Yoichi

2007-11-23

{gamma}-Secretase cleaves the transmembrane domains of several integral membrane proteins involved in vasculogenesis. Here, we investigated the role of {gamma}-secretase in the regulation of postnatal angiogenesis using {gamma}-secretase inhibitors (GSI). In endothelial cell (EC), {gamma}-secretase activity was up-regulated under hypoxia or the treatment of vascular endothelial growth factor (VEGF). The treatment of GSI significantly attenuated growth factor-induced EC proliferation and migration as well as c-fos promoter activity in a dose-dependent manner. In vascular smooth muscle cell (VSMC), treatment of GSI significantly attenuated growth factor-induced VEGF and fibroblast growth factor-2 (FGF-2) expression. Indeed, GSI attenuated VEGF-induced tube formation and inhibited FGF-2-inducedmore » angiogenesis on matrigel in mice as quantified by FITC-lectin staining of EC. Overall, we demonstrated that {gamma}-secretase may be key molecule in postnatal angiogenesis which may be downstream molecule of growth factor-induced growth and migration in EC, and regulate the expression of angiogenic growth factors in VSMC.« less

Increased Serum Levels of Epidermal Growth Factor in Children with Autism

ERIC Educational Resources Information Center

Iseri, Elvan; Guney, Esra; Ceylan, Mehmet F.; Yucel, Aysegul; Aral, Arzu; Bodur, Sahin; Sener, Sahnur

2011-01-01

The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral…

Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report

PubMed Central

2011-01-01

Introduction Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. Case presentation We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. Conclusion The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained central hypothyroidism occurred during treatment. PMID:21745362

Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report.

PubMed

Cotta, Oana R; Santarpia, Libero; Curtò, Lorenzo; Aimaretti, Gianluca; Corneli, Ginevra; Trimarchi, Francesco; Cannavò, Salvatore

2011-07-11

Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained central hypothyroidism occurred during treatment.

Tissular growth factors profile after teduglutide administration on an animal model of intestinal anastomosis.

PubMed

Costa, Beatriz Pinto; Gonçalves, Ana Cristina; Abrantes, Ana Margarida; Alves, Raquel; Matafome, Paulo; Seiça, Raquel; Sarmento-Ribeiro, Ana Bela; Botelho, Maria Filomena; Castro-Sousa, Francisco

2018-01-16

Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis. Wistar rats (n = 59) were distributed into four groups: "ileal resection" or "laparotomy", each one subdivided into "postoperative teduglutide administration" or "no treatment"; and sacrificed at the third or the seventh day, with ileal sample harvesting. Gene expression of insulin-like growth factor 1 (Igf1), vascular endothelial growth factor a (Vegfa), transforming growth factor β1 (Tgfβ1), connective tissue growth factor (Ctgf), fibroblast growth factor 2 (Fgf2), fibroblast growth factor 7 (Fgf7), epidermal growth factor (Egf), heparin-binding epidermal-like growth factor (Hbegf), platelet-derived growth factor b (Pdgfb) and glucagon-like peptide 2 receptor (Glp2r)was studied by real-time polymerase chain reaction. Upregulation of Fgf7, Fgf2, Egf, Vegfaand Glp2rat the third day and of Pdgfat the seventh day was verified in the perianastomotic segment. Teduglutide administration was associated with higher fold-change of relative gene expression of Vegfa(3.6 ± 1.3 vs.1.9 ± 2.0, p = 0.0001), Hbegf(2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1(1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) and Ctgf(1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); and lower fold-change of Tgfβ1, Fgf7and Glp2r. Those results underscore the recognized role of Igf1and Hbegfas molecular mediators of the effects of teduglutide and suggest that other humoral factors, like Vegfand Ctgf, may also be relevant in the perioperative context. Induction of Vegfa, Igf1and Ctgfgene expressions might indicate a favorable influence of teduglutide on the intestinal anastomotic healing.

Receptor control in mesenchymal stem cell engineering

NASA Astrophysics Data System (ADS)

Dalby, Matthew J.; García, Andrés J.; Salmeron-Sanchez, Manuel

2018-03-01

Materials science offers a powerful tool to control mesenchymal stem cell (MSC) growth and differentiation into functional phenotypes. A complex interplay between the extracellular matrix and growth factors guides MSC phenotypes in vivo. In this Review, we discuss materials-based bioengineering approaches to direct MSC fate in vitro and in vivo, mimicking cell-matrix-growth factor crosstalk. We first scrutinize MSC-matrix interactions and how the properties of a material can be tailored to support MSC growth and differentiation in vitro, with an emphasis on MSC self-renewal mechanisms. We then highlight important growth factor signalling pathways and investigate various materials-based strategies for growth factor presentation and delivery. Integrin-growth factor crosstalk in the context of MSC engineering is introduced, and bioinspired material designs with the potential to control the MSC niche phenotype are considered. Finally, we summarize important milestones on the road to MSC engineering for regenerative medicine.

Circulating growth factors data associated with insulin secretagogue use in women with incident breast cancer.

PubMed

Wintrob, Zachary A P; Hammel, Jeffrey P; Nimako, George K; Gaile, Dan P; Forrest, Alan; Ceacareanu, Alice C

2017-04-01

Oral drugs stimulating insulin production may impact growth factor levels. The data presented shows the relationship between pre-existing insulin secretagogues use, growth factor profiles at the time of breast cancer diagnosis and subsequent cancer outcomes in women diagnosed with breast cancer and type 2 diabetes mellitus. A Pearson correlation analysis evaluating the relationship between growth factors stratified by diabetes pharmacotherapy and controls is also provided.

Role of Autophagy in Keratin Homeostasis in Breast Cancer

DTIC Science & Technology

2012-12-01

commences where the mammary gland reverts to its pre- pregnant state (Brisken and O’Malley, 2010). Pubertal mouse mammary gland development, which...prolactin and local growth factors such as Insulin growth factor-1 (IGF-1), Hepatocyte growth factor (HGF), and Fibroblast growth factor (FGF) (Parmar...iMMECs   overexpressing  Bcl-­‐2  by  lentiviral  infection.    Following  infection,   resistant  colonies   were

Angiogenic factors in chronic lymphocytic leukaemia (CLL): Where do we stand?

PubMed

Aguirre Palma, Luis Mario; Gehrke, Iris; Kreuzer, Karl-Anton

2015-03-01

The role of angiogenesis in haematological malignancies such as chronic lymphocytic leukaemia (CLL) is difficult to envision, because leukaemia cells are not dependent on a network of blood vessels to support basic physiological requirements. Regardless, CLL cells secrete high levels of major angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF). Nonetheless, it remains unclear how most angiogenic factors regulate accumulation and delayed apoptosis of CLL cells. Angiogenic factors such as leptin, granulocyte colony-stimulating factor (G-CSF), follistatin, angiopoietin-1 (Ang1), angiogenin (ANG), midkine (MK), pleiotrophin (PTN), progranulin (PGRN), proliferin (PLF), placental growth factor (PIGF), and endothelial locus-1 (Del-1), represent novel therapeutic targets of future CLL research but have remained widely overlooked. This review aims to outline our current understanding of angiogenic growth factors and their relationship with CLL, a still uncured haematopoietic malignancy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

PubMed Central

Moises, Hans W; Zoega, Tomas; Gottesman, Irving I

2002-01-01

Background A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. Presentation of the hypothesis Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. Testing the hypothesis Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. Implications of the hypothesis The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments. PMID:12095426

Localisation of stem cell factor, stanniocalcin-1, connective tissue growth factor and heparin-binding epidermal growth factor in the bovine uterus at the time of blastocyst formation.

PubMed

Muñoz, M; Martin, D; Carrocera, S; Alonso-Guervos, M; Mora, M I; Corrales, F J; Peynot, N; Giraud-Delville, C; Duranthon, V; Sandra, O; Gómez, E

2017-10-01

Early embryonic losses before implantation account for the highest rates of reproductive failure in mammals, in particular when in vitro-produced embryos are transferred. In the present study, we used molecular biology techniques (real-time quantitative polymerase chain reaction), classical immunohistochemical staining coupled with confocal microscopy and proteomic analysis (multiple reaction monitoring and western blot analysis) to investigate the role of four growth factors in embryo-uterine interactions during blastocyst development. Supported by a validated embryo transfer model, the study investigated: (1) the expression of stem cell factor (SCF), stanniocalcin-1 (STC1), connective tissue growth factor (CTGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) in bovine uterine fluid; (2) the presence of SCF, STC1, CTGF and HB-EGF mRNA and protein in the bovine endometrium and embryos; and (3) the existence of reciprocal regulation between endometrial and embryonic expression of SCF, STC1, CTGF and HB-EGF. The results suggest that these growth factors most likely play an important role during preimplantation embryo development in cattle. The information obtained from the present study can contribute to improving the performance of in vitro culture technology in cattle and other species.

A cytokine axis regulates elastin formation and degradation

PubMed Central

Sproul, Erin P.; Argraves, W. Scott

2013-01-01

Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine–governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin–cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production. PMID:23160093

Theileria parva infection induces autocrine growth of bovine lymphocytes.

PubMed Central

Dobbelaere, D A; Coquerelle, T M; Roditi, I J; Eichhorn, M; Williams, R O

1988-01-01

Bovine lymphocytes infected with the parasite Theileria parva continuously secrete a growth factor that is essential for their proliferation in vitro and also constitutively express interleukin 2 receptors on their surface. Dilution of the secreted growth factor, caused by culturing cells at low density, results in retardation of culture growth. Human recombinant interleukin 2, however, effectively substitutes for the diluted growth factor by restoring normal growth rates and also allows Theileria-infected cells to be grown at low density without the use of feeder layers. Secretion of the growth factor and expression of the interleukin 2 receptor depend on the presence of the parasite in the cytoplasm of the host cell. Elimination of the parasite from the cell cytoplasm by the specific antitheilerial drug BW 720c results in the arrest of growth factor secretion and the disappearance of interleukin 2 receptors from the cell surface. This is accompanied by growth arrest and reversion of the infected cells to the morphology of resting lymphocytes. We propose that the continuous proliferation of infected cells in vitro is mediated by autocrine receptor activation. Images PMID:3133661

Regulation of Transforming Growth Factor β1, Platelet-Derived Growth Factor, and Basic Fibroblast Growth Factor by Silicone Gel Sheeting in Early-Stage Scarring.

PubMed

Choi, Jaehoon; Lee, Eun Hee; Park, Sang Woo; Chang, Hak

2015-01-01

Hypertrophic scars and keloids are associated with abnormal levels of growth factors. Silicone gel sheets are effective in treating and preventing hypertrophic scars and keloids. There has been no report on the change in growth factors in the scar tissue following the use of silicone gel sheeting for scar prevention. A prospective controlled trial was performed to evaluate whether growth factors are altered by the application of a silicone gel sheet on a fresh surgical scar. Four of seven enrolled patients completed the study. Transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) were investigated immunohistochemically in biopsies taken from five scars at 4 months following surgery. In both the epidermis and the dermis, the expression of TGF-β1 (P=0.042 and P=0.042) and PDGF (P=0.043 and P=0.042) was significantly lower in the case of silicone gel sheet-treated scars than in the case of untreated scars. The expression of bFGF in the dermis was significantly higher in the case of silicone gel sheet-treated scars than in the case of untreated scars (P=0.042), but in the epidermis, the expression of bFGF showed no significant difference between the groups (P=0.655). The levels of TGF-β1, PDGF, and bFGF are altered by the silicone gel sheet treatment, which might be one of the mechanisms of action in scar prevention.

Balance of antiangiogenic and angiogenic factors in the context of the etiology of preeclampsia.

PubMed

Seki, Hiroyuki

2014-10-01

The "two-stage disorder" theory that is assumed for the etiology of preeclampsia hypothesizes that antiangiogenic and angiogenic factors and/or placental debris play an important role in this disorder. The physiological actions of placental debris occur via the balance between antiangiogenic and angiogenic factors. Accordingly, this balance between antiangiogenic and angiogenic factors should be investigated to elucidate the various pathological features of preeclampsia. Their accurate evaluation is needed to investigate not only antiangiogenic factors (such as sFlt-1 and sEng) and angiogenic factors (such as vascular endothelial growth factor, placental growth factor and transforming growth factor-β) but also the expression level of their receptors such as Flt-1 and Eng. However, it is ethically and technically difficult to investigate the above-mentioned factors at antepartum in human patients. The examination of the ratios of sFlt-1/vascular endothelial growth factor receptor ligands and sEng/transforming vascular endothelial growth factor-β and the use of experimental animal models may help in elucidating various unresolved issues in preeclampsia. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

PubMed

Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

2017-02-01

Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p < 0.001) and RAB11FIP3 ( r = 0.165, p = 0.005) expression. The multivariate Cox proportional hazard model analysis demonstrated that the expression of Eps15 homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.

A highly versatile adaptor protein for the tethering of growth factors to gelatin-based biomaterials.

PubMed

Addi, Cyril; Murschel, Frédéric; Liberelle, Benoît; Riahi, Nesrine; De Crescenzo, Gregory

2017-03-01

In the field of tissue engineering, the tethering of growth factors to tissue scaffolds in an oriented manner can enhance their activity and increase their half-life. We chose to investigate the capture of the basic Fibroblast Growth Factor (bFGF) and the Epidermal Growth Factor (EGF) on a gelatin layer, as a model for the functionalization of collagen-based biomaterials. Our strategy relies on the use of two high affinity interactions, that is, the one between two distinct coil peptides as well as the one occurring between a collagen-binding domain (CBD) and gelatin. We expressed a chimeric protein to be used as an adaptor that comprises one of the coil peptides and a CBD derived from the human fibronectin. We proved that it has the ability to bind simultaneously to a gelatin substrate and to form a heterodimeric coiled-coil domain with recombinant growth factors being tagged with the complementary coil peptide. The tethering of the growth factors was characterized by ELISA and surface plasmon resonance-based biosensing. The bioactivity of the immobilized bFGF and EGF was evaluated by a human umbilical vein endothelial cell proliferation assay and a vascular smooth muscle cell survival assay. We found that the tethering of EGF preserved its mitogenic and anti-apoptotic activity. In the case of bFGF, when captured via our adaptor protein, changes in its natural mode of interaction with gelatin were observed. In an effort to functionalize collagen/gelatin-based biomaterials with growth factors, we have designed an adaptor protein corresponding to a collagen-binding domain fused to a coil peptide. In our strategy, this adaptor protein captures growth factors being tagged with the partner coil peptide in a specific, stable and oriented manner. We have found that the tethering of the Epidermal Growth Factor preserved its mitogenic and anti-apoptotic activity. In the case of the basic Fibroblast Growth Factor, the captured growth factor remained bioactive although its tethering via this adaptor protein modified its natural mode of interaction with gelatin. Altogether this strategy is easily adaptable to the simultaneous tethering of various growth factors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

PubMed

Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

2015-10-01

Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without BM invasion showing high level of bone marrow plasma vascular endothelial growth factor per platelet count had significantly shorter progression-free survival and overall survival. Bone marrow plasma vascular endothelial growth factor level per platelet count might be associated with bone marrow invasion by diffuse large B-cell lymphoma and is correlated with clinical outcomes after treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Osteotome-Mediated Sinus Lift without Grafting Material: A Review of Literature and a Technique Proposal

PubMed Central

Taschieri, Silvio; Corbella, Stefano; Saita, Massimo; Tsesis, Igor; Del Fabbro, Massimo

2012-01-01

Implant rehabilitation of the edentulous posterior maxilla may be a challenging procedure in the presence of insufficient bone volume for implant placement. Maxillary sinus augmentation with or without using grafting materials aims to provide adequate bone volume. The aim of the present study was to systematically review the existing literature on transalveolar maxillary sinus augmentation without grafting materials and to propose and describe an osteotome-mediated approach in postextraction sites in combination with platelet derivative. The systematic review showed that high implant survival rate (more than 96% after 5 years) can be achieved even without grafting the site, with a low rate of complications. Available alveolar bone height before surgery was not correlated to survival rate. In the described case report, three implants were placed in posterior maxilla after extraction of two teeth. An osteotome-mediated sinus lifting technique was performed with the use of platelet derivative (PRGF); a synthetic bone substitute was used to fill the gaps between implant and socket walls. No complications occurred, and implants were successfully in site after 1 year from prosthetic loading. The presented technique might represent a viable alternative for the treatment of edentulous posterior maxilla with atrophy of the alveolar bone though it needs to be validated by studies with a large sample size. PMID:22792108

Effect of houttuynia cordata aetherolea on adiponectin and connective tissue growth factor in a rat model of diabetes mellitus.

PubMed

Wang, Hai-Ying; Bao, Jun-Lu

2012-03-01

To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus (DM). DM was induced in rats using streptozotocin (STZ) and high glucose-lipid animal feed. Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks. Changes in connective tissue growth factor and adiponectin levels in rats were observed. Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment. Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

PubMed Central

Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

2018-01-01

Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells.

PubMed

Choi, Nahyun; Shin, Soyoung; Song, Sun U; Sung, Jong-Hyuk

2018-02-28

Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

Insulin-Like Growth Factor and Epidermal Growth Factor Signaling in Breast Cancer Cell Growth: Focus on Endocrine Resistant Disease

PubMed Central

Berdiaki, Aikaterini; Tzardi, Maria

2015-01-01

Breast cancer is the most common type of cancer for women worldwide with a lifetime risk amounting to a staggering total of 10%. It is well established that the endogenous synthesis of insulin-like growth factor (IGF) and epidermal growth factor (EGF) polypeptide growth factors are closely correlated to malignant transformation and all the steps of the breast cancer metastatic cascade. Numerous studies have demonstrated that both estrogens and growth factors stimulate the proliferation of steroid-dependent tumor cells, and that the interaction between these signaling pathways occurs at several levels. Importantly, the majority of breast cancer cases are estrogen receptor- (ER-) positive which have a more favorable prognosis and pattern of recurrence with endocrine therapy being the backbone of treatment. Unfortunately, the majority of patients progress to endocrine therapy resistant disease (acquired resistance) whereas a proportion of patients may fail to respond to initial therapy (de novo resistance). The IGF-I and EGF downstream signaling pathways are closely involved in the process of progression to therapy resistant disease. Modifications in the bioavailability of these growth factors contribute critically to disease progression. In the present review therefore, we will discuss in depth how IGF and EGF signaling participate in breast cancer pathogenesis and progression to endocrine resistant disease. PMID:26258011

No causal impact of serum vascular endothelial growth factor level on temporal changes in body mass index in Japanese male workers: a five-year longitudinal study.

PubMed

Imatoh, Takuya; Kamimura, Seiichiro; Miyazaki, Motonobu

2017-03-01

It has been reported that adipocytes secrete vascular endothelial growth factor. Therefore, we conducted a 5-year longitudinal epidemiological study to further elucidate the association between vascular endothelial growth factor levels and temporal changes in body mass index. Our study subjects were Japanese male workers, who had regular health check-ups. Vascular endothelial growth factor levels were measured at baseline. To examine the association between vascular endothelial growth factor levels and overweight, we calculated the odds ratio using a multivariate logistic regression model. Moreover, linear mixed effect models were used to assess the association between vascular endothelial growth factor level and temporal changes in body mass index during the 5-year follow-up period. Vascular endothelial growth factor levels were marginally higher in subjects with a body mass index greater than 25 kg/m 2 compared with in those with a body mass index less than 25 kg/m 2 (505.4 vs. 465.5 pg/mL, P = 0.1) and were weakly correlated with leptin levels (β: 0.05, P = 0.07). In multivariate logistic regression, subjects in the highest vascular endothelial growth factor quantile were significantly associated with an increased risk for overweight compared with those in the lowest quantile (odds ratio 1.65, 95 % confidential interval: 1.10-2.50). Moreover P for trend was significant (P for trend = 0.003). However, the linear mixed effect model revealed that vascular endothelial growth factor levels were not associated with changes in body mass index over a 5-year period (quantile 2, β: 0.06, P = 0.46; quantile 3, β: -0.06, P = 0.45; quantile 4, β: -0.10, P = 0.22; quantile 1 as reference). Our results suggested that high vascular endothelial growth factor levels were significantly associated with overweight in Japanese males but high vascular endothelial growth factor levels did not necessarily cause obesity.

[Effect of cryotherapy over the expression of vascular endothelial growth factor and pigment epithelium-derived factor].

PubMed

Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier

2014-01-01

Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

Low fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women

USDA-ARS?s Scientific Manuscript database

The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, the nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in normal individuals are not well-defined. The purpose of this study was to determine the ...

Modeling invasive breast cancer: growth factors propel progression of HER2-positive premalignant lesions

PubMed Central

Pradeep, C-R; Zeisel, A; Köstler, WJ; Lauriola, M; Jacob-Hirsch, J; Haibe-Kains, B; Amariglio, N; Ben-Chetrit, N; Emde, A; Solomonov, I; Neufeld, G; Piccart, M; Sagi, I; Sotiriou, C; Rechavi, G; Domany, E; Desmedt, C; Yarden, Y

2013-01-01

The HER2/neu oncogene encodes a receptor-like tyrosine kinase whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. However, the mechanisms underlying aggressiveness of HER2 (human epidermal growth factor receptor 2)-overexpressing tumors remain incompletely understood. Because it assists epidermal growth factor (EGF) and neuregulin receptors, we overexpressed HER2 in MCF10A mammary cells and applied growth factors. HER2-overexpressing cells grown in extracellular matrix formed filled spheroids, which protruded outgrowths upon growth factor stimulation. Our transcriptome analyses imply a two-hit model for invasive growth: HER2-induced proliferation and evasion from anoikis generate filled structures, which are morphologically and transcriptionally analogous to preinvasive patients’ lesions. In the second hit, EGF escalates signaling and transcriptional responses leading to invasive growth. Consistent with clinical relevance, a gene expression signature based on the HER2/EGF-activated transcriptional program can predict poorer prognosis of a subgroup of HER2-overexpressing patients. In conclusion, the integration of a three-dimensional cellular model and clinical data attributes progression of HER2-overexpressing lesions to EGF-like growth factors acting in the context of the tumor's microenvironment. PMID:22139081

The effects of oxcarbazepine and valproate therapies on growth in children with epilepsy.

PubMed

Cansu, Ali; Yesilkaya, Ediz; Serdaroglu, Ayse; Camurdan, Orhun; Hirfanoglu, Tugba Luleci; Karaoglu, Abdulbaki; Bideci, Aysun; Cinaz, Peyami

2012-01-01

This study aimed to evaluate the effects of monotherapy with valproate or oxcarbazepine on the linear growth of children with idiopathic epilepsy. Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76 patients. These were evaluated at baseline and at 6 and 18 months after commencement of therapy to determine height standard deviations (height z-scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 levels were measured. In prepubertal patients receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a significant increase was noted at the 18th month of therapy (p = 0.004). In prepubertal patients receiving oxcarbazepine, serum standardized insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels were significantly higher at the 18th month of therapy compared with baseline (p = 0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate, serum ghrelin levels were significantly decreased at the 18th month of therapy compared with baseline (p = 0.006). Exposure to oxcarbazepine stimulated linear growth in epileptic patients through mechanisms involving the release of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. In contrast, expo-sure to valproate did not affect linear growth, but did lead to a decrease in serum ghrelin levels.

Comparison of fibrin clots derived from peripheral blood and bone marrow.

PubMed

Shoji, Takeshi; Nakasa, Tomoyuki; Yoshizuka, Masaaki; Yamasaki, Takuma; Yasunaga, Yuji; Adachi, Nobuo; Ochi, Mitsuo

2017-03-01

Autologous fibrin clots derived from peripheral blood (pb-fibrin clot) and bone marrow (bm-fibrin clot) are thought to be effective for tissue regeneration. However, there is no report detailing the amount of growth factors in pb-/bm-fibrin clot. In this study we evaluated the amount of growth factors in human pb-/bm-fibrin clot, and prove the validity of fibrin clot for clinical use. Human pb-/bm-fibrin clots were obtained during surgery. In the first experiment, enzyme-linked immunosorbent assay (ELISA) was performed for detecting the amount of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor basic (bFGF), hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-β), platelet derived-growth factors-AB (PDGF-AB), and stromal cell-derived factor-1 (SDF-1). In the second experiment, the efficacy of fibrin clot on the osteogenic differentiation and fibroblast proliferation was evaluated. Pb-/bm-fibrin clots were incubated in human osteoblast derived from mesenchymal stromal cells (MSCs) or human skin fibroblast. Alizarin red staining and real-time PCR (COL1A1, RUNX2) were performed for the detection of osteogenic potential. Cell-growth assay (WST-8) and real-time PCR (COL1A1) were also performed for the detection of the potential of fibroblast proliferation. ELISA analysis revealed that the amount of VEGF, HGF, bFGF, IGF-1, and SDF-1 of bm-fibrin clot group is higher than that of pb-fibrin clot group with statistical differences. Besides, we confirmed that bm-fibrin clot has much potential for the osteogenic differentiation and fibroblast proliferation. The positive outcomes confirm the efficacy of pb-/bm-fibrin clot, and bm-fibrin clot was proved to have much potential for tissue regeneration compared with pb-fibrin clot. The current study showed the potential of a strategy for regenerative medicine using bm-fibrin clot.

Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level

PubMed Central

Chen, Jan-Yow; Liu, Jiung-Hsiun; Wu, Hong-Dar Isaac; Lin, Kuo-Hung; Chang, Kuan-Cheng; Liou, Ying-Ming

2016-01-01

Background Familial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome. Methods Overall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1. Results Two transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16–3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls. Conclusion Transforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome. PMID:27380173

Quantification of platelets and platelet derived growth factors from platelet-rich-plasma (PRP) prepared at different centrifugal force (g) and time.

PubMed

Arora, Satyam; Doda, Veena; Kotwal, Urvershi; Dogra, Mitu

2016-02-01

Platelet derived biomaterials represent a key source of cytokines and growth factors extensively used for tissue regeneration; wound healing and tissue repair. Our study was to quantify platelets and growth factors released by PRP when prepared at different centrifugal force (g) and time. Our study was approved by the institutional ethical committee. One hundred millilitres of whole blood (WB) was collected in bag with CPDA as the anticoagulant(AC); (14 mL for 100 mL WB ratio). Nine aliquots of 10 mL each were made from the bag and set of three aliquots were made a group. PRP was prepared at varying centrifugal force (group A: -110 g, group B: -208 g & group C: -440 g) & time (1: -5 min, 2: -10 min & 3: -20 min). Contents of each PRP prepared were analysed. Commercial sandwich ELISA kits were used to quantify the concentrations of CD62P (Diaclone SAS; France), Platelet derived growth factors-AB (Qayee-Bio; China), transforming growth factor-β1 (DRG; Germany) and vascular endothelial growth factor (Boster Immuno Leader; USA) released in each PRP prepared. Eight volunteers were enrolled in the study (24-30 years). The baseline blood counts of all the volunteers were comparable (p ≥ 0.05). Mean ± SD of platelet yield of all nine groups ranged from 17.2 ± 4.2% to 78.7 ± 5.7%. Each PRP was activated with calcified thromboplastin to quantify the growth factors released by them. Significantly higher (p < 0.05) transforming growth factor-β1 and vascular endothelial growth factor were released compared to the baseline. Our study highlights the variation in both force (g) and time results in changes at cellular level and growth factor concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Constructing a blood vessel on the porous scaffold modified with vascular endothelial growth factor and basic fibroblast growth factor

NASA Astrophysics Data System (ADS)

Sevostyanova, V. V.; Matveeva, V. G.; Antonova, L. V.; Velikanova, E. A.; Shabaev, A. R.; Senokosova, E. A.; Krivkina, E. O.; Vasyukov, G. Yu.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S.

2016-11-01

Incorporation of the growth factors into biodegradable polymers is a promising approach for the fabrication of tissue-engineered vascular grafts. Here we blended poly(ɛ-caprolactone) (PCL) with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) following incorporation of either vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) and then fabricated electrospun 2 mm diameter vascular grafts. Grafts without the growth factors were used as a control group. Structure of the grafts was assessed utilizing scanning electron microscopy. We further implanted our grafts into rat abdominal aorta for 1 and 3 months with the aim to test endothelialization, cell infiltration, and patency in vivo. Histological and immunofluorescence examination demonstrated enhanced endothelialization and cell infiltration of the grafts with either VEGF or bFGF compared to those without the growth factors. Grafts with VEGF showed higher patency compared to those with bFGF; however, bFGF promoted migration of smooth muscle cells and fibroblasts into the graft. Therefore, we conclude that incorporation of VEGF and bFGF into the inner and medial/outer layer, respectively, can be a promising option for the fabrication of tissue-engineered vascular grafts.

[Pathogenetic and Prognostic Role of Growth Factors in the Development of Chronic Heart Failure].

PubMed

Teplyakov, A T; Berezikova, E N; Shilov, S N; Efremova, A V; Pustovetova, M G; Popova, A A; Grakova, E V; Torim, Y Y; Safronov, I D; Andriyanova, A V

2017-10-01

To study the role of growth factors ((vascular endothelial growth factor (VEGF), platelet derived growth factor AB (PDGF-AB) and basic fibroblast growth factor (FGF-basic)) in the development and progression of chronic heart failure (CHF) in patients with ishcemic heart disease (IHD). We included in this study 94 patients with CHF. The control group comprised 32 persons. Blood serum levels of growth factors were determined at baseline and after 12 months of observation by enzyme-linked immunosorbent assay. VEGF, PDGF-AB and FGF-basic play an important role in the pathogenesis and progression of heart failure in patients with IHD, determining the increased risk of adverse cardiovascular events in this pathology. Serum activity of growth factors characterizes the severity and course of CHF: with disease progression levels of VEGF and FGF-basic decrease and PDGF-AB concentration increases. Initial low level of VEGF expression regardless of the sex of the patient's sex, significantly low level of FGF-basic and significantly high PDGF-AB in men characterizes unfavorable course of CHF. A correlation has been established between blood serum levels of VEGF, PDGF-AB and FGF-basic and severity and course of CHF.

[Therapeutic use of hematopoietic growth factors. II. GM-CSF and G-CSF].

PubMed

Royer, B; Arock, M

1998-01-01

The second part of this review on haematopoietic growth factors is focused on the therapeutic use of GM-CSF and G-CSF. Such therapeutic applications have raised very great hopes for clinical haematology. However, it should not be forgotten that these haematopoietic growth factors, which are very costly, are powerful two-edged weapons capable of triggering a cascade of reactions, and have a field of activity that often goes beyond the single highly specific property which it is hoped they possess. The risks and costs of their use are currently being evaluated. Waited developments concerning these molecules focus on three axes: a best use of factors already commercialized, especially concerning adaptation of posologies and new indications, the development of hybrid molecules from already known haematopoietic growth factors, possessing the advantages of respective factors, but not their disadvantages, the discovery of new haematopoietic growth factors with potential therapeutic application.

Role of Gab1 in Heart, Placenta, and Skin Development and Growth Factor- and Cytokine-Induced Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Activation

PubMed Central

Itoh, Motoyuki; Yoshida, Yuichi; Nishida, Keigo; Narimatsu, Masahiro; Hibi, Masahiko; Hirano, Toshio

2000-01-01

Gab1 is a member of the Gab/DOS (Daughter of Sevenless) family of adapter molecules, which contain a pleckstrin homology (PH) domain and potential binding sites for SH2 and SH3 domains. Gab1 is tyrosine phosphorylated upon stimulation of various cytokines, growth factors, and antigen receptors in cell lines and interacts with signaling molecules, such as SHP-2 and phosphatidylinositol 3-kinase, although its biological roles have not yet been established. To reveal the functions of Gab1 in vivo, we generated mice lacking Gab1 by gene targeting. Gab1-deficient embryos died in utero and displayed developmental defects in the heart, placenta, and skin, which were similar to phenotypes observed in mice lacking signals of the hepatocyte growth factor/scatter factor, platelet-derived growth factor, and epidermal growth factor pathways. Consistent with these observations, extracellular signal-regulated kinase mitogen-activated protein (ERK MAP) kinases were activated at much lower levels in cells from Gab1-deficient embryos in response to these growth factors or to stimulation of the cytokine receptor gp130. These results indicate that Gab1 is a common player in a broad range of growth factor and cytokine signaling pathways linking ERK MAP kinase activation. PMID:10779359

Localized delivery of growth factors for periodontal tissue regeneration: role, strategies, and perspectives.

PubMed

Chen, Fa-Ming; Shelton, Richard M; Jin, Yan; Chapple, Iain L C

2009-05-01

Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self-regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus.

Autocrine and/or paracrine insulin-like growth factor-I activity in skeletal muscle

NASA Technical Reports Server (NTRS)

Adams, Gregory R.

2002-01-01

Similar to bone, skeletal muscle responds and adapts to changes in loading state via mechanisms that appear to be intrinsic to the muscle. One of the mechanisms modulating skeletal muscle adaptation it thought to involve the autocrine and/or paracrine production of insulinlike growth factor-I. This brief review outlines components of the insulinlike growth factor-I system as it relates to skeletal muscle and provides the rationale for the theory that insulinlike growth factor-I is involved with muscle adaptation.

Dataset on growth factor levels and insulin use in patients with diabetes mellitus and incident breast cancer.

PubMed

Wintrob, Zachary A P; Hammel, Jeffrey P; Nimako, George K; Gaile, Dan P; Forrest, Alan; Ceacareanu, Alice C

2017-04-01

Growth factor profiles could be influenced by the utilization of exogenous insulin. The data presented shows the relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, the growth factor profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between growth factors stratified by of insulin use and controls is also provided.

Intestinal hormones and growth factors: Effects on the small intestine

PubMed Central

Drozdowski, Laurie; Thomson, Alan BR

2009-01-01

There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In partI, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part II will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids. PMID:19152442

Novel Growth Factor as Prognostic Marker for Estrogen-Independence in Breast Cancer

DTIC Science & Technology

2002-08-01

factor (PCDGF, also known as progranulin ) is a novel autocrine growth factor shown to be overexpressed and to be mitogenic in human breast cancer cell...kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC (1, 2). PCDGF (also known as progranulin ) is the...requirement for the insulin-like growth factor 1 receptor for growth in vitro. J Biol Chem, 273: 20078-20083, 1998. 6. He, Z. and Bateman, A. Progranulin gene

The Effects of Autocorrelation on the Curve-of-Factors Growth Model

ERIC Educational Resources Information Center

Murphy, Daniel L.; Beretvas, S. Natasha; Pituch, Keenan A.

2011-01-01

This simulation study examined the performance of the curve-of-factors model (COFM) when autocorrelation and growth processes were present in the first-level factor structure. In addition to the standard curve-of factors growth model, 2 new models were examined: one COFM that included a first-order autoregressive autocorrelation parameter, and a…

Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

PubMed

Bortvedt, Sarah F; Lund, P Kay

2012-03-01

To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

Assessment of insulin-like growth factor-1 (IGF-I) level in patients with rheumatic mitral stenosis.

PubMed

Deveci, Onur S; Yavuz, Bunyamin; Sen, Omer; Deniz, Ali; Ozkan, Selcuk; Dal, Kursat; Ata, Naim; Baser, Salih; Akin, Kadir O; Kucukazman, Metin; Beyan, Esin; Ertugrul, Derun T

2015-03-01

Insulin-like growth factor-1 may serve some regulatory function in the immune system. Rheumatic mitral stenosis is related to autoimmune heart valve damage after streptococcal infection. The aim of this study was to assess the level of insulin-like growth factor-1 and its correlation with the Wilkins score in patients with rheumatic mitral stenosis. A total of 65 patients with rheumatic mitral stenosis and 62 age- and sex-matched control subjects were enrolled in this study. All subjects underwent transthoracic echocardiography. The mitral valve area and Wilkins score were evaluated for all patients. Biochemical parameters and serum insulin-like growth factor-1 levels were measured. Demographic data were similar in the rheumatic mitral stenosis and control groups. The mean mitral valve area was 1.6±0.4 cm2 in the rheumatic mitral stenosis group. The level of insulin-like growth factor-1 was significantly higher in the rheumatic mitral stenosis group than in the control group (104 (55.6-267) versus 79.1 (23.0-244.0) ng/ml; p=0.039). There was a significant moderate positive correlation between insulin-like growth factor-1 and thickening of leaflets score of Wilkins (r=0.541, p<0.001). The present study demonstrated that serum insulin-like growth factor-1 levels were significantly higher in the rheumatic mitral stenosis group compared with control subjects and that insulin-like growth factor-1 level was also correlated with the Wilkins score. It can be suggested that there may be a link between insulin-like growth factor-1 level and immune pathogenesis of rheumatic mitral stenosis.

rhEGF-containing thermosensitive and mucoadhesive polymeric sol-gel for endoscopic treatment of gastric ulcer and bleeding.

PubMed

Maeng, Jin Hee; So, Jung Won; Kim, Jungju; Kim, In Ae; Jung, Ji Hoon; Min, Kyunghyun; Lee, Don Haeng; Yang, Su-Geun

2014-03-01

Gastrointestinal endoscopy is a standard diagnostic tool for gastrointestinal ulcers and cancer. In this study, we have developed recombinant human epidermal growth factor-containing ulcer-coating polymeric sol-gel for endoscopic application. Chitosan and pluronic F127 were employed for their thermoresponsive and bioadhesive properties. At temperatures below 21, polymeric sol-gel remains liquid during endoscopic application and transforms to gel at body temperature after application on ulcers. In an in vitro cellular wounding assay, recombinant human epidermal growth factor sol-gel significantly enhanced the cell migration and decreased the wounding area (68%) compared to nontreated, recombinant human epidermal growth factor solution, and sol-gel without recombinant human epidermal growth factor (42, 49, and 32 % decreased at day 1). The in vivo ulcer-healing study was performed in an acetic acid-induced gastric ulcer rat model and proved that our recombinant human epidermal growth factor endoscopic sol-gel facilitated the ulcer-healing process more efficiently than the other treatments. Ulcer sizes in the recombinant human epidermal growth factor sol-gel group were decreased 2.9- and 2.1-fold compared with those in the nontreated group on days 1 and 3 after ulceration, respectively. The mucosal thickness in the recombinant human epidermal growth factor sol-gel group was significantly increased compared to that in the nontreated group (3.2- and 6.9-fold on days 1 and 3 after ulceration, respectively). In a gastric retention study, recombinant human epidermal growth factor sol-gel stayed on the gastric mucosa more than 2 h after application. The present study suggests that recombinant human epidermal growth factor sol-gel is a prospective candidate for treating gastric ulcers via endoscopic application.

Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa.

PubMed

Hasegawa, Mayumi; Cheng, Jun; Maruyama, Satoshi; Yamazaki, Manabu; Abé, Tatsuya; Babkair, Hamzah; Saito, Chikara; Saku, Takashi

2016-05-01

The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Interactions of cytokines, growth factors, and the extracellular matrix in the cellular biology of uterine leiomyomata.

PubMed

Sozen, Ibrahim; Arici, Aydin

2002-07-01

To review the available information regarding the role of cytokines, growth factors, and the extracellular matrix in the pathophysiology of uterine leiomyomata and to integrate this information in a suggested model of disease at the cellular level. A thorough literature and MEDLINE search was conducted to identify the relevant studies in the English literature published between January, 1966 and October, 2001. A model of disease at the cellular level was developed using the most likely cytokines to be involved in the pathogenesis of leiomyomata as determined by our assessment of the available literature. A number of cytokines and growth factors, including transforming growth factor-beta (TGF-beta), epidermal growth factor, monocyte chemotactic protein-1, insulin-like growth factors 1 and 2, prolactin, parathyroid-hormone-related peptide, basic fibroblast growth factor, platelet-derived growth factor, interleukin-8, and endothelin, have been investigated in myometrium and leiomyoma. Among these cytokines, TGF-beta appears to be the only growth factor that has been shown to be overexpressed in leiomyoma vs. myometrium, be hormonally-regulated both in vivo and in vitro, and be both mitogenic and fibrogenic in these tissues. In addition to the cytokines, extracellular matrix components such as collagen, fibronectin, proteoglycans, matrix metalloproteinases, and tissue inhibitors of metalloproteinases seem to play pivotal roles in the pathogenesis of leiomyomata. We believe that, given the extent and depth of the current research on the cellular biology of leiomyomata, the cellular mechanisms responsible in the pathogenesis of leiomyomata will be identified clearly within the foreseeable future. This will enable researchers to develop therapy directed against the molecules and mechanisms at the cellular level.

Comparison of point-of-care methods for preparation of platelet concentrate (platelet-rich plasma).

PubMed

Weibrich, Gernot; Kleis, Wilfried K G; Streckbein, Philipp; Moergel, Maximilian; Hitzler, Walter E; Hafner, Gerd

2012-01-01

This study analyzed the concentrations of platelets and growth factors in platelet-rich plasma (PRP), which are likely to depend on the method used for its production. The cellular composition and growth factor content of platelet concentrates (platelet-rich plasma) produced by six different procedures were quantitatively analyzed and compared. Platelet and leukocyte counts were determined on an automatic cell counter, and analysis of growth factors was performed using enzyme-linked immunosorbent assay. The principal differences between the analyzed PRP production methods (blood bank method of intermittent flow centrifuge system/platelet apheresis and by the five point-of-care methods) and the resulting platelet concentrates were evaluated with regard to resulting platelet, leukocyte, and growth factor levels. The platelet counts in both whole blood and PRP were generally higher in women than in men; no differences were observed with regard to age. Statistical analysis of platelet-derived growth factor AB (PDGF-AB) and transforming growth factor β1 (TGF-β1) showed no differences with regard to age or gender. Platelet counts and TGF-β1 concentration correlated closely, as did platelet counts and PDGF-AB levels. There were only rare correlations between leukocyte counts and PDGF-AB levels, but comparison of leukocyte counts and PDGF-AB levels demonstrated certain parallel tendencies. TGF-β1 levels derive in substantial part from platelets and emphasize the role of leukocytes, in addition to that of platelets, as a source of growth factors in PRP. All methods of producing PRP showed high variability in platelet counts and growth factor levels. The highest growth factor levels were found in the PRP prepared using the Platelet Concentrate Collection System manufactured by Biomet 3i.

Sequential growth factor application in bone marrow stromal cell ligament engineering.

PubMed

Moreau, Jodie E; Chen, Jingsong; Horan, Rebecca L; Kaplan, David L; Altman, Gregory H

2005-01-01

In vitro bone marrow stromal cell (BMSC) growth may be enhanced through culture medium supplementation, mimicking the biochemical environment in which cells optimally proliferate and differentiate. We hypothesize that the sequential administration of growth factors to first proliferate and then differentiate BMSCs cultured on silk fiber matrices will support the enhanced development of ligament tissue in vitro. Confluent second passage (P2) BMSCs obtained from purified bone marrow aspirates were seeded on RGD-modified silk matrices. Seeded matrices were divided into three groups for 5 days of static culture, with medium supplement of basic fibroblast growth factor (B) (1 ng/mL), epidermal growth factor (E; 1 ng/mL), or growth factor-free control (C). After day 5, medium supplementation was changed to transforming growth factor-beta1 (T; 5 ng/mL) or C for an additional 9 days of culture. Real-time RT-PCR, SEM, MTT, histology, and ELISA for collagen type I of all sample groups were performed. Results indicated that BT supported the greatest cell ingrowth after 14 days of culture in addition to the greatest cumulative collagen type I expression measured by ELISA. Sequential growth factor application promoted significant increases in collagen type I transcript expression from day 5 of culture to day 14, for five of six groups tested. All T-supplemented samples surpassed their respective control samples in both cell ingrowth and collagen deposition. All samples supported spindle-shaped, fibroblast cell morphology, aligning with the direction of silk fibers. These findings indicate significant in vitro ligament development after only 14 days of culture when using a sequential growth factor approach.

The Role of Myoepithelial Maspin in Breast Carcinoma Progression Diagnosis and Screening

DTIC Science & Technology

2003-08-01

expression pro- xenografts, the tumors were essentially avascular and their filing (gene chip analysis) to see whether the different myo- 116 S.H. Barskv...factor; aFGF, acidic fibroblast growth factor; TFGa, transforming growth factor a; TGFP3. transforming growth factor 03; TNFa, tumor necrosis factor a...angiogenesis but containing bound angiogenic inhibitors. These myoepithelial xenografts exhibit only minimal hypoxia but extensive necrosis compared with their

Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing

PubMed Central

Koob, Thomas J; Rennert, Robert; Zabek, Nicole; Massee, Michelle; Lim, Jeremy J; Temenoff, Johnna S; Li, William W; Gurtner, Geoffrey

2013-01-01

Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests a paracrine mechanism of action for dHACM when used for wound healing applications. PMID:23902526

Road infrastructure, spatial spillover and county economic growth

NASA Astrophysics Data System (ADS)

Hu, Zhenhua; Luo, Shuang

2017-09-01

This paper analyzes the spatial spillover effect of road infrastructure on the economic growth of poverty-stricken counties, based on the spatial Durbin model, by using the panel data of 37 poor counties in Hunan province from 2006 to 2015. The results showed that there is a significant spatial dependence of economic growth in Poor Counties. Road infrastructure has a positive impact on economic growth, and the results will be overestimated without considering spatial factors. Considering the spatial factors, the road infrastructure will promote the economic growth of the surrounding areas through the spillover effect, but the spillover effect is restricted by the distance factor. Capital investment is the biggest factor of economic growth in poor counties, followed by urbanization, labor force and regional openness.

Region-specific role of growth differentiation factor-5 in the establishment of sympathetic innervation.

PubMed

O'Keeffe, Gerard W; Gutierrez, Humberto; Howard, Laura; Laurie, Christopher W; Osorio, Catarina; Gavaldà, Núria; Wyatt, Sean L; Davies, Alun M

2016-02-15

Nerve growth factor (NGF) is the prototypical target-derived neurotrophic factor required for sympathetic neuron survival and for the growth and ramification of sympathetic axons within most but not all sympathetic targets. This implies the operation of additional target-derived factors for regulating terminal sympathetic axon growth and branching. Here report that growth differentiation factor 5 (GDF5), a widely expressed member of the transforming growth factor beta (TGFβ) superfamily required for limb development, promoted axon growth from mouse superior cervical ganglion (SCG) neurons independently of NGF and enhanced axon growth in combination with NGF. GDF5 had no effect on neuronal survival and influenced axon growth during a narrow window of postnatal development when sympathetic axons are ramifying extensively in their targets in vivo. SCG neurons expressed all receptors capable of participating in GDF5 signaling at this stage of development. Using compartment cultures, we demonstrated that GDF5 exerted its growth promoting effect by acting directly on axons and by initiating retrograde canonical Smad signalling to the nucleus. GDF5 is synthesized in sympathetic targets, and examination of several anatomically circumscribed tissues in Gdf5 null mice revealed regional deficits in sympathetic innervation. There was a marked, highly significant reduction in the sympathetic innervation density of the iris, a smaller though significant reduction in the trachea, but no reduction in the submandibular salivary gland. There was no reduction in the number of neurons in the SCG. These findings show that GDF5 is a novel target-derived factor that promotes sympathetic axon growth and branching and makes a distinctive regional contribution to the establishment of sympathetic innervation, but unlike NGF, plays no role in regulating sympathetic neuron survival.

Problem-Solving Test: The Role of Ubiquitination in Epidermal Growth Factor Receptor Trafficking

ERIC Educational Resources Information Center

Szeberenyi, Jozsef

2012-01-01

Terms to be familiar with before you start to solve the test: growth factor signaling, epidermal growth factor, tyrosine protein kinase, tyrosine phosphorylation, ubiquitin, monoubiquitination, polyubiquitination, site-directed mutagenesis, transfection, expression vector, cDNA, immunoprecipitation, SDS-polyacrylamide gel electrophoresis, Western…

Engineering growth factors for regenerative medicine applications.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitchell, Aaron C.; Briquez, Priscilla S.; Hubbell, Jeffrey A.

Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell traffickingmore » behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications.« less

Prohormone convertase and autocrine growth factor mRNAs are coexpressed in small cell lung carcinoma.

PubMed

Rounseville, M P; Davis, T P

2000-08-01

A hallmark of small cell lung carcinoma (SCLC) is the expression of autocrine growth factors such as neurotensin and gastrin-releasing peptide, which bind to cellular receptors and stimulate cell division. The biological activity of autocrine growth factors requires the concurrent expression of prohormone convertases that cleave the growth factors to their active form, suggesting the expression of these genes is linked in SCLCs. RNase protection assays were used to detect the expression of autocrine growth factor and prohormone convertase mRNAs in a panel of lung cancer cell lines. These mRNAs are coexpressed in SCLC and lung carcinoid cell lines, but not in normal lung epithelium or in non-small cell lung cancers. These findings, together with earlier results from our laboratory, suggest the expression of prohormone convertases has an important role in the development and maintenance of the SCLC phenotype and that autocrine growth factor and prohormone convertase genes respond to a common transcriptional activator in SCLC.

Effects of different growth factors and carriers on bone regeneration: a systematic review.

PubMed

Khojasteh, Arash; Behnia, Hossein; Naghdi, Navid; Esmaeelinejad, Mohammad; Alikhassy, Zahra; Stevens, Mark

2013-12-01

The application and subsequent investigations in the use of varied osteogenic growth factors in bone regeneration procedures have grown dramatically over the past several years. Owing to this rapid gain in popularity and documentation, a review was undertaken to evaluate the in vivo effects of growth factors on bone regeneration. Using related key words, electronic databases (Medline, Embase, and Cochrane) were searched for articles published from 1999 to April 2010 to find growth factor application in bone regeneration in human or animal models. A total of 63 articles were matched with the inclusion criteria of this study. Bone morphogenetic protein 2 (BMP-2) was the most studied growth factor. Carriers for the delivery, experimental sites, and methods of evaluation were different, and therefore articles did not come to a general agreement. Within the limitations of this review, BMP-2 may be an appropriate growth factor for osteogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

PubMed

Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

2015-01-01

Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture.

Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression.

PubMed

Chen, Yan; Huang, Shai; Wu, Bo; Fang, Jiankai; Zhu, Minsheng; Sun, Li; Zhang, Lifeng; Zhang, Yongsheng; Sun, Maomin; Guo, Lingling; Wang, Shouli

2017-07-25

Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1. Moreover, transforming growth factor-β1-mediated inhibition of microRNA -196a-3p and activation of neuropilin-2were required for transforming growth factor-β1-induced migration and invasion of breast cancer cells. In addition, neuropilin-2 expression was suppressed in breast tumors, particularly in triple-negative breast cancers. Collectively, our findings strongly indicate that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and patient survival and a potential therapeutic target in metastatic breast cancer.

Mesenchymal Stem Cells Suppress Chronic Rejection in Heterotopic Small Intestine Transplant Rat Models Via Inhibition of CD68, Transforming Growth Factor- β1, and Platelet-Derived Growth Factor Expression.

PubMed

Li, Fuxin; Cao, Jisen; Zhao, Zhicheng; Li, Chuan; Qi, Feng; Liu, Tong

2017-04-01

Mesenchymal stem cells are easy to obtain and expand, with characteristics of low immunogenicity and strong tissue repair capacity. In this study, our aim was to investigate the role of mesenchymal stem cells in chronic immune rejection of heterotopic small intestine transplant in rats. After successfully constructing a rat chronic immune rejection model of heterotopic small intestine transplant, we infused mesenchymal stem cells into the animal recipients. We observed mesenchymal stem cell location in the recipients, recipient survival, pathology changes, and the expression of CD68, transforming growth factor β1, and platelet-derived growth factor C in the donor intestine. Mesenchymal stem cells inhibited the lymphocyte proliferation caused by concanavalin A in vitro. After stem cells were infused into recipients, they were mainly located in the donor intestine, as well as in the spleen and thymus. Recovery after transplant and pathology changes of the donor intestine in rats with stem cell infusion were better than in the control group; however, we observed no differences in survival time, accompanied by downregulated expression of CD68, transforming growth factor β1, and platelet-derived growth factor C. Mesenchymal stem cells, to a certain extent, could inhibit the process of chronic rejection. The mechanisms may include the inhibited function of these cells on lymphocyte proliferation, reduced infiltration of macrophages, and reduced expression of transforming growth factor β1 and platelet-derived growth factor C.

Anti-fibrotic efficacy of nintedanib in pulmonary fibrosis via the inhibition of fibrocyte activity.

PubMed

Sato, Seidai; Shinohara, Shintaro; Hayashi, Shinya; Morizumi, Shun; Abe, Shuichi; Okazaki, Hiroyasu; Chen, Yanjuan; Goto, Hisatsugu; Aono, Yoshinori; Ogawa, Hirohisa; Koyama, Kazuya; Nishimura, Haruka; Kawano, Hiroshi; Toyoda, Yuko; Uehara, Hisanori; Nishioka, Yasuhiko

2017-09-15

Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear. Human monocytes were isolated from the peripheral blood of healthy volunteers. The expression of growth factors and their receptors in fibrocytes was analyzed using ELISA and Western blotting. The effects of nintedanib on the ability of fibrocytes to stimulate lung fibroblasts were examined in terms of their proliferation. The direct effects of nintedanib on the differentiation and migration of fibrocytes were also assessed. We investigated whether nintedanib affected the accumulation of fibrocytes in mouse lungs treated with bleomycin. Human fibrocytes produced PDGF, FGF2, and VEGF-A. Nintedanib and specific inhibitors for each growth factor receptor significantly inhibited the proliferation of lung fibroblasts stimulated by the supernatant of fibrocytes. Nintedanib inhibited the migration and differentiation of fibrocytes induced by growth factors in vitro. The number of fibrocytes in the bleomycin-induced lung fibrosis model was reduced by the administration of nintedanib, and this was associated with anti-fibrotic effects. These results support the role of fibrocytes as producers of and responders to growth factors, and suggest that the anti-fibrotic effects of nintedanib are at least partly mediated by suppression of fibrocyte function.

Promotion of human early embryonic development and blastocyst outgrowth in vitro using autocrine/paracrine growth factors.

PubMed

Kawamura, Kazuhiro; Chen, Yuan; Shu, Yimin; Cheng, Yuan; Qiao, Jie; Behr, Barry; Pera, Renee A Reijo; Hsueh, Aaron J W

2012-01-01

Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although in vitro fertilization-embryo transfer (IVF-ET) is an established procedure, there is no evidence that present culture conditions are optimal for human early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic development in animal models were tested for their ability to improve human early embryo development and blastocyst outgrowth in vitro. We confirmed the expression of key ligand/receptor pairs in cleavage embryos derived from discarded human tri-pronuclear zygotes and in human endometrium. Combined treatment with key embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony-stimulating factor, insulin-like growth factor-1, glial cell-line derived neurotrophic factor, and artemin) in serum-free media promoted >2.5-fold the development of tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3 surplus embryos cultured individually with the key growth factors showed >3-fold increases in the development of 6-8 cell stage embryos to blastocysts and >7-fold increase in the proportion of high quality blastocysts based on Gardner's criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed-to-be-fertilized oocytes were used to perform somatic cell nuclear transfer (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors increased the progression of reconstructed SCNT embryos to >4-cell stage embryos. Growth factor supplementation of serum-free cultures could promote optimal early embryonic development and implantation in IVF-ET and SCNT procedures. This approach is valuable for infertility treatment and future derivation of patient-specific embryonic stem cells.

The in vitro release of cytokines and growth factors from fibrin membranes produced through horizontal centrifugation.

PubMed

Lourenço, Emanuelle Stellet; Mourão, Carlos Fernando de Almeida Barros; Leite, Paulo Emílio Corrêa; Granjeiro, José Mauro; Calasans-Maia, Mônica Diuana; Alves, Gutemberg Gomes

2018-05-01

Platelet-rich fibrin membranes are biomaterials widely used for therapeutic purposes, and canonically produced through the processing of peripheral blood with fixed-angle rotor centrifuges. In this work, we evaluate the in vitro stability and release of cytokines and growth factors when these biomaterials are produced with a horizontal swing-out clinical centrifuge. Membranes produced from the blood of 14 donors were morphologically evaluated by scanning electron microscopy and fluorescence microscopy, and their stability was assessed by photographic recording after incubation in culture medium for up to 28 days. The release of 27 cytokines and growth factors was monitored for three weeks through a multiparametric immunoassay. The fibrin membranes presented complex three-dimensional structure with a high density of nucleated cells. A large release of growth factors [platelet derived growth factor, fibroblastic growth factor (bFGF), and vascular endothelial growth factor] was detected in the first 24 h, followed by time-dependent decay, maintaining significant concentrations after three weeks. Both anti-inflammatory and pro-inflammatory cytokines presented different release peaks, maintaining high rates of elution for up to 21 days. Chemokines of relevance in tissue repair [RANTES, granulocyte colony-stimulating factor (G-CSF)] were also produced in large quantities throughout the experimental period. The present results demonstrate that blood-derived fibrin membranes with high structural stability and cell content can be generated by horizontal centrifugation, being able of a prolonged production/release of growth factors and pro- and anti-inflammatory cytokines. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1373-1380, 2018. © 2018 Wiley Periodicals, Inc.

Modeling environmental influences on child growth in the MAL-ED cohort study: opportunities and challenges.

PubMed

Richard, Stephanie A; McCormick, Benjamin J J; Miller, Mark A; Caulfield, Laura E; Checkley, William

2014-11-01

Although genetics, maternal undernutrition and low birth weight status certainly play a role in child growth, dietary insufficiency and infectious diseases are key risk factors for linear growth faltering during early childhood. A primary goal of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study is to identify specific risk factors associated with growth faltering during the first 2 years of life; however, growth in early childhood is challenging to characterize because growth may be inherently nonlinear with age. In this manuscript, we describe some methods for analyzing longitudinal growth to evaluate both short- and long-term associations between risk factors and growth trajectories over the first 2 years of life across 8 resource-limited settings using harmonized protocols. We expect there will be enough variability within and between sites in the prevalence of risk factors and burden of linear growth faltering to allow us to distinguish some of the key pathways to linear growth faltering in the MAL-ED study. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.

PubMed

Amable, Paola Romina; Carias, Rosana Bizon Vieira; Teixeira, Marcus Vinicius Telles; da Cruz Pacheco, Italo; Corrêa do Amaral, Ronaldo José Farias; Granjeiro, José Mauro; Borojevic, Radovan

2013-06-07

Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 10(6) to 1.9 × 10(6) platelets/μl). Platelets were highly purified, because only <0.3% from the initial red blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF. Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool from different donors with high reproducibility. These findings support the use of PRP in therapies aiming for tissue regeneration, and its content characterization will allow us to understand and improve the clinical outcomes.

Therapeutic modulation of growth factors and cytokines in regenerative medicine.

PubMed

Ioannidou, Effie

2006-01-01

Regeneration that takes place in the human body is limited throughout life. Therefore, when organs are irreparably damaged, they are usually replaced with an artificial device or donor organ. The term "regenerative medicine" covers the restoration or replacement of cells, tissues, and organs. Stem cells play a major role in regenerative medicine by providing the way to repopulate organs damaged by disease. Stem cells have the ability to self renew and to regenerate cells of diverse lineages within the tissue in which they reside. Stem cells could originate from embryos or adult tissues. Growth factors are proteins that may act locally or systemically to affect the growth of cells in several ways. Various cell activities, including division, are influenced by growth factors. Cytokines are a family of low-molecular-weight proteins that are produced by numerous cell types and are responsible for regulating the immune response, inflammation, tissue remodeling and cellular differentiation. Target cells of growth factors and cytokines are mesenchymal, epithelial and endothelial cells. These molecules frequently have overlapping activities and can act in an autocrine or paracrine fashion. A complex network of growth factors and cytokines guides cellular differentiation and regeneration in all organs and tissues. The aim of this paper is to review the role of growth factors and cytokines in different organs or systems and explore their therapeutic application in regenerative medicine. The role of stem cells combined with growth factors and cytokines in the regeneration of vascular and hematopoietic, neural, skeletal, pancreatic, periodontal, and mucosal tissue is reviewed. There is evidence that supports the use of growth factors and cytokines in the treatment of neurological diseases, diabetes, cardiovascular disease, periodontal disease, cancer and its complication, oral mucositis. After solving the ethical issues and establishing clear and reasonable regulations, regenerative medicine through stem cell application combined with specific growth factors and cytokines will have great potential in curing a variety of human diseases.

The Molecular Epidemiology of Malaria in Western Kenya

DTIC Science & Technology

2002-09-01

including tumor necrosis factor alpha (TNF- α), interleukin-10 (IL-10), transforming growth factor beta (TGF-β), interleukin-6 (IL-6), and interferon gamma...Ricard S, Troesch A, Mallet C, Generenaz L, Evans A, Arveiler D, Luc G, Ruidavets JB, Poirier O. Polymorphisms of the transforming growth factor- beta 1...transforming growth factor- beta 1 and tumour necrosis factor-alpha genes: a technical report. Transpl Immunol 1998 6(3): 193-7. 36. Olomolaiye OO

Colon cancer cells adopt an invasive phenotype without mesenchymal transition in 3-D but not 2-D culture upon combined stimulation with EGF and crypt growth factors.

PubMed

Ludwig, Kirsten; Tse, Edison S; Wang, Jean Yj

2013-05-02

The intestinal crypt homeostasis is maintained by a combination of growth factors including Wnt, R-Spondin1, Noggin and the epidermal growth factor (EGF). In human colorectal cancer, the Wnt pathway is constitutively activated through genetic and epigenetic alterations in as many as 11 genes encoding components of this crypt stem-cell maintenance mechanism. Although the proliferation of colon cancer cells does not require Wnt, it is possible that colon cancer cells can still respond to the crypt growth factors in the colonic microenvironment. A number of studies have shown that epithelial cells behave differently in 3-D versus 2-D cultures. Because the 3-D conditions more closely mimic the in vivo environment, we examined the effects of Wnt and other crypt growth factors on colon cancer cell growth in 3-D culture. Colon cancer cells were grown in 3-D matrigel supplemented with different combinations of crypt growth factors and colonies were examined for morphology and pathways. When colon cancer cells were cultured in 3-D with EGF, they grew as round spheroid colonies. However, colon cancer cells also grew as flat, disc-like colonies when cultured with EGF plus Wnt, R-Spondin1 and Noggin. Disc colonies were found to have comparable levels of E-cadherin as the spheroid colonies, but showed decreased E-cadherin at the cell-matrix contact sites. Disc colonies also elaborated F-actin rich protrusions (FRP) at the cell-matrix edge, reminiscent of an invasive phenotype but without the expression of vimentin. These E-cadherin and F-actin alterations were not induced by the four growth factors in 2-D culture. Formation of the disc colonies was inhibited by the knockdown of β-catenin and by protein kinase inhibitors such as gefitinib, imatinib and MK-2206. Furthermore, withdrawal of the crypt growth factors was able to revert the disc colonies to spheroid growth, showing that the invasive phenotype was reversible dependent on the availability of growth factors. These findings show that colon cancer cells remain responsive to the growth factors in the crypt microenvironment and can be induced to undergo morphological transformation in the more physiologically relevant 3-D culture.

Cloning of a cancer cell-producing hepatocyte growth factor, vascular endothelial growth factor, and interleukin-8 from gastric cancer cells.

PubMed

Iwai, Mineko; Matsuda, Masahiko; Iwai, Yoshiaki

2003-01-01

A cell colony (IM95m) that produces hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) was cloned from gastric cancer cells (IM95 cell line). In culture medium, the highest levels of HGF, VEGF, and IL-8 were about 1.1, 0.9, and 0.17 ng/ml culture medium at 3 d from 10(5) cells. IM95m may be useful in elucidating the role of tumor cells in angiogenesis.

Comparison and evaluation of gene therapy and epigenetic approaches for wound healing.

PubMed

Cutroneo, K R; Chiu, J F

2000-01-01

During the past decade considerable evidence has mounted concerning the importance of growth factors in the wound healing process both for cell replication and for stimulating reparative cells to synthesize and secrete extracellular matrix components. During normal wound healing the growth factor concentration has to be maintained at a certain level. If the growth factor concentration is too low, normal healing fails to occur. Whereas if the growth factor concentration is too high due to either over-expression of the growth factor or too much growth factor being applied to the wound, aberrant wound healing will occur. One approach for controlling the amount of growth factor at the wound site during normal healing is through gene therapy and the titration of gene dosage. However if a narrow window exists between the beneficial therapeutic effect and toxic effects with increasing gene dosage, an agent may be necessary to give in combination with gene therapy to regulate the over-expression of growth factor. In addition to genetic approaches to regulate wound healing, epigenetic approaches also exist. Antisense oligodeoxynucleotides have been shown to regulate wound repair in certain model systems and to determine the protein(s) necessary for normal wound healing. A novel approach to regulate the activity of collagen genes, thereby affecting fibrosis, is to use a sense oligodeoxynucleotide having the same sequence of the cis element which regulates the promoter activity of a particular collagen gene. This exogenous oligodeoxynucleotide will compete with the cis element in the collagen gene for the trans-acting factor which regulates promoter activity. These epigenetic approaches afford the opportunity to regulate over-expression of growth factor and therefore preclude the potential toxic effects of gene therapy. Both genetic and epigenetic approaches for regulating the wound healing process, either normal or aberrant wound healing, have certain advantages and disadvantages which are discussed in the present article.

Growth factor-functionalized silk membranes support wound healing in vitro.

PubMed

Bienert, M; Hoss, M; Bartneck, M; Weinandy, S; Böbel, M; Jockenhövel, S; Knüchel, R; Pottbacker, K; Wöltje, M; Jahnen-Dechent, W; Neuss, S

2017-08-16

Chronic wounds represent a serious problem in daily medical routine requiring improved wound care. Silk of the domesticated silkworm (Bombyx mori) has been used to form a variety of biomaterials for medical applications. We genetically engineered B. mori to produce silk functionalized with growth factors to promote wound healing in vitro. In this study FGF-, EGF-, KGF-, PDGF- or VEGF-functionalized silk membranes were compared to native B. mori silk membranes without growth factors for their ability to support wound healing in vitro. All silk membranes were cytocompatible and supported macrophage secretion of neutrophil recruiting factor CXCL1 and monocyte chemoattractant protein 1 (MCP-1). VEGF-functionalized silk significantly outperformed other growth factor-functionalized silk membranes, but not native silk in angiogenesis assays. In addition, EGF- and VEGF-functionalized silk membranes slightly enhanced macrophage adhesion compared to silk without growth factors. In wound healing assays in vitro (reduction of wound lesion), dermal equivalents showed a higher wound healing capacity when covered with EGF-, FGF- or VEGF-functionalized silk membranes compared to native, KGF- or PDGF-functionalized silk membranes. Keratinocyte migration and growth is overstimulated by KGF- and VEGF-functionalized silk membranes. In conclusion, growth factor-functionalized silk membranes prepared from genetically engineered silk worm glands are promising wound dressings for future wound healing therapies.

Modular control of endothelial sheet migration

PubMed Central

Vitorino, Philip; Meyer, Tobias

2008-01-01

Growth factor-induced migration of endothelial cell monolayers enables embryonic development, wound healing, and angiogenesis. Although collective migration is widespread and therapeutically relevant, the underlying mechanism by which cell monolayers respond to growth factor, sense directional signals, induce motility, and coordinate individual cell movements is only partially understood. Here we used RNAi to identify 100 regulatory proteins that enhance or suppress endothelial sheet migration into cell-free space. We measured multiple live-cell migration parameters for all siRNA perturbations and found that each targeted protein primarily regulates one of four functional outputs: cell motility, directed migration, cell–cell coordination, or cell density. We demonstrate that cell motility regulators drive random, growth factor-independent motility in the presence or absence of open space. In contrast, directed migration regulators selectively transduce growth factor signals to direct cells along the monolayer boundary toward open space. Lastly, we found that regulators of cell–cell coordination are growth factor-independent and reorient randomly migrating cells inside the sheet when boundary cells begin to migrate. Thus, cells transition from random to collective migration through a modular control system, whereby growth factor signals convert boundary cells into pioneers, while cells inside the monolayer reorient and follow pioneers through growth factor-independent migration and cell–cell coordination. PMID:19056882

Biomimetic hybrid porous scaffolds immobilized with platelet derived growth factor-BB promote cellularization and vascularization in tissue engineering.

PubMed

Murali, Ragothaman; Ponrasu, Thangavel; Cheirmadurai, Kalirajan; Thanikaivelan, Palanisamy

2016-02-01

Development of hybrid scaffolds with synergistic combination of growth factor is a promising approach to promote early in vivo wound repair and tissue regeneration. Here, we show the rapid wound healing in Wistar albino rats using biomimetic collagen-poly(dialdehyde) guar gum based hybrid porous scaffolds covalently immobilized with platelet derived growth factor-BB. The immobilized platelet derived growth factor in the hybrid scaffolds not only enhance the total protein, collagen, hexosamine, and uronic acid contents in the granulation tissue but also provide stronger tissues. The wound closure analysis reveal that the complete epithelialization period is 15.4 ± 0.9 days for collagen-poly(dialdehyde) guar gum-platelet derived growth factor hybrid scaffolds, whereas it is significantly higher for control, collagen, collagen- poly(dialdehyde) guar gum and povidine-iodine treated groups. Further, the histological evaluation shows that the immobilized platelet derived growth factor in the hybrid scaffolds induced a more robust cellular and vascular response in the implanted site. Hence, we demonstrate that the collagen-poly(dialdehyde) guar gum hybrid scaffolds loaded with platelet derived growth factor stimulates chemotactic effects in the implanted site to promote rapid tissue regeneration and wound repair without the assistance of antibacterial agents. © 2015 Wiley Periodicals, Inc.

Old friends in new constellations--the hematopoetic growth factors G-CSF, GM-CSF, and EPO for the treatment of neurological diseases.

PubMed

Maurer, M H; Schäbitz, W-R; Schneider, A

2008-01-01

Currently, growth factors which have been identified in hematopoiesis and angiogenesis are re-considered as therapeutical agents in a number of neurological diseases, mainly neurodegenerative disorders like Parkinson's Disease, amyotrophic lateral sclerosis (ALS), or cerebrovascular events such as stroke. Among these growth factors, erythropoietin (EPO) and granulocyte colony-stimulating growth factor (G-CSF) are the most prominent. With regard to neurological disease, EPO has been tested in clinical trials for potential use in stroke, schizophrenia, and addiction, G-CSF is currently under clinical investigation for stroke treatment. The major advantage of these growth factors is their well-described pharmacological behavior and their clinical use over several years. A number of mechanisms of action in the CNS have been identified that are probably important for the beneficial action of these factors in animal models of disease, the most relevant relating to neuroprotection, neuroplasticity and stem cell growth and differentiation. In this review, we will discuss the current efforts and prerequisites of novel growth factor therapies for neurodegenerative diseases with regard to their possible mechanism of action on the molecular level and their effects on brain-derived stem cell populations. Additionally, we will describe the necessities for future research before such therapies can be envisioned.

Release of Growth Factors into Root Canal by Irrigations in Regenerative Endodontics.

PubMed

Zeng, Qian; Nguyen, Sean; Zhang, Hongming; Chebrolu, Hari Priya; Alzebdeh, Dalia; Badi, Mustafa A; Kim, Jong Ryul; Ling, Junqi; Yang, Maobin

2016-12-01

The aim of this study was to investigate the release of growth factors into root canal space after the irrigation procedure of regenerative endodontic procedure. Sixty standardized root segments were prepared from extracted single-root teeth. Nail varnish was applied to all surfaces except the root canal surface. Root segments were irrigated with 1.5% NaOCl + 17% EDTA, 2.5% NaOCl + 17% EDTA, 17% EDTA, or deionized water. The profile of growth factors that were released after irrigation was studied by growth factor array. Enzyme-linked immunosorbent assay was used to validate the release of transforming growth factor (TGF)-β1 and basic fibroblast growth factor (bFGF) at 4 hours, 1 day, and 3 days after irrigation. The final concentrations were calculated on the basis of the root canal volume measured by cone-beam computed tomography. Dental pulp stem cell migration on growth factors released from root segments was measured by using Transwell assay. Total of 11 of 41 growth factors were detected by growth factors array. Enzyme-linked immunosorbent assay showed that TGF-β1 was released in all irrigation groups. Compared with the group with 17% EDTA (6.92 ± 4.49 ng/mL), the groups with 1.5% NaOCl + 17% EDTA and 2.5% NaOCl + 17% EDTA had significantly higher release of TGF-β1 (69.04 ± 30.41 ng/mL and 59.26 ± 3.37 ng/mL, respectively), with a peak release at day 1. The release of bFGF was detected at a low level in all groups (0 ng/mL to 0.43 ± 0.22 ng/mL). Migration assay showed the growth factors released from root segments induced dental pulp stem cell migration. The root segment model in present study simulated clinical scenario and indicated that the current irrigation protocol released a significant amount of TGF-β1 but not bFGF. The growth factors released into root canal space induced dental pulp stem cell migration. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of nerve growth factor for the treatment of neurological diseases: a meta-analysis of 64 randomized controlled trials involving 6,297 patients

PubMed Central

Zhao, Meng; Li, Xiao-yan; Xu, Chun-ying; Zou, Li-ping

2015-01-01

OBJECTIVE: China is the only country where nerve growth factor is approved for large-scale use as a clinical medicine. More than 10 years ago, in 2003, nerve growth factor injection was listed as a national drug. The goal of this article is to evaluate comprehensively the efficacy and safety of nerve growth factor for the treatment of neurological diseases. DATA RETRIEVAL: A computer-based retrieval was performed from six databases, including the Cochrane Library, PubMed, EMBASE, Sino Med, CNKI, and the VIP database, searching from the clinical establishment of nerve growth factor for treatment until December 31, 2013. The key words for the searches were “nerve growth factor, randomized controlled trials” in Chinese and in English. DATA SELECTION: Inclusion criteria: any study published in English or Chinese referring to randomized controlled trials of nerve growth factor; patients with neurological diseases such as peripheral nerve injury, central nerve injury, cranial neuropathy, and nervous system infections; patients older than 7 years; similar research methods and outcomes assessing symptoms; and measurement of nerve conduction velocities. The meta-analysis was conducted using Review Manager 5.2.3 software. MAIN OUTCOME MEASURES: The total effective rate, the incidence of adverse effects, and the nerve conduction velocity were recorded for each study. RESULTS: Sixty-four studies involving 6,297 patients with neurological diseases were included. The total effective rate in the group treated with nerve growth factor was significantly higher than that in the control group (P < 0.0001, RR: 1.35, 95%CI: 1.30–1.40). The average nerve conduction velocity in the nerve growth factor group was significantly higher than that in the control group (P < 0.00001, MD: 4.59 m/s, 95%CI: 4.12–5.06). The incidence of pain or scleroma at the injection site in the nerve growth factor group was also higher than that in the control group (P < 0.00001, RR: 6.30, 95%CI: 3.53–11.27), but such adverse effects were mild. CONCLUSION: Nerve growth factor can significantly improve nerve function in patients with nervous system disease and is safe and effective. PMID:26109961

Understanding the role of growth factors in embryonic development: insights from the lens

PubMed Central

Lovicu, F. J.; McAvoy, J. W.; de Iongh, R. U.

2011-01-01

Growth factors play key roles in influencing cell fate and behaviour during development. The epithelial cells and fibre cells that arise from the lens vesicle during lens morphogenesis are bathed by aqueous and vitreous, respectively. Vitreous has been shown to generate a high level of fibroblast growth factor (FGF) signalling that is required for secondary lens fibre differentiation. However, studies also show that FGF signalling is not sufficient and roles have been identified for transforming growth factor-β and Wnt/Frizzled families in regulating aspects of fibre differentiation. In the case of the epithelium, key roles for Wnt/β-catenin and Notch signalling have been demonstrated in embryonic development, but it is not known if other factors are required for its formation and maintenance. This review provides an overview of current knowledge about growth factor regulation of differentiation and maintenance of lens cells. It also highlights areas that warrant future study. PMID:21402581

The use of autologous blood-derived growth factors in bone regeneration

PubMed Central

Civinini, Roberto; Macera, Armando; Nistri, Lorenzo; Redl, Birgit; Innocenti, Massimo

2011-01-01

Platelet-rich plasma (PRP) is defined as a portion of the plasma fraction of autologous blood having platelet concentrations above baseline. When activated the platelets release growth factors that play an essential role in bone healing such as Platelet-derived Growth Factor, Transforming Growth Factor-β, Vascular Endothelial Growth Factor and others. Multiple basic science and in vivo animal studies agree that PRP has a role in the stimulation of the healing cascade in ligament, tendon, muscle cartilage and in bone regeneration in the last years PRP had a widespread diffusion in the treatment of soft tissue and bone healing. The purpose of this review is to describe the biological properties of platelets and its factors, the methods used for producing PRP, to provide a background on the underlying basic science and an overview of evidence based medicine on clinical application of PRP in bone healing. PMID:22461800

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

PubMed

De Leonibus, C; Chatelain, P; Knight, C; Clayton, P; Stevens, A

2016-11-01

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children

PubMed Central

De Leonibus, C; Chatelain, P; Knight, C; Clayton, P; Stevens, A

2016-01-01

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene–environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene–environment interactions in children treated with r-hGH. PMID:26503811

NEUROTROPHIC FACTORS IN COMBINATORIAL APPROACHES FOR SPINAL CORD REGENERATION

PubMed Central

McCall, Julianne; Weidner, Norbert; Blesch, Armin

2012-01-01

Axonal regeneration is inhibited by a plethora of different mechanisms in the adult central nervous system (CNS). While neurotrophic factors have been shown to stimulate axonal growth in numerous animal models of nervous system injury, a lack of suitable growth substrates, an insufficient activation of neuron-intrinsic regenerative programs and extracellular inhibitors of regeneration limit the efficacy of neurotrophic factor delivery for anatomical and functional recovery after spinal cord injury. Thus, growth-stimulating factors will likely have to be combined with other treatment approaches to tap into the full potential of growth factor therapy for axonal regeneration. In addition, the temporal and spatial distribution of growth factors have to be tightly controlled to achieve biologically active concentrations, to allow for the chemotropic guidance of axons and to prevent adverse effects related to the widespread distribution of neurotrophic factors. Here, we will review the rationale for combinatorial treatments in axonal regeneration and summarize some recent progress in promoting axonal regeneration in the injured CNS using such approaches. PMID:22526621

Cytokine concentration in aqueous humor of eyes with diabetic macular edema.

PubMed

Jonas, Jost B; Jonas, Rahul A; Neumaier, Michael; Findeisen, Peter

2012-01-01

To measure cytokine concentrations in aqueous humor of eyes with diffuse diabetic macular edema. The interventional clinical comparative study included a study group of 23 patients with diffuse diabetic macular edema and a control group of 22 patients undergoing cataract surgery. Cytokine concentrations were measured in aqueous humor samples using a Luminex xMAP suspension array technology. In the study group as compared with the control group, significantly higher concentrations were measured for epidermal growth factor (P < 0.001), human growth factor (P < 0.001), intercellular adhesion molecule-1 (ICAM-1; P < 0.001), interleukin (IL)-1a2 (P = 0.04), IL-6 (P = 0.001), IL-8 (P < 0.001), interferon gamma-induced protein (P = 0.004), monocyte chemoattractant protein-1 (P < 0.001), monokine induced by interferon gamma (P < 0.001), matrix metalloproteinase 1 (P = 0.02), matrix metalloproteinase 9 (P < 0.001), plasminogen activator inhibitor 1 (P < 0.001), placenta growth factor (P < 0.001), tissue growth factor beta (P = 0.003), vascular cell adhesion molecule (P < 0.001), and vascular endothelial growth factor (P < 0.001). Retinal macula thickness was significantly associated with the concentrations of the epidermal growth factor (P = 0.005; ρ = 0.45), ICAM-1 (P < 0.001; ρ = 0.65), IL-3 (P = 0.002; ρ = 0.48), IL-6 (P = 0.003; ρ = 0.47), IL-8 (P < 0.001; ρ = 0.71), monocyte chemoattractant protein-1 (P = 0.001; ρ = 0.53), monokine induced by interferon gamma (P < 0.001; ρ = 0.57), matrix metalloproteinase 9 (P < 0.001; ρ = 0.61), tissue growth factor beta (P = 0.01; ρ = 0.42), placenta growth factor (P = 0.004; ρ = 0.46), vascular cell adhesion molecule (P = 0.006; ρ = 0.44), and vascular endothelial growth factor (P = 0.01; ρ = 0.42). In multivariate analysis, macular thickness remained to be significantly associated with the concentration of ICAM-1 (P = 0.03; r = 0.30). Vascular endothelial growth factor concentrations were correlated with concentration of placenta growth factor (P < 0.001; ρ = 0.78), plasminogen activator inhibitor 1 (P = 0.001; ρ = 0.54), ICAM-1 (P < 0.001; ρ = 0.47), monokine induced by interferon gamma (P = 0.004; ρ = 0.44), monocyte chemoattractant protein-1 (P = 0.003; ρ = 0.43), vascular cell adhesion molecule (P = 0.01; ρ = 0.38), IL-6 (P = 0.02; ρ = 0.35), IL-8 (P = 0.02; ρ = 0.37), epidermal growth factor (P = 0.01; ρ = 0.39), and macrophage migration inhibitory factor (P = 0.01; ρ = 0.37). Numerous cytokines are associated with the presence and the amount of diabetic macular edema. Among these cytokines, ICAM-1 was the most significantly associated with the disease parameters.

Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation on Tumor-Associated Endothelial Cells Leads to Treatment of Orthotopic Human Colon Cancer in Nude Mice1

PubMed Central

Sasaki, Takamitsu; Kitadai, Yasuhiko; Nakamura, Toru; Kim, Jang-Seong; Tsan, Rachel Z; Kuwai, Toshio; Langley, Robert R; Fan, Dominic; Kim, Sun-Jin; Fidler, Isaiah J

2007-01-01

The purpose of our study was to determine whether the dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways in tumor-associated endothelial cells can inhibit the progressive growth of human colon carcinoma in the cecum of nude mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in the cecum of nude mice expressed a high level of transforming growth factor alpha (TGF-α) and vascular endothelial growth factor (VEGF) but were negative for EGFR, human epidermal growth factor receptor 2 (HER2), and VEGFR. Double immunofluorescence staining revealed that tumor-associated endothelial cells expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR), and phosphorylated VEGFR (pVEGFR). Treatment of mice with either 7H-pyrrolo [2,3-d]-pyrimidine lead scaffold (AEE788; an inhibitor of EGFR and VEGFR tyrosine kinase) or CPT-11 as single agents significantly inhibited the growth of cecal tumors (P < .01); this decrease was even more pronounced with AEE788 combined with CPT-11 (P < .001). AEE788 alone or combined with CPT-11 also inhibited the expression of pEGFR and pVEGFR on tumor-associated endothelial cells, significantly decreased vascularization and tumor cell proliferation, and increased the level of apoptosis in both tumor-associated endothelial cells and tumor cells. These data demonstrate that targeting EGFR and VEGFR signaling on tumor-associated endothelial cells provides a viable approach for the treatment of colon cancer. PMID:18084614

Vascular Endothelial Growth Factor (VEGF) and Platelet (PF-4) Factor 4 Inputs Modulate Human Microvascular Endothelial Signaling in a Three-Dimensional Matrix Migration Context*

PubMed Central

Hang, Ta-Chun; Tedford, Nathan C.; Reddy, Raven J.; Rimchala, Tharathorn; Wells, Alan; White, Forest M.; Kamm, Roger D.; Lauffenburger, Douglas A.

2013-01-01

The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial postwound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage before progression of wound healing toward tissue homeostasis. Because of its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 h of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment. PMID:24023389

Role of Autophagy in Keratin Homeostasis in Breast Cancer

DTIC Science & Technology

2014-03-01

weaning of pups, involution commences where the mammary gland reverts to its pre- pregnant state (Brisken and O’Malley, 2010). Pubertal mouse mammary...estrogen, progesterone and prolactin and local growth factors such as Insulin growth factor-1 (IGF-1), Hepatocyte growth factor (HGF), and Fibroblast growth...lentiviral  infection.    Following  infection,   resistant  colonies   were  allowed  to  emerge  and  independent  colonies

Multifunctional mesoporous bioactive glasses for effective delivery of therapeutic ions and drug/growth factors.

PubMed

Wu, Chengtie; Chang, Jiang

2014-11-10

Regeneration of large-size bone defects represents a significant challenge clinically, which requires the use of scaffolds with multifunction, such as anti-bacterial activity, and stimulation of osteogenesis and angiogenesis. It is known that functional ions or drug/growth factors play an important role to stimulate tissue regeneration. Mesoporous bioactive glasses (MBG) possess excellent bioactivity and drug-delivery ability as well as effective ionic release in the body fluids microenvironment due to its specific mesoporous structure and large surface area. For these reasons, functional ions (e.g. lithium (Li), strontium (Sr), Copper (Cu) and Boron (B)) and drug/growth factors (e.g. dexamethasone, vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)) have been incorporated into MBG, which shows high loading efficiency and effective release. The release of therapeutic ions and drug/growth factors from MBG offers it multifunctional properties, such as improved osteogenesis, angiogenesis, anti-bacterial/cancer activity. However, there is no a systematic review about delivery of therapeutic ions and drugs/growth factors from MBG for the functional effect on the tissue regeneration despite that significant progress has been achieved in the past five years. Therefore, in this review, we mainly focused on the new advances for the functional effect of delivering therapeutic ions and drugs/growth factors on the ostegeogenesis, angiogenesis and antibacterial activity. It is expected that the review will offer new concept to develop multifunctional biomaterials for bone regeneration by the synergistic effect of therapeutic ions and drug/growth factors. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of calcium salts and bovine thrombin on growth factor release from equine platelet-rich gel supernatants.

PubMed

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2017-01-16

To compare five activation methods in equine platelet-rich plasma (PRP) by determination of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) concentrations in platelet-rich gel (PRG) supernatants. Platelet-rich plasma from 20 horses was activated by calcium chloride (CC), calcium gluconate (CG), bovine thrombin (BT), and their combinations, BTCC and BTCG. Both growth factor concentrations in PRG supernatants were measured by ELISA and compared with plasma and platelet lysates (PL) over time. Growth factor concentrations were significantly lower in plasma and higher for all PRG supernatants. Platelet lysates contained a significantly lower concentration of PDGF-BB than PRG supernatants and a significantly higher concentration of TGF-β1 than PRG supernatants. Clots from PRP activated with sodium salts were more stable over time and had significant growth factor release, whereas CC produced gross salt deposition. Significant correlations were noticed for platelet with leukocyte concentrations in PRP (r s : 0.76), platelet counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.86), platelet counts in PRP with PDGF-BB concentrations in PRG supernatants (r s : 0.78), leukocyte counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.76), and PDGF-BB concentrations with activating substances (r s : 0.72). Calcium gluconate was the better substance to induce PRP activation. It induced growth factor release free from calcium precipitates in the clots. Use of BT alone or combined with calcium salts was not advantageous for growth factor release.

Recent Insights into the Regulation of the Growth Plate

PubMed Central

Lui, Julian C.; Nilsson, Ola; Baron, Jeffrey

2014-01-01

For most bones, elongation is driven primarily by chondrogenesis at the growth plates. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion and is carefully orchestrated by complex networks of local paracrine factors and modulated by endocrine factors. We review here recent advances in the understanding of growth plate physiology. These advances include new approaches to study expression patterns of large numbers of genes in the growth plate, using microdissection followed by microarray. This approach has been combined with genome-wide association studies to provide insights into the regulation of the human growth plate. We also review recent studies elucidating the roles of bone morphogenetic proteins, fibroblast growth factors, C-type natriuretic peptide, and suppressor of cytokine signaling in the local regulation of growth plate chondrogenesis and longitudinal bone growth. PMID:24740736

Regulation of cell growth by redox-mediated extracellular proteolysis of platelet-derived growth factor receptor beta.

PubMed

Okuyama, H; Shimahara, Y; Kawada, N; Seki, S; Kristensen, D B; Yoshizato, K; Uyama, N; Yamaoka, Y

2001-07-27

Redox-regulated processes are important elements in various cellular functions. Reducing agents, such as N-acetyl-l-cysteine (NAC), are known to regulate signal transduction and cell growth through their radical scavenging action. However, recent studies have shown that reactive oxygen species are not always involved in ligand-stimulated intracellular signaling. Here, we report a novel mechanism by which NAC blocks platelet-derived growth factor (PDGF)-induced signaling pathways in hepatic stellate cells, a fibrogenic player in the liver. Unlike in vascular smooth muscle cells, we found that reducing agents, including NAC, triggered extracellular proteolysis of PDGF receptor-beta, leading to desensitization of hepatic stellate cells toward PDGF-BB. This effect was mediated by secreted mature cathepsin B. In addition, type II transforming growth factor-beta receptor was also down-regulated. Furthermore, these events seemed to cause a dramatic improvement of rat liver fibrosis. These results indicated that redox processes impact the cell's response to growth factors by regulating the turnover of growth factor receptors and that "redox therapy" is promising for fibrosis-related disease.

Bee Venom Promotes Hair Growth in Association with Inhibiting 5α-Reductase Expression.

PubMed

Park, Seeun; Erdogan, Sedef; Hwang, Dahyun; Hwang, Seonwook; Han, Eun Hye; Lim, Young-Hee

2016-06-01

Alopecia is an important issue that can occur in people of all ages. Recent studies show that bee venom can be used to treat certain diseases including rheumatoid arthritis, neuralgia, and multiple sclerosis. In this study, we investigated the preventive effect of bee venom on alopecia, which was measured by applying bee venom (0.001, 0.005, 0.01%) or minoxidil (2%) as a positive control to the dorsal skin of female C57BL/6 mice for 19 d. Growth factors responsible for hair growth were analyzed by quantitative real-time PCR and Western blot analysis using mice skins and human dermal papilla cells (hDPCs). Bee venom promoted hair growth and inhibited transition from the anagen to catagen phase. In both anagen phase mice and dexamethasone-induced catagen phase mice, hair growth was increased dose dependently compared with controls. Bee venom inhibited the expression of SRD5A2, which encodes a type II 5α-reductase that plays a major role in the conversion of testosterone into dihydrotestosterone. Moreover, bee venom stimulated proliferation of hDPCs and several growth factors (insulin-like growth factor 1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)2 and 7) in bee venom-treated hDPCs dose dependently compared with the control group. In conclusion, bee venom is a potentially potent 5α-reductase inhibitor and hair growth promoter.

Purification and Refolding of Overexpressed Human Basic Fibroblast Growth Factor in Escherichia coli

PubMed Central

Alibolandi, Mona; Mirzahoseini, Hasan

2011-01-01

This work describes the integration of expanded bed adsorption (EBA) and adsorptive protein refolding operations used to recover purified and biologically active human basic fibroblast growth factor from inclusion bodies expressed in E. coli. Insoluble overexpressed human basic fibroblast growth factor has been purified on CM Hyper Z matrix by expanded bed adsorption after isolation and solubilization in 8 M urea. The adsorption was made in expanded bed without clarification steps such as centrifugation. Column refolding was done by elimination of urea and elution with NaCl. The human basic fibroblast growth factor was obtained as a highly purified soluble monomer form with similar behavior in circular dichroism and fluorescence spectroscopy as native protein. A total of 92.52% of the available human basic fibroblast growth factor was recovered as biologically active and purified protein using the mentioned purification and refolding process. This resulted in the first procedure describing high-throughput purification and refolding of human basic fibroblast growth factor in one step and is likely to have the greatest benefit for proteins that tend to aggregate when refolded by dilution. PMID:21837279

Genetic and environmental factors in associations between infant growth and adult cardiometabolic risk profile in twins.

PubMed

Touwslager, Robbert N H; Gielen, Marij; Mulder, Antonius L M; Gerver, Willem J M; Zimmermann, Luc J; Dagnelie, Pieter C; Houben, Alfons J H M; Stehouwer, Coen D A; Derom, Catherine; Vlietinck, Robert; Loos, Ruth J F; Zeegers, Maurice P

2013-10-01

Accelerated infant growth is associated with an altered, mostly adverse adult cardiometabolic risk profile. The importance of genetic and environmental factors to these associations is unclear. The objective was to examine the importance of genetic and environmental factors in the associations between infant growth and adult cardiometabolic risk factors (anthropometric characteristics, lipids, insulin sensitivity, leptin, blood pressure, and fibrinogen) in twins. Cardiometabolic risk factors were assessed in 240 twin pairs (aged 18-34 y) from the East Flanders Prospective Twin Survey. Infant growth was defined as change in weight z score. We regressed intrapair differences in growth during 4 growth windows (0-1, 1-6, 6-12, and 12-24 mo) against intrapair differences in the risk factors in monozygotic and dizygotic twins separately. Within monozygotic twin pairs only, associations between infant growth and most adult lipids, glucose, leptin, and blood pressure (eg, systolic blood pressure: b = 5.95 mm Hg per change in z score, P = 0.01 in monozygotic twins; b = -1.64, P = 0.82 in dizygotic twins from 12 to 24 mo) were found. Within dizygotic twin pairs only, associations between growth and triglycerides and fibrinogen (eg, fibrinogen: b = 0.07 ln mg/dL per change in z score, P = 0.31 in monozygotic twins; b = 0.79, P = 0.01 in dizygotic twins from 0 to 1 mo) were identified. Most associations showed a detrimental effect of accelerated growth, but beneficial associations were also identified (eg, total-to-high-density-lipoprotein cholesterol ratio: b = -0.22 per change in z score from 1 to 6 mo, P = 0.008 in monozygotic twins). Our data showed that environmental factors play a role in the associations between infant growth and most adult lipids, glucose, leptin, and blood pressure, whereas genetic factors are involved regarding triglycerides and fibrinogen.

Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

PubMed

Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

2016-02-01

During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

10-Shogaol, an Antioxidant from Zingiber officinale for Skin Cell Proliferation and Migration Enhancer

PubMed Central

Chen, Chung-Yi; Cheng, Kuo-Chen; Chang, Andy Y; Lin, Ying-Ting; Hseu, You-Cheng; Wang, Hui-Min

2012-01-01

In this work, one of Zingiber officinale components, 10-shogaol, was tested with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, metal chelating ability, and reducing power to show antioxidant activity. 10-Shogaol promoted human normal epidermal keratinocytes and dermal fibroblasts cell growths. 10-Shogaol enhanced growth factor production in transforming growth factor-β (TGF-β), platelet derived growth factor-αβ (PDGF-αβ) and vascular endothelial growth factors (VEGF) of both cells. In the in vitro wound healing assay for 12 or 24 h, with 10-shogaol, the fibroblasts and keratinocytes migrated more rapidly than the vehicle control group. Thus, this study substantiates the target compound, 10-shogaol, as an antioxidant for human skin cell growth and a migration enhancer with potential to be a novel wound repair agent. PMID:22408422

Reduction of relative centrifugation force within injectable platelet-rich-fibrin (PRF) concentrates advances patients' own inflammatory cells, platelets and growth factors: the first introduction to the low speed centrifugation concept.

PubMed

Choukroun, J; Ghanaati, S

2018-02-01

The aim of this study was to analyze systematically the influence of the relative centrifugation force (RCF) on leukocytes, platelets and growth factor release within fluid platelet-rich fibrin matrices (PRF). Systematically using peripheral blood from six healthy volunteers, the RCF was reduced four times for each of the three experimental protocols (I-III) within the spectrum (710-44 g), while maintaining a constant centrifugation time. Flow cytometry was applied to determine the platelets and leukocyte number. The growth factor concentration was quantified 1 and 24 h after clotting using ELISA. Reducing RCF in accordance with protocol-II (177 g) led to a significantly higher platelets and leukocytes numbers compared to protocol-I (710 g). Protocol-III (44 g) showed a highly significant increase of leukocytes and platelets number in comparison to -I and -II. The growth factors' concentration of VEGF and TGF-β1 was significantly higher in protocol-II compared to -I, whereas protocol-III exhibited significantly higher growth factor concentration compared to protocols-I and -II. These findings were observed among 1 and 24 h after clotting, as well as the accumulated growth factor concentration over 24 h. Based on the results, it has been demonstrated that it is possible to enrich PRF-based fluid matrices with leukocytes, platelets and growth factors by means of a single alteration of the centrifugation settings within the clinical routine. We postulate that the so-called low speed centrifugation concept (LSCC) selectively enriches leukocytes, platelets and growth factors within fluid PRF-based matrices. Further studies are needed to evaluate the effect of cell and growth factor enrichment on wound healing and tissue regeneration while comparing blood concentrates gained by high and low RCF.

Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc.

PubMed

Le Maitre, Christine L; Richardson, Stephen M A; Baird, Pauline; Freemont, Anthony J; Hoyland, Judith A

2005-12-01

Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic approach. Copyright 2005 Pathological Society of Great Britain and Ireland.

Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing.

PubMed

Koob, Thomas J; Rennert, Robert; Zabek, Nicole; Massee, Michelle; Lim, Jeremy J; Temenoff, Johnna S; Li, William W; Gurtner, Geoffrey

2013-10-01

Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests a paracrine mechanism of action for dHACM when used for wound healing applications. ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Cycles of Ubiquitination and Deubiquitination Critically Regulate Growth Factor-Mediated Activation of Akt Signaling

PubMed Central

Yang, Wei-Lei; Jin, Guoxiang; Li, Chien-Feng; Jeong, Yun Seong; Moten, Asad; Xu, Dazhi; Feng, Zizhen; Chen, Wei; Cai, Zhen; Darnay, Bryant; Gu, Wei; Lin, Hui-Kuan

2013-01-01

K63-linked ubiquitination of Akt is a posttranslational modification that plays a critical role in growth factor-mediated membrane recruitment and activation of Akt. Although E3 ligases involved in growth factor-induced Akt ubiquitination have been defined, the deubiquitinating enzyme (DUB) that triggers deubiquitination of Akt and the function of Akt deubiquitination remain largely unclear. Here, we showed that CYLD was a DUB for Akt and suppressed growth factor-mediated Akt ubiquitination and activation. CYLD directly removed ubiquitin moieties on Akt under serum-starved conditions. CYLD dissociated from Akt upon growth factor stimulation, thereby allowing E3 ligases to induce ubiquitination and activation of Akt. CYLD deficiency also promoted cancer cell proliferation, survival, glucose uptake and growth of prostate tumors. Our findings reveal the crucial role of cycles of ubiquitination and deubiquitination of Akt in its membrane recruitment and activation, and further identifies CYLD as a molecular switch for these processes. PMID:23300340

Targeting the fibroblast growth factor receptors for the treatment of cancer.

PubMed

Lemieux, Steven M; Hadden, M Kyle

2013-06-01

Receptor tyrosine kinases (RTKs) are transmembrane proteins that play a critical role in stimulating signal transduction cascades to influence cell proliferation, growth, and differentiation and they have also been shown to promote angiogenesis when they are up-regulated or mutated. For this reason, their dysfunction has been implicated in the development of human cancer. Over the past decade, much attention has been devoted to developing inhibitors and antibodies against several classes of RTKs, including vascular endothelial growth factor receptors (VEGFRs), epidermal growth factor receptors (EGFRs), and platelet-derived growth factor receptors (PDGFRs). More recently, interest in the fibroblast growth factor receptor (FGFR) class of RTKs as a drug target for the treatment of cancer has emerged. Signaling through FGFRs is critical for normal cellular function and their dysregulation has been linked to various malignancies such as breast and prostate cancer. This review will focus on the current state of both small molecules and antibodies as FGFR inhibitors to provide insight into their development and future potential as anti-cancer agents.

Dual chain synthetic heparin-binding growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

2012-04-24

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Dual chain synthetic heparin-binding growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

2009-10-06

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Growth factors, muscle function, and doping.

PubMed

Goldspink, Geoffrey; Wessner, Barbara; Tschan, Harald; Bachl, Norbert

2010-03-01

This article discusses the inevitable use of growth factors for enhancing muscle strength and athletic performance. Much effort has been expended on developing a treatment of muscle wasting associated with a range of diseases and aging. Frailty in the aging population is a major socioeconomic and medical problem. Emerging molecular techniques have made it possible to gain a better understanding of the growth factor genes and how they are activated by physical activity. The ways that misuse of growth factors may be detected and verified in athletes and future challenges for detecting manipulation of signaling pathways are discussed. Copyright 2010. Published by Elsevier Inc.

Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

PubMed

Chonchol, Michel; Gitomer, Berenice; Isakova, Tamara; Cai, Xuan; Salusky, Isidro; Pereira, Renata; Abebe, Kaleab; Torres, Vicente; Steinman, Theodor I; Grantham, Jared J; Chapman, Arlene B; Schrier, Robert W; Wolf, Myles

2017-09-07

Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in the HALT-PKD Study A ( n =540; mean eGFR =91±17 ml/min per 1.73 m 2 ) and B ( n =462; mean eGFR =48±12 ml/min per 1.73 m 2 ). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in height-adjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Median (interquartile range) intact fibroblast growth factor 23 was 44 (33-56) pg/ml in HALT-PKD Study A and 69 (50-93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, -3.62; 95% confidence interval, -4.12 to -3.12 versus quartile 1, -2.51; 95% confidence interval, -2.71 to -2.30 ml/min per 1.73 m 2 ; P for trend <0.001; Study B: quartile 4, -3.74; 95% confidence interval, -4.14 to -3.34 versus quartile 1, -2.78; 95% confidence interval, -2.92 to -2.63 ml/min per 1.73 m 2 ; P for trend <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m 2 did not improve risk prediction. Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline. Copyright © 2017 by the American Society of Nephrology.

Extracellular matrix and growth factors in branching morphogenesis

NASA Technical Reports Server (NTRS)

Hardman, P.; Spooner, B. S.

1993-01-01

The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

An approach for using general soil physical condition-root growth relationships to predict seedling growth response to site preparation tillage in loblolly pine plantations

Treesearch

L.A. Morris; K.H. Ludovici; S.J. Torreano; E.A. Carter; M.C. Lincoln; R.E. Will

2006-01-01

Tree seedling root growth rate can be limited by any one of three soil physical factors: mechanical resistance, water potential or soil aeration. All three factors vary with soil water content and, under field conditions, root growth rate will depend on the soil water content as a result of its relationship to each factor. For a specific site, the relationship between...

Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

PubMed

Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

2016-08-01

Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.

The emerging connections between IGF1, the intestinal microbiome, Lactobacillus strains and bone growth.

PubMed

Poinsot, Pierre; Schwarzer, Martin; Peretti, Noël; Leulier, François

2018-07-01

In most animal species, postnatal growth is controlled by conserved insulin/insulin-like growth factor (IGF) signaling. In mammals, juvenile growth is characterized by a longitudinal bone growth resulting from the ossification of the growth plate. This ossification is under IGF1 influence through endocrine and paracrine mechanisms. Moreover, the nutritional status has been largely described as an important factor influencing the insulin/insulin-like growth factor signaling. It is now well established that the gut microbiota modulates the nutrient availability of its host. Hence, studies of the interaction between nutritional status, gut microbiota and bone growth have recently emerged. Here, we review recent findings using experimental models about the impact of gut bacteria on the somatotropic axis and its consequence on the bone growth. We also discuss the perspectives of these studies in opening an entire field for clinical interventions. © 2018 Society for Endocrinology.

Plant-Produced Human Recombinant Erythropoietic Growth Factors Support Erythroid Differentiation In Vitro

PubMed Central

Musiychuk, Konstantin; Sivalenka, Rajarajeswari; Jaje, Jennifer; Bi, Hong; Flores, Rosemary; Shaw, Brenden; Jones, R. Mark; Golovina, Tatiana; Schnipper, Jacob; Khandker, Luipa; Sun, Ruiqiang; Li, Chang; Kang, Lin; Voskinarian-Berse, Vanessa; Zhang, Xiaokui; Streatfield, Stephen; Hambor, John; Abbot, Stewart

2013-01-01

Clinically available red blood cells (RBCs) for transfusions are at high demand, but in vitro generation of RBCs from hematopoietic stem cells requires significant quantities of growth factors. Here, we describe the production of four human growth factors: erythropoietin (EPO), stem cell factor (SCF), interleukin 3 (IL-3), and insulin-like growth factor-1 (IGF-1), either as non-fused proteins or as fusions with a carrier molecule (lichenase), in plants, using a Tobacco mosaic virus vector-based transient expression system. All growth factors were purified and their identity was confirmed by western blotting and peptide mapping. The potency of these plant-produced cytokines was assessed using TF1 cell (responsive to EPO, IL-3 and SCF) or MCF-7 cell (responsive to IGF-1) proliferation assays. The biological activity estimated here for the cytokines produced in plants was slightly lower or within the range cited in commercial sources and published literature. By comparing EC50 values of plant-produced cytokines with standards, we have demonstrated that all four plant-produced growth factors stimulated the expansion of umbilical cord blood-derived CD34+ cells and their differentiation toward erythropoietic precursors with the same potency as commercially available growth factors. To the best of our knowledge, this is the first report on the generation of all key bioactive cytokines required for the erythroid development in a cost-effective manner using a plant-based expression system. PMID:23517237

Peroxisome proliferator-activated receptor (PPAR)-gamma expression in human vascular smooth muscle cells: inhibition of growth, migration, and c-fos expression by the peroxisome proliferator-activated receptor (PPAR)-gamma activator troglitazone.

PubMed

Benson, S; Wu, J; Padmanabhan, S; Kurtz, T W; Pershadsingh, H A

2000-01-01

This study was conducted to determine whether cultured human coronary artery and aorta vascular smooth muscle (VSM) cells express the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma); whether the thiazolidinedione troglitazone, a ligand for PPARgamma, would inhibit c-fos expression by these cells; and whether troglitazone would inhibit proliferation and migration induced in these cells by mitogenic growth factors. Using immunoblotting and reverse-transcriptase polymerase chain reaction (RT-PCR) techniques, we show that both human aorta and coronary artery VSM cell lines expressed PPARgamma protein and mRNA for both PPARgamma isoforms, PPARgamma1 and PPARgamma2. Immunocytochemical staining localized the PPARgamma protein primarily within the nucleus. Troglitazone inhibited basic fibroblast growth factor and platelet-derived growth factor-BB induced DNA synthesis in a dose-dependent manner and downregulated the growth-factor-induced expression of c-fos. Troglitazone also inhibited the migration of coronary artery VSM cells along a platelet-derived growth factor-BB concentration gradient. These findings demonstrate for the first time the expression and nuclear localization of PPARgamma in human coronary artery and aorta VSM cells. The data also suggest that the downregulation of c-fos expression, growth-factor-induced proliferation, and migration by VSM may, in part, be mediated by activation of the PPARgamma receptor.

Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

PubMed Central

Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

2011-01-01

Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

Effects of Single Vitamin D₃ Injection (200,000 Units) on Serum Fibroblast Growth Factor 23 and Sclerostin Levels in Subjects with Vitamin D Deficiency.

PubMed

Zhang, Dongdong; Seo, Da Hea; Choi, Han Seok; Park, Hye Sun; Chung, Yoon Sok; Lim, Sung Kil

2017-12-01

Vitamin D deficiency remains common in all age groups and affects skeletal and non-skeletal health. Fibroblast growth factor 23 is a bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D homeostasis as a counter regulatory factor. 1,25-Dihydroxyvitamin D stimulates fibroblast growth factor 23 synthesis in bone, while fibroblast growth factor 23 suppresses 1,25-dihydroxyvitamin D production in the kidney. The aim of this study was to evaluate the effects of vitamin D₃ intramuscular injection therapy on serum fibroblast growth factor 23 concentrations, and several other parameters associated with bone metabolism such as sclerostin, dickkopf-1, and parathyroid hormone. A total of 34 subjects with vitamin D deficiency (defined by serum 25-hydroxyvitamin D levels below 20 ng/mL) were randomly assigned to either the vitamin D injection group (200,000 units) or placebo treatment group. Serum calcium, phosphate, urine calcium/creatinine, serum 25-hydroxyvitamin D, fibroblast growth factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were serially measured after treatment. Comparing the vitamin D injection group with the placebo group, no significant changes were observed in serum fibroblast growth factor 23, parathyroid hormone, or dickkopf-1 levels. Serum sclerostin concentrations transiently increased at week 4 in the vitamin D group. However, these elevated levels declined later and there were no statistically significant differences as compared with baseline levels. Serum fibroblast factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were not affected significantly by single intramuscular injection of vitamin D₃. Copyright © 2017 Korean Endocrine Society

Fibroblast migration and proliferation during in vitro wound healing. A quantitative comparison between various growth factors and a low molecular weight blood dialysate used in the clinic to normalize impaired wound healing.

PubMed

Schreier, T; Degen, E; Baschong, W

1993-01-01

During the formation of granulation tissue in a dermal wound, platelets, monocytes and other cellular blood constituents release various peptide growth factors to stimulate fibroblasts to migrate into the wound site and proliferate, in order to reconstitute the various connective tissue components. The effect on fibroblast migration and proliferation of these growth factors, and of Solcoseryl (HD), a deproteinized fraction of calf blood used to normalize wound granulation and scar tissue formation, was quantified in vitro. The presence of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and hemodialysate (HD) increased the number of cells in the denuded area, i.e., in the "wound space" of an artificially ruptured monolayer of LM-fibroblasts (mouse lung fibroblasts). When cell proliferation was blocked with Mitomycin C, in the first 24 h all factors, i.e., bFGF, PDGF, TGF-beta and HD, promoted cell migration, whereas after 48 h it became obvious that each factor stimulated both migration and proliferation, each in a characteristic way. The effects were significant and more distinct after 48 h, following the order: PDGF (46%) approximately bFGF (87%) > HD (45%) approximately TGF-beta (40%) > control (62%). The relative contributions of migration after inhibiting proliferation are given in brackets. The modulatory activity of HD was localized in its hydrophilic fraction. It was destroyed by acid hydrolysis. Furthermore, this activity could be blocked by protamine sulfate, an inhibitor blocking peptide growth factor receptor binding.

Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

PubMed Central

Soliman, Ashraf; De Sanctis, Vincenzo; Elalaily, Rania; Bedair, Said

2014-01-01

Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS). The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS. PMID:25538878

77 FR 43290 - Children's Health Insurance Program (CHIP); Final Allotments to States, the District of Columbia...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

... subsequent fiscal years are available to match expenditures under an approved State child health plan for 2... care growth factor and the child population growth factor. The per capita health care growth factor for... National Health Expenditures from the calendar year in which the previous fiscal year ends to the calendar...

FGF growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2012-07-24

The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

Expression of Inapproptriate Cadherins in Human Breast Carcinomas

DTIC Science & Technology

2000-08-01

fibroblast growth factor receptor signaling. * We showed that cadherin 11 acts in a manner... fibroblast growth factor receptor signaling; and that cadherin 11 promotes epithelial cell motility in a manner similar to N-cadherin. 28 N-Cadherin...levels of E-cadherin; and that N- cadherin-dependent motility may be mediated by fibroblast growth factor receptor signaling. 14. SUBJECT TERMS

Interplay between pro-inflammatory cytokines and growth factors in depressive illnesses

PubMed Central

Audet, Marie-Claude; Anisman, Hymie

2013-01-01

The development of depressive disorders had long been attributed to monoamine variations, and pharmacological treatment strategies likewise focused on methods of altering monoamine availability. However, the limited success achieved by treatments that altered these processes spurred the search for alternative mechanisms and treatments. Here we provide a brief overview concerning a possible role for pro-inflammatory cytokines and growth factors in major depression, as well as the possibility of targeting these factors in treating this disorder. The data suggest that focusing on one or another cytokine or growth factor might be counterproductive, especially as these factors may act sequentially or in parallel in affecting depressive disorders. It is also suggested that cytokines and growth factors might be useful biomarkers for individualized treatments of depressive illnesses. PMID:23675319

Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer.

PubMed

Yun, Sumi; Kwak, Yoonjin; Nam, Soo Kyung; Seo, An Na; Oh, Heung-Kwon; Kim, Duck-Woo; Kang, Sung-Bum; Lee, Hye Seung

2018-01-17

Molecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients' survival with CRC. The expression of EGFR ligands, including heparin binding epidermal growth factor like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH). We also evaluated the expression status of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and HER4 using immunohistochemistry and/or silver ISH. Unlike low incidences of TGF (38.1%), betacellulin (7.9%), and EGF (2.1%), HBEGF expression was noted in 62.2% of CRC samples. However, the expression of each EGFR ligand did not reveal significant correlations with survival. The combined analyses of EGFR ligands and EGFR expression indicated that the ligands‒/EGFR+ group showed a significant association with the worst disease-free survival (DFS, p=0.018) and overall survival (OS, p=0.005). It was also an independent, unfavorable prognostic factor for DFS (p=0.026) and OS (p=0.007). Additionally, HER4 nuclear expression, regardless of ligand expression, was an independent, favorable prognostic factor for DFS (p=0.034) and OS (p=0.049), by multivariate analysis. Ligand-independent EGFR overexpression was suggested to have a significant prognostic impact; thus, the expression status of EGFR ligands, in addition to EGFR, might be necessary for predicting patients' outcome in CRC.

Fibroblast growth factor and cyclic AMP (cAMP) synergistically activate gene expression at a cAMP response element.

PubMed Central

Tan, Y; Low, K G; Boccia, C; Grossman, J; Comb, M J

1994-01-01

Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways. Images PMID:7935470

Nuclear receptors in pancreatic tumor cells.

PubMed

Damaskos, Christos; Garmpis, Nikolaos; Karatzas, Theodore; Kostakis, Ioannis D; Nikolidakis, Lampros; Kostakis, Alkiviadis; Kouraklis, Gregory

2014-12-01

This review focuses on nuclear receptors expressed in pancreatic cancer. An extensive search of articles published up to March 2013 was conducted using the MEDLINE database. The key words used were "pancreatic cancer", "molecular receptors" and "growth factors". A total of 112 articles referred to pancreatic cancer, molecular receptors and/or growth factors were included. Receptors of growth factors, such as the epithelial growth factor receptor, insulin-like growth factor-1 receptor, vascular endothelial growth factor receptor and others, such as integrin α5β1, somatostatin receptors, the death receptor 5, claudin, notch receptors, mesothelin receptors, follicle-stimulating hormone receptors, the MUC1 receptor, the adrenomedullin receptor, the farnesoid X receptor, the transferrin receptor, sigma-2 receptors, the chemokine receptor CXCR4, the urokinase plasminogen activator receptor, the ephrine A2 receptor, the GRIA3 receptor, the RON receptor and the angiotensin II receptor AT-1 are expressed in pancreatic tumor cells. These molecules are implicated in tumor growth, apoptosis, angiogenesis, metastasis etc. After identifying the molecular receptors associated with the pancreatic cancer, many more target molecules playing important roles in tumor pathophysiology and senescence-associated signal transduction in cancer cells will be identified. This may have a significant influence on diagnosis, therapy and prognosis of pancreatic cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Growth regulation of the mammalian ocular lens by vitreous humor.

PubMed

Banerjee, A; Parafina, J; Bagchi, M

1992-05-01

Experiments were performed in our laboratory to study the effects of a mammalian 8 kD vitreous humor (VH) factor on the DNA synthesis and mitosis of the epithelial cells of organ cultured rabbit lens. The 8 kD polypeptide factor was purified from mature rabbit vitreous humor by liquid chromatography. Proliferative activities of the epithelial cells of organ cultured lenses were stimulated by 3% rabbit serum. The data from our experiments depicted that the 8 kD VH factor effectively inhibits DNA synthesis and mitosis by the epithelial cells of the organ cultured lens. Our experiments also showed that this 8 kD VH factor can maintain its growth inhibitory activity even when heated for 3 min at 95 degrees C. The growth inhibitory effect of the 8 kD VH factor was dose dependent. Using iodinated vitreal proteins it was demonstrated that the VH proteins are able to enter or bind to lens epithelial cells. The growth inhibitory effect of the 8 kD VH factor was also tested on tissue cultured lens epithelial cells. These experiments showed that the 8 kD VH factor has no growth inhibitory effect on the tissue cultured lens epithelial cells. This experiment has been repeated many times using different concentrations of the factor. These observations suggest that the 8 kD VH factor may have receptors in the lens capsular material (extracellular matrix) and the factor-receptor binding is essential for the growth inhibitory effect.

PDGFRα promoter polymorphisms and expression patterns influence risk of development of imatinib-induced thrombocytopenia in chronic myeloid leukemia: A study from India.

PubMed

Guru, Sameer Ahmad; Mir, Rashid; Bhat, Musadiq; Najar, Imtiyaz; Zuberi, Mariyam; Sumi, Mamta; Masroor, Mirza; Gupta, Naresh; Saxena, Alpana

2017-10-01

Platelet-derived growth factor receptor has been implicated in many malignant and non-malignant diseases. Platelet-derived growth factor receptor-α is a tyrosine kinase and a side target for imatinib, a revolutionary drug for the treatment of chronic myeloid leukemia that has dramatically improved the survival of chronic myeloid leukemia patients. Given the importance of platelet-derived growth factor receptor in platelet development and its inhibition by imatinib, it was intriguing to analyze the role of platelet-derived growth factor receptor-α in relation to imatinib treatment in the development of imatinib-induced thrombocytopenia in chronic myeloid leukemia patients. We hypothesized that two known functional polymorphisms, +68GA insertion/deletion and -909C/A, in the promoter region of the platelet-derived growth factor receptor-α gene may affect the susceptibility of chronic myeloid leukemia patients receiving imatinib treatment to the development of thrombocytopenia. A case-control study was conducted among a cohort of chronic myeloid leukemia patients admitted to the Lok Nayak Hospital, New Delhi, India. A set of 100 patients of chronic myeloid leukemia in chronic phase and 100 age- and sex-matched healthy controls were studied. After initiation of imatinib treatment, the hematological response of chronic myeloid leukemia patients was monitored regularly for 2 years, in which the development of thrombocytopenia was the primary end point. Platelet-derived growth factor receptor-α promoter polymorphisms +68GA ins/del and -909C/A were studied by allele-specific polymerase chain reaction. Platelet-derived growth factor receptor-α messenger RNA expression was evaluated by quantitative real-time polymerase chain reaction. The messenger RNA expression results were expressed as 2 -Δct ± standard deviation. The distribution of +68GA ins/del promoter polymorphism genotypes differed significantly between the thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p < 0.0001). Moreover, +68GA del/del and ins/del genotypes in imatinib-treated chronic myeloid leukemia patients were associated with an increased risk of developing thrombocytopenia, with odds ratios 6.5 (95% confidence interval = 2.02-0.89, p = 0.001) and 6.0 (95% confidence interval = 2.26-15.91, p = 0.0002), respectively. Similarly, -909C/A promoter polymorphism genotype distribution also differed significantly between thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p = 0.02), and a significantly increased risk of imatinib-induced thrombocytopenia was associated with -909C/A polymorphism mutant homozygous (AA) genotypes the odds ratio being 7.7 (95% confidence interval 1.50 to 39.91, p = 0.009). However, no significant risk of imatinib-induced thrombocytopenia was found to be associated with heterozygous genotype (-909C/A) with odds ratio 1.9 (95% confidence interval = 0.86-4.56, p = 1.14). Platelet-derived growth factor receptor-α messenger RNA expression was significantly higher in chronic myeloid leukemia patients compared to controls (p = 0.008). Moreover, patients with imatinib-induced thrombocytopenia had a significantly lower platelet-derived growth factor receptor-α messenger RNA expression, compared to patients without thrombocytopenia (p = 0.01). A differential expression of platelet-derived growth factor receptor-α messenger RNA was observed with respect to different +68 GA ins/del and -909C/A polymorphism genotypes. The +68GA deletion allele and -909A allele were significantly associated with lower expression of platelet-derived growth factor receptor-α messenger RNA. The platelet-derived growth factor receptor-α +68GA del/del, +68GA ins/del, and -909AA genotypes are associated with an increased risk of developing thrombocytopenia in imatinib-treated chronic myeloid leukemia patients. A significantly lower platelet-derived growth factor receptor-α messenger RNA expression accompanies the +68GA deletion allele in an allele dose-dependent manner. Platelet-derived growth factor receptor-α -909AA genotype is also associated with lower expression of platelet-derived growth factor receptor-α. The downregulation of platelet-derived growth factor receptor-α expression may play a causative role in imatinib-induced thrombocytopenia, a common side effect, in the subset of chronic myeloid leukemia patients with platelet-derived growth factor receptor-α +68 GA ins/del, +68 GA del/del, and -909C/A genotypes.

Randomized Clinical Trial of Sevelamer Carbonate on Serum Klotho and Fibroblast Growth Factor 23 in CKD.

PubMed

Liabeuf, Sophie; Ryckelynck, Jean-Philippe; El Esper, Najeh; Ureña, Pablo; Combe, Christian; Dussol, Bertrand; Fouque, Denis; Vanhille, Philippe; Frimat, Luc; Thervet, Eric; Mentaverri, Romuald; Prié, Dominique; Choukroun, Gabriel

2017-12-07

Epidemiologic studies suggest that higher serum phosphaturic hormone fibroblast growth factor 23 levels are associated with increase morbidity and mortality. The aim of the FGF23 Reduction Efficacy of a New Phosphate Binder in CKD Trial was to evaluate the effect of sevelamer carbonate on serum C-terminal fibroblast growth factor 23 levels in normophosphatemic patients with CKD stage 3b/4. Patients with CKD, eGFR between 45 and 15 ml/min per 1.73 m 2 , fasting serum phosphate concentration >3.1 mg/dl, and serum C-terminal fibroblast growth factor 23 >80 relative units/ml were included in our double-blind, placebo-controlled, randomized multicenter study. All patients received 100,000 IU cholecalciferol at time of randomization. Participants received either placebo or sevelamer carbonate 4.8 g daily during a 12-week period. Biologic parameters, including serum C-terminal fibroblast growth factor 23, intact fibroblast growth factor 23, and α -klotho, were evaluated at baseline and 12 weeks after inclusion. Of 96 screened patients, 78 (mean±SD age: 63±13 years old; 70% men; mean eGFR: 27±9 ml/min per 1.73 m 2 ) met the inclusion criteria. At baseline, mean eGFR was 27±9 ml/min per 1.73 m 2 , mean serum phosphate level was 3.8±0.5 mg/dl, and median (interquartile range) serum C-terminal fibroblast growth factor 23 level was 157 (120-241) relative units/ml. After 12 weeks of treatment, urinary phosphate-to-creatinine ratio fell significantly in the sevelamer group. The sevelamer and placebo groups did not differ significantly in terms of median change in serum C-terminal fibroblast growth factor 23 levels: the median (interquartile range) change was 38 (-13-114) relative units/ml in the placebo group and 37 (-1-101) relative units/ml in the sevelamer group ( P =0.77). There was no significant difference in serum intact fibroblast growth factor 23, α -klotho, or phosphate levels changes between the two groups. Serum total and LDL cholesterol levels fell significantly in the sevelamer group. In our double-blind, placebo-controlled, randomized study performed in normophosphatemic patients with CKD, a 12-week course of sevelamer carbonate significantly reduced phosphaturia without changing serum phosphorus but did not significantly modify serum C-terminal fibroblast growth factor 23 and intact fibroblast growth factor 23 or α -klotho levels. Copyright © 2017 by the American Society of Nephrology.

An interaction between hepatocyte growth factor and its receptor (c-MET) prolongs the survival of chronic lymphocytic leukemic cells through STAT3 phosphorylation: a potential role of mesenchymal cells in the disease.

PubMed

Giannoni, Paolo; Scaglione, Silvia; Quarto, Rodolfo; Narcisi, Roberto; Parodi, Manuela; Balleari, Enrico; Barbieri, Federica; Pattarozzi, Alessandra; Florio, Tullio; Ferrini, Silvano; Corte, Giorgio; de Totero, Daniela

2011-07-01

Chronic lymphocytic leukemia cells are characterized by an apparent longevity in vivo which is lost when they are cultured in vitro. Cellular interactions and factors provided by the microenvironment appear essential to cell survival and may protect leukemic cells from the cytotoxicity of conventional therapies. Understanding the cross-talk between leukemic cells and stroma is of interest for identifying signals supporting disease progression and for developing novel therapeutic strategies. Different cell types, sharing a common mesenchymal origin and representative of various bone marrow components, were used to challenge the viability of leukemic cells in co-cultures and in contact-free culture systems. Using a bioinformatic approach we searched for genes shared by lineages prolonging leukemic cell survival and further analyzed their biological role in signal transduction experiments. Human bone marrow stromal cells, fibroblasts, trabecular bone-derived cells and an osteoblast-like cell line strongly enhanced survival of leukemic cells, while endothelial cells and chondrocytes did not. Gene expression profile analysis indicated two soluble factors, hepatocyte growth factor and CXCL12, as potentially involved. We demonstrated that hepatocyte growth factor and CXCL12 are produced only by mesenchymal lineages that sustain the survival of leukemic cells. Indeed chronic lymphocytic leukemic cells express a functional hepatocyte growth factor receptor (c-MET) and hepatocyte growth factor enhanced the viability of these cells through STAT3 phosphorylation, which was blocked by a c-MET tyrosine kinase inhibitor. The role of hepatocyte growth factor was confirmed by its short interfering RNA-mediated knock-down in mesenchymal cells. The finding that hepatocyte growth factor prolongs the survival of chronic lymphocytic leukemic cells is novel and we suggest that the interaction between hepatocyte growth factor-producing mesenchymal and neoplastic cells contributes to maintenance of the leukemic clone.

An interaction between hepatocyte growth factor and its receptor (c-MET) prolongs the survival of chronic lymphocytic leukemic cells through STAT3 phosphorylation: a potential role of mesenchymal cells in the disease

PubMed Central

Giannoni, Paolo; Scaglione, Silvia; Quarto, Rodolfo; Narcisi, Roberto; Parodi, Manuela; Balleari, Enrico; Barbieri, Federica; Pattarozzi, Alessandra; Florio, Tullio; Ferrini, Silvano; Corte, Giorgio; de Totero, Daniela

2011-01-01

Background Chronic lymphocytic leukemia cells are characterized by an apparent longevity in vivo which is lost when they are cultured in vitro. Cellular interactions and factors provided by the microenvironment appear essential to cell survival and may protect leukemic cells from the cytotoxicity of conventional therapies. Understanding the cross-talk between leukemic cells and stroma is of interest for identifying signals supporting disease progression and for developing novel therapeutic strategies. Design and Methods Different cell types, sharing a common mesenchymal origin and representative of various bone marrow components, were used to challenge the viability of leukemic cells in co-cultures and in contact-free culture systems. Using a bioinformatic approach we searched for genes shared by lineages prolonging leukemic cell survival and further analyzed their biological role in signal transduction experiments. Results Human bone marrow stromal cells, fibroblasts, trabecular bone-derived cells and an osteoblast-like cell line strongly enhanced survival of leukemic cells, while endothelial cells and chondrocytes did not. Gene expression profile analysis indicated two soluble factors, hepatocyte growth factor and CXCL12, as potentially involved. We demonstrated that hepatocyte growth factor and CXCL12 are produced only by mesenchymal lineages that sustain the survival of leukemic cells. Indeed chronic lymphocytic leukemic cells express a functional hepatocyte growth factor receptor (c-MET) and hepatocyte growth factor enhanced the viability of these cells through STAT3 phosphorylation, which was blocked by a c-MET tyrosine kinase inhibitor. The role of hepatocyte growth factor was confirmed by its short interfering RNA-mediated knock-down in mesenchymal cells. Conclusions The finding that hepatocyte growth factor prolongs the survival of chronic lymphocytic leukemic cells is novel and we suggest that the interaction between hepatocyte growth factor-producing mesenchymal and neoplastic cells contributes to maintenance of the leukemic clone. PMID:21486864

Gene expression analysis of growth factor receptors in human chondrocytes in monolayer and 3D pellet cultures

PubMed Central

Witt, Anika; Salamon, Achim; Boy, Diana; Hansmann, Doris; Büttner, Andreas; Wree, Andreas; Bader, Rainer; Jonitz-Heincke, Anika

2017-01-01

The main goal of cartilage repair is to create functional tissue by enhancing the in vitro conditions to more physiological in vivo conditions. Chondrogenic growth factors play an important role in influencing cartilage homeostasis. Insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β1 affect the expression of collagen type II (Col2) and glycosaminoglycans (GAGs) and, therefore, the targeted use of growth factors could make chondrogenic redifferentiation more efficient. In the present study, human chondrocytes were postmortally isolated from healthy articular cartilage and cultivated as monolayer or 3D pellet cultures either under normoxia or hypoxia and stimulated with IGF-1 and/or TGF-β1 to compare the impact of the different growth factors. The mRNA levels of the specific receptors (IGF1R, TGFBR1, TGFBR2) were analyzed at different time points. Moreover, gene expression rates of collagen type 1 and 2 in pellet cultures were observed over a period of 5 weeks. Additionally, hyaline-like Col2 protein and sulphated GAG (sGAG) levels were quantified. Stimulation with IGF-1 resulted in an enhanced expression of IGF1R and TGFBR2 whereas TGF-β1 stimulated TGFBR1 in the monolayer and pellet cultures. In monolayer, the differences reached levels of significance. This effect was more pronounced under hypoxic culture conditions. In pellet cultures, increased amounts of Col2 protein and sGAGs after incubation with TGF-β1 and/or IGF-1 were validated. In summary, constructing a gene expression profile regarding mRNA levels of specific growth factor receptors in monolayer cultures could be helpful for a targeted application of growth factors in cartilage tissue engineering. PMID:28534942

Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair.

PubMed

Agren, M S; Rasmussen, K; Pakkenberg, B; Jørgensen, B

2014-07-01

Autologous platelet-rich fibrin (PRF(®)) is prepared by the automatic Vivostat(®) system. Conflicting results with Vivostat PRF in acute wound healing prompted us to examine its cellular and biomolecular composition. Specifically, platelets, selected growth factors and matrix metalloproteinase (MMP)-9 were quantified using novel analytical methods. Ten healthy non-thrombocytopenic volunteers donated blood for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood and serum procured in parallel served as baseline controls. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays. The number of leucocytes and erythrocytes was reduced (P < 0·001), whereas platelets increased (P < 0·001) in fibrin-I versus whole blood. PRF contained 982 ± 206 × 10(9) platelets/l representing 3·9-fold (P < 0·001) enrichment relative to whole blood. Growth factor abundance in Vivostat PRF and serum was in descending order: transforming growth factor-β1 [5·1-fold higher in PRF than serum, P < 0·001] > platelet-derived growth factor (PDGF)-AB [2·5-fold, P < 0·01] > PDGF-BB [1·6-fold, P < 0·05] > vascular endothelial growth factor > basic fibroblast growth factor [75-fold, P < 0·001]. MMP-9 was reduced 139-fold (P < 0·001) compared with serum, reflecting leucocyte depletion in PRF. The gained knowledge on platelet enrichment and biomolecular constituents may guide clinicians in their optimal use of Vivostat PRF for tissue regenerative applications. © 2013 International Society of Blood Transfusion.

Effects of acidic fibroblast growth factor on cholinergic neurons of nucleus basalis magnocellularis and in a spatial memory task following cortical devascularization.

PubMed

Figueiredo, B C; Piccardo, P; Maysinger, D; Clarke, P B; Cuello, A C

1993-10-01

The ability of acidic fibroblast growth factor to elicit a trophic response in the nervous system of the rat was tested in vitro and in vivo. Treatment of cultured septal cells with acidic fibroblast growth factor resulted in an elongation of glial processes as assessed by immunostaining for glial fibrillary acidic protein. Increased choline acetyltransferase was also observed. The responses to acidic fibroblast growth factor in vivo were studied in rats trained in a spatial memory task, using the Morris water maze. Randomly selected animals were subjected to unilateral cortical devascularization. This lesion results in partial unilateral infarction of the neocortex, and in retrograde degeneration of the nucleus basalis magnocellularis. Animals were tested post-lesion for memory retention and were then killed for morphological studies. Intracerebroventricular administration of acidic fibroblast growth factor (0.6 microgram/h for seven days starting at surgery) prevented the lesion-induced impairment in this test, and reduced the nucleus basalis magnocellularis cholinergic degeneration, as assessed by morphometric choline acetyltransferase-like immunoreactivity and radioenzymatic assay for choline acetyltransferase activity. The preservation of the phenotype of injured cholinergic neurons of the nucleus basalis magnocellularis by acidic fibroblast growth factor was indicated by the maintenance of the cross-sectional area of cell bodies and mean length of neuritic processes one month after surgery. The effect of acidic fibroblast growth factor in non-cholinergic cells remains to be investigated. It is suggested that acidic fibroblast growth factor may alleviate the lesion-induced deficit in the memory retention task by preventing disruption of functional connections between nucleus basalis magnocellularis and intact cortical areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinopathy of prematurity

PubMed Central

Hellström, Ann; Smith, Lois E H; Dammann, Olaf

2015-01-01

The immature retinas of preterm neonates are susceptible to insults that disrupt neurovascular growth, leading to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal–fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identification and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sight-threatening disease and to limit comorbidities with which the disease shares modifiable risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulin-like growth factor 1 and ω-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and inflammation to promote normal growth and limit suppression of neurovascular development. PMID:23782686

[The laboratory evaluation of pathogenic factors under retarded consolidation of fractures of bones of lower extremities].

PubMed

Stogov, V M; Kireeva, E A; Karasev, A G

2014-12-01

The study was carried out to comparatively analyze metabolic profile and content of growth factors in blood serum of patients with retarded consolidation of fractures of bones of lower extremities. The evaluation was applied to concentration of metabolites, growth factors and enzyme activity of blood serum in 13 patients with retarded consolidation of fractures of thigh and shank bones (main group). The comparative group included 14 patients with solid fractures of thigh and shank bones. The analysis established that as compared to patients with solid fractures of bones, in patients with retarded consolidation of fractures blood serum contained reliably higher concentration of triglycerides, products of glycolysis, epidermal growth factor and transforming growth factors TGF-α and TGF-β2. The content of vitamin E and insullin-like growth factor (IGF-1) was decreased The given markers can be labeled as potential markers of diagnostic and prognosis of development of retarded consolidation of fractures.

Anomolous Fatigue Crack Growth Phenomena in High-Strength Steel

NASA Technical Reports Server (NTRS)

Forth, Scott C.; James, Mark A.; Johnston, William M., Jr.; Newman, James C., Jr.

2004-01-01

The growth of a fatigue crack through a material is the result of a complex interaction between the applied loading, component geometry, three-dimensional constraint, load history, environment, material microstructure and several other factors. Previous studies have developed experimental and computational methods to relate the fatigue crack growth rate to many of the above conditions, with the intent of discovering some fundamental material response, i.e. crack growth rate as a function of something. Currently, the technical community uses the stress intensity factor solution as a simplistic means to relate fatigue crack growth rate to loading, geometry and all other variables. The stress intensity factor solution is a very simple linear-elastic representation of the continuum mechanics portion of crack growth. In this paper, the authors present fatigue crack growth rate data for two different high strength steel alloys generated using standard methods. The steels exhibit behaviour that appears unexplainable, compared to an aluminium alloy presented as a baseline for comparison, using the stress intensity factor solution.

Role of Stroma-Derived Extracellular Matrix in Regulation of Growth and Hormonal Responsiveness of Normal and Cancerous Human Breast Epithelium.

DTIC Science & Technology

1998-09-01

and cultured in serum-free media without growth factors, estrogen did not stimulate proliferation of either cell line. Insulin and growth factors (EGF...purchased from ICN Biomedicals, Inc. Nonessential amino acids (NEAA), gentamycin, certified FBS, and insulin were obtained from Life Technologies, Inc...Laboratories, Inc. (Logan, UT). Insulin - like growth factor-I (IGF-I) was purchased from GroPep Pty. Ltd. (Adelaide, Australia). Poly-L- lysine and all

Systemic and Gene Modified Mesenchymal Stem Cell Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2009-05-01

downregulate the expression of growth factors , receptor tyrosine kinases, proteases, and AR both in vitro and in vivo only when the cells express high... growth , and apoptosis as shown in Figure 1A. Downregulation of growth factors , FGF, Mdk, PDGF, Ptn, TGFb1 and TGFb3, tyrosine kinase receptors Ffgr3 and... growth factors and receptor tyrosine kinases mainly in andro- gen-sensitive and AR-overexpressing cells. The effect was more pronounced in Erk, Ras, and

Neurotrophic factors switch between two signaling pathways that trigger axonal growth.

PubMed

Paveliev, Mikhail; Lume, Maria; Velthut, Agne; Phillips, Matthew; Arumäe, Urmas; Saarma, Mart

2007-08-01

Integration of multiple inputs from the extracellular environment, such as extracellular matrix molecules and growth factors, is a crucial process for cell function and information processing in multicellular organisms. Here we demonstrate that co-stimulation of dorsal root ganglion neurons with neurotrophic factors (NTFs) - glial-cell-line-derived neurotrophic factor, neurturin or nerve growth factor - and laminin leads to axonal growth that requires activation of Src family kinases (SFKs). A different, SFK-independent signaling pathway evokes axonal growth on laminin in the absence of the NTFs. By contrast, axonal branching is regulated by SFKs both in the presence and in the absence of NGF. We propose and experimentally verify a Boolean model of the signaling network triggered by NTFs and laminin. Our results demonstrate that NTFs provide an environmental cue that triggers a switch between separate pathways in the cell signaling network.

ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth.

PubMed

Zhao, Jian; Yuan, Xuejun; Frödin, Morten; Grummt, Ingrid

2003-02-01

Phosphorylation of transcription factors by mitogen-activated protein kinase (MAPK) cascades links cell signaling with the control of gene expression. Here we show that growth factors induce rRNA synthesis by activating MAPK-dependent signaling cascades that target the RNA polymerase I-specific transcription initiation factor TIF-IA. Activation of TIF-IA and ribosomal gene transcription is sensitive to PD98059, indicating that TIF-IA is targeted by MAPK in vivo. Phosphopeptide mapping and mutational analysis reveals two serine residues (S633 and S649) that are phosphorylated by ERK and RSK kinases. Replacement of S649 by alanine inactivates TIF-IA, inhibits pre-rRNA synthesis, and retards cell growth. The results provide a link between growth factor signaling, ribosome production, and cell growth, and may have a major impact on the mechanism of cell transformation.

Intracellular processing of epidermal growth factor. I. Acidification of 125I-epidermal growth factor in intracellular organelles.

PubMed

Matrisian, L M; Planck, S R; Magun, B E

1984-03-10

We previously reported that 125I-labeled epidermal growth factor is processed intracellularly to acidic macromolecules in Rat-1 fibroblasts. The present study defines the precursor-product relationship and localization of the processing steps to subcellular organelles by the use of a single isoelectric species of 125I-epidermal growth factor and Percoll gradient fractionation. The native pI 4.55 125I-epidermal growth factor was rapidly processed to a pI 4.2 species on or near the cell surface and in organelles corresponding to clathrin-coated vesicles, Golgi, and endoplasmic reticulum. This species was then processed to a pI 4.35 species in similar organelles. The pI 4.2 and 4.35 species were converted to a pI 4.0 species in dense, lysosome-like organelles. This species was ultimately degraded and exocytosed from the cell as low molecular weight products.

Combination Growth Factor Therapy via Electrostatically Assembled Wound Dressings Improves Diabetic Ulcer Healing In Vivo.

PubMed

Almquist, Benjamin D; Castleberry, Steven A; Sun, Julia B; Lu, Alice Y; Hammond, Paula T

2015-10-01

Chronic skin ulcerations are a common complication of diabetes mellitus, affecting up to one in four diabetic individuals. Despite the prevalence of these wounds, current pharmacologic options for treating them remain limited. Growth factor-based therapies have displayed a mixed ability to drive successful healing, which may be due to nonoptimal delivery strategies. Here, a method for coating commercially available nylon dressings using the layer-by-layer process is described to enable both sustained release and independent control over the release kinetics of vascular endothelial growth factor 165 and platelet-derived growth factor BB. It is shown that the use of strategically spaced diffusion barriers formed spontaneously by disulfide bonds enables independent control over the release rates of incorporated growth factors, and that in vivo these dressings improve several aspects of wound healing in db/db mice. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Minimizing Public Costs of Residential Growth. Coping With Growth.

ERIC Educational Resources Information Center

Weber, Bruce; Beck, Richard

Rapid residential growth in rural areas or on the fringes of urban areas brings both costs and benefits. Seven factors determine whether new homes and subdivisions generate more revenues than expenditures. Local governments can substantially influence four of these seven factors in order to reduce the public costs of residential growth. Less…

A combined model of human erythropoiesis and granulopoiesis under growth factor and chemotherapy treatment

PubMed Central

2014-01-01

Background Haematotoxicity of conventional chemotherapies often results in delays of treatment or reduction of chemotherapy dose. To ameliorate these side-effects, patients are routinely treated with blood transfusions or haematopoietic growth factors such as erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF). For the latter ones, pharmaceutical derivatives are available, which differ in absorption kinetics, pharmacokinetic and -dynamic properties. Due to the complex interaction of cytotoxic effects of chemotherapy and the stimulating effects of different growth factor derivatives, optimal treatment is a non-trivial task. In the past, we developed mathematical models of thrombopoiesis, granulopoiesis and erythropoiesis under chemotherapy and growth-factor applications which can be used to perform clinically relevant predictions regarding the feasibility of chemotherapy schedules and cytopenia prophylaxis with haematopoietic growth factors. However, interactions of lineages and growth-factors were ignored so far. Results To close this gap, we constructed a hybrid model of human granulopoiesis and erythropoiesis under conventional chemotherapy, G-CSF and EPO applications. This was achieved by combining our single lineage models of human erythropoiesis and granulopoiesis with a common stem cell model. G-CSF effects on erythropoiesis were also implemented. Pharmacodynamic models are based on ordinary differential equations describing proliferation and maturation of haematopoietic cells. The system is regulated by feedback loops partly mediated by endogenous and exogenous EPO and G-CSF. Chemotherapy is modelled by depletion of cells. Unknown model parameters were determined by fitting the model predictions to time series data of blood counts and cytokine profiles. Data were extracted from literature or received from cooperating clinical study groups. Our model explains dynamics of mature blood cells and cytokines after growth-factor applications in healthy volunteers. Moreover, we modelled 15 different chemotherapeutic drugs by estimating their bone marrow toxicity. Taking into account different growth-factor schedules, this adds up to 33 different chemotherapy regimens explained by the model. Conclusions We conclude that we established a comprehensive biomathematical model to explain the dynamics of granulopoiesis and erythropoiesis under combined chemotherapy, G-CSF, and EPO applications. We demonstrate how it can be used to make predictions regarding haematotoxicity of yet untested chemotherapy and growth-factor schedules. PMID:24886056

Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion

PubMed Central

Gorin, Caroline; Rochefort, Gael Y.; Bascetin, Rumeyza; Ying, Hanru; Lesieur, Julie; Sadoine, Jérémy; Beckouche, Nathan; Berndt, Sarah; Novais, Anita; Lesage, Matthieu; Hosten, Benoit; Vercellino, Laetitia; Merlet, Pascal; Le-Denmat, Dominique; Marchiol, Carmen; Letourneur, Didier; Nicoletti, Antonino; Vital, Sibylle Opsahl; Poliard, Anne; Salmon, Benjamin; Germain, Stéphane

2016-01-01

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF. Significance The results from the present study show that fibroblast growth factor-2 (FGF-2) priming is more efficient than hypoxia at increasing dental pulp stem cells derived from deciduous teeth (SHED)-induced vascularization compared with nonprimed controls. Together, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both hepatocyte growth factor and vascular endothelial growth factor. PMID:26798059

Assessment of Growth Factors Secreted by Human Breastmilk Mesenchymal Stem Cells.

PubMed

Kaingade, Pankaj Mahipatrao; Somasundaram, Indumathi; Nikam, Amar Babaso; Sarang, Shabari Amit; Patel, Jagdish Shantilal

2016-01-01

Human breastmilk is a dynamic, multifaceted biological fluid containing nutrients, bioactive substances, and growth factors. It is effective in supporting growth and development of an infant. As breastmilk has been found to possess mesenchymal stem cells, the importance of the components of breastmilk and their physiological roles is increasing day by day. The present study was intended to identify the secretions of growth factors, mainly vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), from human breastmilk mesenchymal stem cells under basal conditions of in vitro cell culture using synthetic media and human cord serum. The growth factors were analyzed with the enzyme-linked immunosorbent assay technique. The cultured mesenchymal stem cells of breastmilk without serum revealed significant differences in secretions of the VEGF and HGF growth factors (8.55 ± 2.26402 pg/mL and 230.8 ± 45.9861 pg/mL, respectively) compared with mesenchymal stem cells of breastmilk with serum (21.31 ± 4.69 pg/mL and 2,404.42 ± 481.593 pg/mL, respectively). Results obtained from our study demonstrate that both VEGF and HGF are secreted in vitro by human breastmilk mesenchymal stem cells. The roles of VEGF and HGF in surfactant secretion, pulmonary maturation, and neonatal maturity have been well established. Thus, we emphasize that breastmilk-derived MSCs could be a potent therapeutic source in treating neonatal diseases. Besides, due to its immense potency, the study also emphasizes the importance of breastfeeding, which is promoted by organizations like the World Heatlh Organization and UNICEF.

Controlled and reversible induction of differentiation and activation of adult human hepatocytes by a biphasic culture technique

PubMed Central

Auth, Marcus K.H.; Boost, Kim A.; Leckel, Kerstin; Beecken, Wolf-Dietrich; Engl, Tobias; Jonas, Dietger; Oppermann, Elsie; Hilgard, Philip; Markus, Bernd H.; Bechstein, Wolf-Otto; Blaheta, Roman A.

2005-01-01

AIM: Clinical application of human hepatocytes (HC) is hampered by the progressive loss of growth and differentiation in vitro. The object of the study was to evaluate the effect of a biphasic culture technique on expression and activation of growth factor receptors and differentiation of human adult HC. METHODS: Isolated HC were sequentially cultured in a hormone enriched differentiation medium (DM) containing nicotinamide, insulin, transferrin, selenium, and dexame-thasone or activation medium (AM) containing hepatocyte growth factor (HGF), epidermal growth factor (EGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Expression, distribution and activation of the HC receptors (MET and EGFR) and the pattern of characteristic cytokeratin (CK) filaments were measured by fluorometry, confocal microscopy and Western blotting. RESULTS: In the biphasic culture system, HC underwent repeated cycles of activation (characterized by expression and activation of growth factor receptors) and re-differentiation (illustrated by distribution of typical filaments CK-18 but low or absent expression of CK-19). In AM increased expression of MET and EGFR was associated with receptor translocation into the cytoplasm and induction of atypical CK-19. In DM low expression of MET and EGFR was localized on the cell membrane and CK-19 was reduced. Receptor phosphorylation required embedding of HC in collagen type I gel. CONCLUSION: Control and reversible modulation of growth factor receptor activation of mature human HC can be accomplished in vitro, when defined signals from the extracellular matrix and sequential growth stimuli are provided. The biphasic technique helps overcome de-differentiation, which occurs during continuous stimulation by means of growth factors. PMID:15810072

Controlled and reversible induction of differentiation and activation of adult human hepatocytes by a biphasic culture technique.

PubMed

Auth, Marcus-K H; Boost, Kim A; Leckel, Kerstin; Beecken, Wolf-Dietrich; Engl, Tobias; Jonas, Dietger; Oppermann, Elsie; Hilgard, Philip; Markus, Bernd H; Bechstein, Wolf-Otto; Blaheta, Roman A

2005-04-14

Clinical application of human hepatocytes (HC) is hampered by the progressive loss of growth and differentiation in vitro. The object of the study was to evaluate the effect of a biphasic culture technique on expression and activation of growth factor receptors and differentiation of human adult HC. Isolated HC were sequentially cultured in a hormone enriched differentiation medium (DM) containing nicotinamide, insulin, transferrin, selenium, and dexame-thasone or activation medium (AM) containing hepatocyte growth factor (HGF), epidermal growth factor (EGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Expression, distribution and activation of the HC receptors (MET and EGFR) and the pattern of characteristic cytokeratin (CK) filaments were measured by fluorometry, confocal microscopy and Western blotting. In the biphasic culture system, HC underwent repeated cycles of activation (characterized by expression and activation of growth factor receptors) and re-differentiation (illustrated by distribution of typical filaments CK-18 but low or absent expression of CK-19). In AM increased expression of MET and EGFR was associated with receptor translocation into the cytoplasm and induction of atypical CK-19. In DM low expression of MET and EGFR was localized on the cell membrane and CK-19 was reduced. Receptor phosphorylation required embedding of HC in collagen type I gel. Control and reversible modulation of growth factor receptor activation of mature human HC can be accomplished in vitro, when defined signals from the extracellular matrix and sequential growth stimuli are provided. The biphasic technique helps overcome de-differentiation, which occurs during continuous stimulation by means of growth factors.

Characteristics of MIC-1 antlerogenic stem cells and their effect on hair growth in rabbits.

PubMed

Cegielski, Marek; Izykowska, Ilona; Chmielewska, Magdalena; Dziewiszek, Wojciech; Bochnia, Marek; Calkosinski, Ireneusz; Dziegiel, Piotr

2013-01-01

We characterized growth factors produced by MIC-1 antlerogenic stem cells and attempted to apply those cells to stimulate hair growth in rabbits. We evaluated the gene and protein expression of growth factors by immunocytochemical and molecular biology techniques in MIC-1 cells. An animal model was used to assess the effects of xenogenous stem cells on hair growth. In the experimental group, rabbits were intradermally injected with MIC-1 stem cells, whereas the control group rabbits were given vehicle-only. After 1, 2 and 4 weeks, skin specimen were collected for histological and immunohistochemical tests. MIC-1 antlerogenic stem cells express growth factors, as confirmed at the mRNA and protein levels. Histological and immunohistochemical analysis demonstrated an increase in the number of hair follicles, as well as the amount of secondary hair in the follicles, without an immune response in animals injected intradermally with MIC-1 cells, compared to animals receiving vehicle-alone. MIC-1 cells accelerated hair growth in rabbits due to the activation of cells responsible for the regulation of the hair growth cycle through growth factors. Additionally, the xenogenous cell implant did not induce immune response.

Neurobiological markers of exercise-related brain plasticity in older adults

PubMed Central

Voss, Michelle W.; Erickson, Kirk I.; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S.; Alves, Heloisa; Szabo, Amanda; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L.; Olson, Erin A.; Gothe, Neha; Potter, Vicki V.; Martin, Stephen A.; Pence, Brandt D.; Cook, Marc D.; Woods, Jeffrey A.; McAuley, Edward; Kramer, Arthur F.

2012-01-01

The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age = 66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF. PMID:23123199

Binding efficiency of recombinant collagen-binding basic fibroblast growth factors (CBD-bFGFs) and their promotion for NIH-3T3 cell proliferation.

PubMed

Wu, Zhenxu; Zhou, Yulai; Chen, Li; Hu, Mingxin; Wang, Yu; Li, Linlong; Wang, Zongliang; Zhang, Peibiao

2018-03-01

The recombinant basic fibroblast growth factor (bFGF) containing collagen-binding domain (CBD) has been found to be a potential therapeutic factor in tissue regeneration. However, its binding efficiency and quantification remain uncertain. In this research, massive recombinant bFGFs with good bioactivity for enhancing the proliferation of NIH-3T3 cells were achieved. An ELISA-based quantitative method was set up to investigate the binding efficiency of CBD-bFGFs on collagen films. It indicated that the CBDs significantly increased the collagen-binding ability of bFGF (P < .05), with the optimum binding condition first determined to be in the pH range of 7.5-9.5 (P < .05). Then, the relevant equations to calculate the binding density of bFGF, C-bFGF, and V-bFGF were acquired. Analysis confirmed that the bioactivity of immobilized bFGFs was well correlated with the density of growth factor on collagen films. Based on this research, the density of growth factor is a logical and applicable dosage unit for quantification of binding efficiency of growth factors, rather than traditional concentration of soluble growth factors in tissue engineering applications. © 2018 Wiley Periodicals, Inc.

Using minimalist self-assembling peptides as hierarchical scaffolds to stabilise growth factors and promote stem cell integration in the injured brain.

PubMed

Rodriguez, A L; Bruggeman, K F; Wang, Y; Wang, T Y; Williams, R J; Parish, C L; Nisbet, D R

2018-03-01

Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue-specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor, up to 172 hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1 hr. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared with cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells. Copyright © 2017 John Wiley & Sons, Ltd.

c-erbA and v-erbA modulate growth and gene expression of a mouse glial precursor cell line.

PubMed

Iglesias, T; Llanos, S; López-Barahona, M; Pérez-Aranda, A; Rodríguez-Peña, A; Bernal, J; Höhne, A; Seliger, B; Muñoz, A

1994-07-01

The c-erbA alpha protooncogene coding for the thyroid hormone (T3) receptor (TR alpha 1) and the viral, mutated v-erbA oncogene were expressed in an immortal mouse glial cell line (B3.1) using retroviral vectors. c-erbA alpha expression led to a decrease in cell proliferation in high and low serum conditions, both in the presence and in the absence of T3. In serum-free medium, c-erbA-expressing cells (B3.1 + TR alpha 1) were completely arrested, whereas cells expressing v-erbA (B3.1 + v-erbA) showed a higher DNA synthesis rate than normal B3.1 cells. Although proliferation of all three cell types was stimulated by platelet-derived growth factor and basic fibroblast growth factor, differences were also observed in the response to these agents. B3.1 + TR alpha 1 cells were more sensitive to platelet-derived growth factor than B3.1 and B3.1 + v-erbA cells. In contrast, B3.1 cells responded to basic fibroblast growth factor better than B3.1 + TR alpha 1 or B3.1 + v-erbA cells. Insulin-like growth factor I potentiated the action of platelet-derived growth factor and basic fibroblast growth factor. Again, different responses to treatment with insulin-like growth factor I alone were observed; B3.1 + TR alpha 1 cells did not respond to it, whereas B3.1 + v-erbA cells showed a dramatic stimulation by this agent. Interestingly, in the presence of T3, the blockade in B3.1 + TR alpha 1 cell proliferation was accompanied by the down-regulation of the typical astrocytic genes, glial fibrillary acidic protein and vimentin. These hormone effects were not found in v-erbA-expressing cells. In addition, v-erbA inhibited the basal expression of the cyclic nucleotide phosphodiesterase gene, an oligodendrocytic marker.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro differentiation of embryonic stem cells into hepatocytes induced by fibroblast growth factors and bone morphological protein-4.

PubMed

Zhou, Qing-Jun; Huang, Yan-Dan; Xiang, Li-Xin; Shao, Jian-Zhong; Zhou, Guo-Shun; Yao, Hang; Dai, Li-Cheng; Lu, Yong-Liang

2007-01-01

The feasibility of transforming embryonic endoderm into different cell types is tightly controlled by mesodermal and septum transversumal signalings during early embryonic development. Here, an induction protocol tracing embryonic liver development was designed, in which, three growth factors, acid fibroblast growth factor, basic fibroblast growth factor and bone morphological protein-4 that secreted from pre-cardiac mesoderm and septum transversum mesenchyme, respectively, were employed to investigate their specific potency of modulating the mature hepatocyte proportion during the differentiation process. Results showed that hepatic differentiation took place spontaneously at a low level, however, supplements of the three growth factors gave rise to a significant up-regulation of mature hepatocytes. Bone morphological protein-4 highlighted the differentiation ratio to 40-55%, showing the most effective promotion, and also exhibited a synergistic effect with the other two fibroblast factors, whereas no similar phenomenon was observed between the other two factors, which was reported for the first time. Our study not only provides a high-performance system of embryonic stem cells differentiating into hepatocytes, which would supply a sufficient hepatic population for related studies, but also make it clear of the inductive effects of three important growth factors, which could support for further investigation on the mechanisms of mesodermal and septumal derived signalings that regulate hepatic differentiation.

Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: role of growth factors in normal and pathological wound healing: therapeutic potential and methods of delivery.

PubMed

Demidova-Rice, Tatiana N; Hamblin, Michael R; Herman, Ira M

2012-08-01

This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed.

Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 2: Role of Growth Factors in Normal and Pathological Wound Healing: Therapeutic Potential and Methods of Delivery

PubMed Central

Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.

2012-01-01

This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. PMID:22820962

Expression of Inappropriate Cadherins in Human Breast Carcinomas

DTIC Science & Technology

2000-10-01

fibroblast growth factor receptor ADHERINS constitute a family of transmembrane Hamaguchi et al., 1993). In addition, p120ct", originally...1994. expression is associated with poor prognosis in patients with prostate cancer. Alternative splicing in fibroblast growth factor receptor 2 is... fibroblast growth factor receptor signaling. This year we report that the extracellular domain of N-cadherin is responsible for this

Identification of growth phases and influencing factors in cultivations with AGE1.HN cells using set-based methods.

PubMed

Borchers, Steffen; Freund, Susann; Rath, Alexander; Streif, Stefan; Reichl, Udo; Findeisen, Rolf

2013-01-01

Production of bio-pharmaceuticals in cell culture, such as mammalian cells, is challenging. Mathematical models can provide support to the analysis, optimization, and the operation of production processes. In particular, unstructured models are suited for these purposes, since they can be tailored to particular process conditions. To this end, growth phases and the most relevant factors influencing cell growth and product formation have to be identified. Due to noisy and erroneous experimental data, unknown kinetic parameters, and the large number of combinations of influencing factors, currently there are only limited structured approaches to tackle these issues. We outline a structured set-based approach to identify different growth phases and the factors influencing cell growth and metabolism. To this end, measurement uncertainties are taken explicitly into account to bound the time-dependent specific growth rate based on the observed increase of the cell concentration. Based on the bounds on the specific growth rate, we can identify qualitatively different growth phases and (in-)validate hypotheses on the factors influencing cell growth and metabolism. We apply the approach to a mammalian suspension cell line (AGE1.HN). We show that growth in batch culture can be divided into two main growth phases. The initial phase is characterized by exponential growth dynamics, which can be described consistently by a relatively simple unstructured and segregated model. The subsequent phase is characterized by a decrease in the specific growth rate, which, as shown, results from substrate limitation and the pH of the medium. An extended model is provided which describes the observed dynamics of cell growth and main metabolites, and the corresponding kinetic parameters as well as their confidence intervals are estimated. The study is complemented by an uncertainty and outlier analysis. Overall, we demonstrate utility of set-based methods for analyzing cell growth and metabolism under conditions of uncertainty.

Identification of Growth Phases and Influencing Factors in Cultivations with AGE1.HN Cells Using Set-Based Methods

PubMed Central

Borchers, Steffen; Freund, Susann; Rath, Alexander; Streif, Stefan; Reichl, Udo; Findeisen, Rolf

2013-01-01

Production of bio-pharmaceuticals in cell culture, such as mammalian cells, is challenging. Mathematical models can provide support to the analysis, optimization, and the operation of production processes. In particular, unstructured models are suited for these purposes, since they can be tailored to particular process conditions. To this end, growth phases and the most relevant factors influencing cell growth and product formation have to be identified. Due to noisy and erroneous experimental data, unknown kinetic parameters, and the large number of combinations of influencing factors, currently there are only limited structured approaches to tackle these issues. We outline a structured set-based approach to identify different growth phases and the factors influencing cell growth and metabolism. To this end, measurement uncertainties are taken explicitly into account to bound the time-dependent specific growth rate based on the observed increase of the cell concentration. Based on the bounds on the specific growth rate, we can identify qualitatively different growth phases and (in-)validate hypotheses on the factors influencing cell growth and metabolism. We apply the approach to a mammalian suspension cell line (AGE1.HN). We show that growth in batch culture can be divided into two main growth phases. The initial phase is characterized by exponential growth dynamics, which can be described consistently by a relatively simple unstructured and segregated model. The subsequent phase is characterized by a decrease in the specific growth rate, which, as shown, results from substrate limitation and the pH of the medium. An extended model is provided which describes the observed dynamics of cell growth and main metabolites, and the corresponding kinetic parameters as well as their confidence intervals are estimated. The study is complemented by an uncertainty and outlier analysis. Overall, we demonstrate utility of set-based methods for analyzing cell growth and metabolism under conditions of uncertainty. PMID:23936299

Modeling Vascularized Bone Regeneration Within a Porous Biodegradable CaP Scaffold Loaded with Growth Factors

PubMed Central

Sun, X; Kang, Y; Bao, J; Zhang, Y; Yang, Y; Zhou, X

2013-01-01

Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors. PMID:23566802

L-ascorbic acid 2-phosphate and fibroblast growth factor-2 treatment maintains differentiation potential in bone marrow-derived mesenchymal stem cells through expression of hepatocyte growth factor.

PubMed

Bae, Sung Hae; Ryu, Hoon; Rhee, Ki-Jong; Oh, Ji-Eun; Baik, Soon Koo; Shim, Kwang Yong; Kong, Jee Hyun; Hyun, Shin Young; Pack, Hyun Sung; Im, Changjo; Shin, Ha Cheol; Kim, Yong Man; Kim, Hyun Soo; Eom, Young Woo; Lee, Jong In

2015-04-01

l-ascorbic acid 2-phosphate (Asc-2P) acts as an antioxidant and a stimulator of hepatocyte growth factor (HGF) production. Previously, we reported that depletion of growth factors such as fibroblast growth factor (FGF)-2, epidermal growth factor (EGF), FGF-4 and HGF during serial passage could induce autophagy, senescence and down-regulation of stemness (proliferation via FGF-2/-4 and differentiation via HGF). In this study, we investigated the proliferation and differentiation potential of BMSCs by FGF-2 and Asc-2P. Co-treatment with FGF-2 and Asc-2P induced optimal proliferation of BMSCs and increased the accumulation rate of BMSC numbers during a 2-month culture period. Moreover, differentiation potential was maintained by co-treatment with FGF-2 and Asc-2P via HGF expression. Adipogenic differentiation potential by FGF-2 and Asc-2P was dramatically suppressed by c-Met inhibitors (SU11274). These data suggest that co-treatment with FGF-2 and Asc-2P would be beneficial in obtaining BMSCs that possess "stemness" during long-term culture.

Basic fibroblast growth factor (bFGF) facilitates differentiation of adult dorsal root ganglia-derived neural stem cells toward Schwann cells by binding to FGFR-1 through MAPK/ERK activation.

PubMed

Gu, Yun; Xue, Chenbin; Zhu, Jianbin; Sun, Hualin; Ding, Fei; Cao, Zheng; Gu, Xiaosong

2014-04-01

Considerable research has been devoted to unraveling the regulation of neural stem cell (NSC) differentiation. The responses of NSCs to various differentiation-inducing stimuli, however, are still difficult to estimate. In this study, we aimed to search for a potent growth factor that was able to effectively induce differentiation of NSCs toward Schwann cells. NSCs were isolated from dorsal root ganglia (DRGs) of adult rats and identified by immunostaining. Three different growth factors were used to stimulate the differentiation of DRG-derived NSCs (DRG-NSCs). We found that among these three growth factors, bFGF was the strongest inducer for the glial differentiation of DRG-NSCs, and bFGF induced the generation of an increased number of Schwann cell-like cells as compared to nerve growth factor (NGF) and neuregulin1-β (NRG). These Schwann cell-like cells demonstrated the same characteristics as those of primary Schwann cells. Furthermore, we noted that bFGF-induced differentiation of DRG-NSCs toward Schwann cells might be mediated by binding to fibroblast growth factor receptor-1 (FGFR-1) through activation of MAPK/ERK signal pathway.

Insulin-like growth factor-I and growth differentiation factor-5 promote the formation of tissue-engineered human nasal septal cartilage.

PubMed

Alexander, Thomas H; Sage, August B; Chen, Albert C; Schumacher, Barbara L; Shelton, Elliot; Masuda, Koichi; Sah, Robert L; Watson, Deborah

2010-10-01

Tissue engineering of human nasal septal chondrocytes offers the potential to create large quantities of autologous material for use in reconstructive surgery of the head and neck. Culture with recombinant human growth factors may improve the biochemical and biomechanical properties of engineered tissue. The objectives of this study were to (1) perform a high-throughput screen to assess multiple combinations of growth factors and (2) perform more detailed testing of candidates identified in part I. In part I, human nasal septal chondrocytes from three donors were expanded in monolayer with pooled human serum (HS). Cells were then embedded in alginate beads for 2 weeks of culture in medium supplemented with 2% or 10% HS and 1 of 90 different growth factor combinations. Combinations of insulin-like growth factor-I (IGF-1), bone morphogenetic protein (BMP)-2, BMP-7, BMP-13, growth differentiation factor-5 (GDF-5), transforming growth factor β (TGFβ)-2, insulin, and dexamethasone were evaluated. Glycosaminoglycan (GAG) accumulation was measured. A combination of IGF-1 and GDF-5 was selected for further testing based on the results of part I. Chondrocytes from four donors underwent expansion followed by three-dimensional alginate culture for 2 weeks in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5. Chondrocytes and their associated matrix were then recovered and cultured for 4 weeks in 12 mm transwells in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5 (the same medium used for alginate culture). Biochemical and biomechanical properties of the neocartilage were measured. In part I, GAG accumulation was highest for growth factor combinations including both IGF-1 and GDF-5. In part II, the addition of IGF-1 and GDF-5 to 2% HS resulted in a 12-fold increase in construct thickness compared with 2% HS alone (p < 0.0001). GAG and type II collagen accumulation was significantly higher with IGF-1 and GDF-5. Confined compression modulus was greatest with 2% HS, IGF-1, and GDF-5. Supplementation of medium with IGF-1 and GDF-5 during creation of neocartilage constructs results in increased accumulation of GAG and type II collagen and improved biomechanical properties compared with constructs created without the growth factors.

E2F1 transcription factor and its impact on growth factor and cytokine signaling.

PubMed

Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

2016-10-01

E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ). Copyright © 2016 Elsevier Ltd. All rights reserved.

Canine splenic haemangiosarcoma: influence of metastases, chemotherapy and growth pattern on post-splenectomy survival and expression of angiogenic factors.

PubMed

Göritz, M; Müller, K; Krastel, D; Staudacher, G; Schmidt, P; Kühn, M; Nickel, R; Schoon, H-A

2013-07-01

Splenic haemangiosarcomas (HSAs) from 122 dogs were characterized and classified according to their patterns of growth, survival time post splenectomy, metastases and chemotherapy. The most common pattern of growth was a mixture of cavernous, capillary and solid tumour tissue. Survival time post splenectomy was independent of the growth pattern; however, it was influenced by chemotherapy and metastases. Immunohistochemical assessment of the expression of angiogenic factors (fetal liver kinase-1, angiopoietin-2, angiopoietin receptor-2 and vascular endothelial growth factor A) and conventional endothelial markers (CD31, factor VIII-related antigen) revealed variable expression, particularly in undifferentiated HSAs. Therefore, a combination of endothelial markers should be used to confirm the endothelial origin of splenic tumours. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regulation of rat mesangial cell growth by diadenosine phosphates.

PubMed Central

Heidenreich, S; Tepel, M; Schlüter, H; Harrach, B; Zidek, W

1995-01-01

The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC). Both AP5A and AP6A stimulated growth in micromolar concentrations. The growth stimulatory effect exceeded that of ATP, alpha,beta-methylene ATP, adenosine 5'-O-(3-thio)triphosphate and UTP. Both diadenosine phosphates potentiated the growth response to platelet-derived growth factor, but not to insulin-like growth factor-1. To further elucidate the site of action in the cell cycle, RNA and protein synthesis were assessed. AP5 and AP6A stimulated protein synthesis, but not RNA formation. Furthermore, both agents increased cytosolic free Ca2+ concentration. It is concluded that AP5A and AP6A may play a regulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease. PMID:7769127

Platelet lysate obtained via plateletpheresis performed in standing and awake equine donors.

PubMed

Sumner, Scarlett M; Naskou, Maria C; Thoresen, Merrilee; Copland, Ian; Peroni, John F

2017-07-01

Platelet preparations containing growth factors, attachment factors, and enzymes are appealing to enhance healing of injured tissues and as an alternative to xenogenic serum in cell culture media. Plateletpheresis is commonly used to collect platelets in human medicine but has not been validated in horses. Plateletpheresis to collect platelet concentrate was performed on six female, mixed breed, chemically restrained horses using commercially available apheresis equipment. Before and immediately after plateletpheresis, we performed physical examinations and collected blood for chemistry and coagulation panels and then again at 8, 16, 24, and 48 hours after the procedure. To produce platelet lysate, the platelet concentrate underwent two freeze-thaw cycles followed by centrifugation and filtration processing. The platelet lysate was then analyzed for cellular debris, fibrinogen, and growth factors. The collected platelet concentration contained a mean platelet yield of 390 × 10 3 /μL. Donor platelet count decreased from a mean of 193 × 10 3 /μL to 138 × 10 3 /μL after plateletpheresis, but no individual was at risk for hemorrhage. Pooled platelet lysate had minimal cellular residue and contained growth factor concentrations at 6.1 ng/mL for transforming growth factor-β1, at 3.5 ng/mL for platelet-derived growth factor-BB, and at 13.8 ng/mL for vascular endothelial growth factor-A. Plateletpheresis using commercially available apheresis equipment is a feasible option for collecting platelet concentrate from equine donors. The lysate generated from the apheresis product contains growth factors and has potential to be used as a fetal bovine serum substitute for cell culture. © 2017 AABB.

Stomatal and non-stomatal factors regulated the photosynthesis of soybean seedlings in the present of exogenous bisphenol A.

PubMed

Jiao, Liya; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2017-11-01

Bisphenol A (BPA) is an emerging environmental endocrine disruptor that has toxic effects on plants growth. Photosynthesis supplies the substances and energy required for plant growth, and regulated by stomatal and non-stomatal factors. Therefore, in this study, to reveal how BPA affects photosynthesis in soybean seedlings (Glycine max L.) from the perspective of stomatal and non-stomatal factors, the stomatal factors (stomatal conductance and behaviours) and non-stomatal factors (Hill reaction, apparent quantum efficiency, Rubisco activity, carboxylation efficiency, the maximum Rubisco carboxylation velocity, ribulose-1,5-bisphospate regeneration capacities mediated by maximum electron transport rates, and triose phosphate utilization rate) were investigated using a portable photosynthesis system. Moreover, the pollution of BPA in the environment was simulated. The results indicate that low-dose BPA enhanced net photosynthetic rate (P n ) primarily by promoting stomatal factors, resulting in increased relative growth rates and accelerated soybean seedling growth. High-dose BPA decreases the P n by simultaneously inhibiting stomatal and non-stomatal factors, and this inhibition decreases the relative growth rates further reducing soybean seedling growth. Following the withdrawal of BPA, all of the indices were restored to varying degrees. In conclusion, low-dose BPA increased the P n by promoting stomatal factors while high-dose BPA decreased the P n by simultaneously inhibiting stomatal and non-stomatal factors. These findings provide a model (or, hypothesis) for the effects of BPA on plant photosynthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Growth factor involvement in tension-induced skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, H. H.

1987-01-01

Muscle tissue culture techniques were developed to grow skeletal myofibers which differentiate into more adult-like myofibers. Mechanical simulation studies of these muscle cells in a newly developed mechanical cell simulator can now be performed to study growth processes in skeletal muscle. Conditions in the mechanical cell simulator were defined where mechanical activity can either prevent muscle wasting or stimulate muscle growth. The role of endogenous and exogenous growth factors in tension-induced muscle growth is being investigated under the defined conditions of tissue culture.

Combination of three angiogenic growth factors has synergistic effects on sprouting of endothelial cell/mesenchymal stem cell-based spheroids in a 3D matrix.

PubMed

Kim, Sook Kyoung; Lee, Jaeyeon; Song, Myeongjin; Kim, Mirim; Hwang, Soon Jung; Jang, Hwanseok; Park, Yongdoo

2016-11-01

Combinations of angiogenic growth factors have been shown to have synergistic effects on angiogenesis and natural wound healing in various animal models. Each growth factor has unique roles during angiogenesis; vascular endothelial growth factor (VEGF) plays a key role during the initial step of angiogenesis, whereas PDGF functions in the maturation of blood vessels. We used a combination of three angiogenic growth factors to increase angiogenesis in vitro and in vivo. We chose VEGF as a basic factor and added platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) to induce angiogenesis in three in vitro and in vivo models: 3D angiogenesis assay, 3D co-culture, and matrigel plug implantation assay. Cell proliferation was significantly higher in co-cultured cells treated with PDGF + VEGF + FGF than in the control, single, or dual combination groups. mRNA expression of α-smooth muscle actin (α-SMA), von Willebrand factor (vWF), and CD105 was higher in the triple group (PDGF + VEGF + FGF) than in control, single, or dual combination groups. In the PDGF + VEGF + FGF group, the length and number of branches of spheroids was also significantly higher than in the control, single, or dual combination groups. Furthermore, in a nude mouse model, α-SMA expression was significantly higher in the PDGF + VEGF + FGF group than in other groups. In conclusion, the addition of PDGF and FGF to VEGF showed synergistic effects on angiogenesis in vitro and in vivo. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1535-1543, 2016. © 2015 Wiley Periodicals, Inc.

Growth hormone and insulin-like growth factors in fish: Where we are and where to go

USGS Publications Warehouse

Reinecke, M.; Bjornsson, Bjorn Thrandur; Dickhoff, Walton W.; McCormick, S.D.; Navarro, I.; Power, D.M.; Gutierrez, J.

2005-01-01

This communication summarizes viewpoints, discussion, perspectives, and questions, put forward at a workshop on "Growth hormone and insulin-like growth factors in fish" held on September 7th, 2004, at the 5th International Symposium on Fish Endocrinology in Castello??n, Spain. ?? 2005 Elsevier Inc. All rights reserved.

[Investigation of mechanisms of action of growth factors of autologous platelet-rich plasma used to treat erectile dysfunction].

PubMed

Epifanova, M V; Chalyi, M E; Krasnov, A O

2017-09-01

To determine the quantitative and qualitative composition of growth factors (PDGF-AA, PDGF-BB, VEGF, VEGF-D, FGF-acid, FGF-basic) and platelets in various modifications of APRP. Blood of 12 male volunteers (control group) and 12 patients with ED was used to prepare APRP and the subsequently determine the concentration of growth factors. The growth factor concentrations (FGF acid, FGF basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D) was determined using a flow cytometry-based xMAP Luminex (Gen-Probe) system. Concentration of platelets in APRP obtained by two stage centrifugation, reached 1480 (1120-1644) in the control group and 1232 (956-1502) in patients with ED. The concentration of growth factors in the samples prepared without preliminary freezing was: PDGF-AA 842 (22-3700), PDGF-BB 2837 (1460-4100), FGF-basic 7.9 (0.28-127), FGF-acid 3, 4 (0.14-11), VEGF 19 (4.6-46), VEGF-D 21 (14-38). After thawing, the concentration of all growth factors in the samples increased. The study findings suggest that the mechanism of erectile function recovery following the use of APRP is through the active substances detected in APRP, i.e. FGF-basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D and FGF-acid. Also, the study showed that the content of growth factors in APRP after of freezing/thawing is higher than in APRP that has not been frozen. This is due to the cell membrane destruction at extremely low temperatures during freezing.

Basic Fibroblast Growth Factor Influences Epidermal Homeostasis of Living Skin Equivalents through Affecting Fibroblast Phenotypes and Functions.

PubMed

Yang, Lujun; Zhang, Dangui; Wu, Hongjuan; Xie, Sitian; Zhang, Mingjun; Zhang, Bingna; Tang, Shijie

2018-05-30

To elucidate the possible mechanisms of how basic fibroblast growth factor (bFGF) influences epidermal homeostasis in a living skin equivalent (LSE) model. Several wound healing-related growth factors were analyzed at protein and mRNA levels for dermal fibroblasts of induced alpha-smooth muscle actin (α-SMA)-positive or α-SMA-negative phenotypes. During culturing an LSE model by seeding normal human keratinocytes on a fibroblast-populated type I collagen gel, bFGF or neutralizing antibody for keratinocyte growth factor (KGF) was added to investigate its effects on fibroblast phenotypes and, subsequently, epidermal homeostasis by histology and immunohistochemistry. The α-SMA-positive phenotype of fibroblasts induced by transforming growth factor beta-1 (TGF-β1) markedly suppressed the expression of KGF and hepatocyte growth factor (HGF), and slightly upregulated vascular endothelial growth factor (VEGF) and TGF-β1 at mRNA and protein levels, compared with α-SMA-negative fibroblasts treated with bFGF. α-SMA expression of fibroblasts at the epidermal-mesenchymal junction of the LSEs was suppressed by the addition of bFGF, and a better-differentiated epidermis was presented. The abrogation of KGF from fibroblasts by the addition of the KGF neutralizing antibody disenabled the LSE culturing system to develop an epidermis. bFGF, through affecting the phenotypes and functions of fibroblasts, especially KGF expression, influenced epidermal homeostasis in an LSE model. © 2018 S. Karger AG, Basel.

Bioglass Activated Skin Tissue Engineering Constructs for Wound Healing.

PubMed

Yu, Hongfei; Peng, Jinliang; Xu, Yuhong; Chang, Jiang; Li, Haiyan

2016-01-13

Wound healing is a complicated process, and fibroblast is a major cell type that participates in the process. Recent studies have shown that bioglass (BG) can stimulate fibroblasts to secrete a multitude of growth factors that are critical for wound healing. Therefore, we hypothesize that BG can stimulate fibroblasts to have a higher bioactivity by secreting more bioactive growth factors and proteins as compared to untreated fibroblasts, and we aim to construct a bioactive skin tissue engineering graft for wound healing by using BG activated fibroblast sheet. Thus, the effects of BG on fibroblast behaviors were studied, and the bioactive skin tissue engineering grafts containing BG activated fibroblasts were applied to repair the full skin lesions on nude mouse. Results showed that BG stimulated fibroblasts to express some critical growth factors and important proteins including vascular endothelial growth factor, basic fibroblast growth factor, epidermal growth factor, collagen I, and fibronectin. In vivo results revealed that fibroblasts in the bioactive skin tissue engineering grafts migrated into wound bed, and the migration ability of fibroblasts was stimulated by BG. In addition, the bioactive BG activated fibroblast skin tissue engineering grafts could largely increase the blood vessel formation, enhance the production of collagen I, and stimulate the differentiation of fibroblasts into myofibroblasts in the wound site, which would finally accelerate wound healing. This study demonstrates that the BG activated skin tissue engineering grafts contain more critical growth factors and extracellular matrix proteins that are beneficial for wound healing as compared to untreated fibroblast cell sheets.

Extracellular growth factors and mitogens cooperate to drive mitochondrial biogenesis

PubMed Central

Echave, Pedro; Machado-da-Silva, Gisela; Arkell, Rebecca S.; Duchen, Michael R.; Jacobson, Jake; Mitter, Richard; Lloyd, Alison C.

2009-01-01

Summary Cells generate new organelles when stimulated by extracellular factors to grow and divide; however, little is known about how growth and mitogenic signalling pathways regulate organelle biogenesis. Using mitochondria as a model organelle, we have investigated this problem in primary Schwann cells, for which distinct factors act solely as mitogens (neuregulin) or as promoters of cell growth (insulin-like growth factor 1; IGF1). We find that neuregulin and IGF1 act synergistically to increase mitochondrial biogenesis and mitochondrial DNA replication, resulting in increased mitochondrial density in these cells. Moreover, constitutive oncogenic Ras signalling results in a further increase in mitochondrial density. This synergistic effect is seen at the global transcriptional level, requires both the ERK and phosphoinositide 3-kinase (PI3K) signalling pathways and is mediated by the transcription factor ERRα. Interestingly, the effect is independent of Akt-TOR signalling, a major regulator of cell growth in these cells. This separation of the pathways that drive mitochondrial biogenesis and cell growth provides a mechanism for the modulation of mitochondrial density according to the metabolic requirements of the cell. PMID:19920079

Stromal Cells Positively and Negatively Modulate the Growth of Cancer Cells: Stimulation via the PGE2-TNFα-IL-6 Pathway and Inhibition via Secreted GAPDH-E-Cadherin Interaction

PubMed Central

Kawada, Manabu; Inoue, Hiroyuki; Ohba, Shun-ichi; Yoshida, Junjiro; Masuda, Tohru; Yamasaki, Manabu; Usami, Ihomi; Sakamoto, Shuichi; Abe, Hikaru; Watanabe, Takumi; Yamori, Takao; Shibasaki, Masakatsu; Nomoto, Akio

2015-01-01

Fibroblast-like stromal cells modulate cancer cells through secreted factors and adhesion, but those factors are not fully understood. Here, we have identified critical stromal factors that modulate cancer growth positively and negatively. Using a cell co-culture system, we found that gastric stromal cells secreted IL-6 as a growth and survival factor for gastric cancer cells. Moreover, gastric cancer cells secreted PGE2 and TNFα that stimulated IL-6 secretion by the stromal cells. Furthermore, we found that stromal cells secreted glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Extracellular GAPDH, or its N-terminal domain, inhibited gastric cancer cell growth, a finding confirmed in other cell systems. GAPDH bound to E-cadherin and downregulated the mTOR-p70S6 kinase pathway. These results demonstrate that stromal cells could regulate cancer cell growth through the balance of these secreted factors. We propose that negative regulation of cancer growth using GAPDH could be a new anti-cancer strategy. PMID:25785838

Gene therapy with growth factors for periodontal tissue engineering–A review

PubMed Central

Gupta, Shipra; Mahendra, Aneet

2012-01-01

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

Characterization of the growth of murine fibroblasts that express human insulin receptors. II. Interaction of insulin with other growth factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randazzo, P.A.; Jarett, L.

1990-09-01

The effects of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin on DNA synthesis were studied in murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental NIH 3T3 cells. In NIH 3T3/HIR cells, individual growth factors in serum-free medium stimulated DNA synthesis with the following relative efficacies: insulin greater than or equal to 10% fetal calf serum greater than PDGF greater than IGF-1 much greater than EGF. In comparison, the relative efficacies of these factors in stimulating DNA synthesis by NIH 3T3 cells were 10% fetalmore » calf serum greater than PDGF greater than EGF much greater than IGF-1 = insulin. In NIH 3T3/HIR cells, EGF was synergistic with 1-10 ng/ml insulin but not with 100 ng/ml insulin or more. Synergy of PDGF or IGF-1 with insulin was not detected. In the parental NIH 3T3 cells, insulin and IGF-1 were found to be synergistic with EGF (1 ng/ml), PDGF (100 ng/ml), and PDGF plus EGF. In NIH 3T3/HIR cells, the lack of interaction of insulin with other growth factors was also observed when the percentage of cells synthesizing DNA was examined. Despite insulin's inducing only 60% of NIH 3T3/HIR cells to incorporate thymidine, addition of PDGF, EGF, or PDGF plus EGF had no further effect. In contrast, combinations of growth factors resulted in 95% of the parental NIH 3T3 cells synthesizing DNA. The independence of insulin-stimulated DNA synthesis from other mitogens in the NIH 3T3/HIR cells is atypical for progression factor-stimulated DNA synthesis and is thought to be partly the result of insulin receptor expression in an inappropriate context or quantity.« less

Identifying ontogenetic, environmental and individual components of forest tree growth

PubMed Central

Chaubert-Pereira, Florence; Caraglio, Yves; Lavergne, Christian; Guédon, Yann

2009-01-01

Background and Aims This study aimed to identify and characterize the ontogenetic, environmental and individual components of forest tree growth. In the proposed approach, the tree growth data typically correspond to the retrospective measurement of annual shoot characteristics (e.g. length) along the trunk. Methods Dedicated statistical models (semi-Markov switching linear mixed models) were applied to data sets of Corsican pine and sessile oak. In the semi-Markov switching linear mixed models estimated from these data sets, the underlying semi-Markov chain represents both the succession of growth phases and their lengths, while the linear mixed models represent both the influence of climatic factors and the inter-individual heterogeneity within each growth phase. Key Results On the basis of these integrative statistical models, it is shown that growth phases are not only defined by average growth level but also by growth fluctuation amplitudes in response to climatic factors and inter-individual heterogeneity and that the individual tree status within the population may change between phases. Species plasticity affected the response to climatic factors while tree origin, sampling strategy and silvicultural interventions impacted inter-individual heterogeneity. Conclusions The transposition of the proposed integrative statistical modelling approach to cambial growth in relation to climatic factors and the study of the relationship between apical growth and cambial growth constitute the next steps in this research. PMID:19684021

Melasma treatment: A novel approach using a topical agent that contains an anti-estrogen and a vascular endothelial growth factor inhibitor.

PubMed

Cohen, Philip R

2017-04-01

Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors including female sex hormones, genetic predisposition and ultraviolet light exposure. The management of melasma is usually directed at more than one of the causative etiologic factors and often incorporates a combination of topical agents, with or without the addition of physical modalities. Estrogen and angiogenesis are significant factors in the etiology of melasma. A useful addition to the therapeutic armentarium for treating melasma would include a topical agent that could effect both of these causative factors. Specifically, a topical preparation consisting of an anti-estrogen and a vascular endothelial growth factor inhibitor would accomplish this goal. Suitable candidates that target estrogen receptors and vascular endothelial growth factor are currently used in medical oncology as systemic antineoplastic agents. The anti-estrogen could be either a selective estrogen receptor modulator (such as tamoxifen or raloxifene) or an aromatase inhibitor (such as anastrozole or letrozole or exemestane). The vascular endothelial growth factor inhibitor would be bevacizumab. In conclusion, a novel-topically administered-therapy for melasma would combine an anti-estrogen and a vascular endothelial growth factor inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of leukemia inhibitory factor and basic fibroblast growth factor on free radicals and endogenous stem cell proliferation in a mouse model of cerebral infarction.

PubMed

Huang, Weihui; Li, Yadan; Lin, Yufeng; Ye, Xue; Zang, Dawei

2012-07-05

The present study established a mouse model of cerebral infarction by middle cerebral artery occlusion, and monitored the effect of 25 μg/kg leukemia inhibitory factor and (or) basic fibroblast growth factor administration 2 hours after model establishment. Results showed that following administration, the number of endogenous neural stem cells in the infarct area significantly increased, malondialdehyde content in brain tissue homogenates significantly decreased, nitric oxide content, glutathione peroxidase and superoxide dismutase activity significantly elevated, and mouse motor function significantly improved as confirmed by the rotarod and bar grab tests. In particular, the effect of leukemia inhibitory factor in combination with basic fibroblast growth factor was the most significant. Results indicate that leukemia inhibitory factor and basic fibroblast growth factor can improve the microenvironment after cerebral infarction by altering free radical levels, improving the quantity of endogenous neural stem cells, and promoting neurological function of mice with cerebral infarction.

Effects of inhalational anaesthetics in experimental allergic asthma.

PubMed

Burburan, S M; Silva, J D; Abreu, S C; Samary, C S; Guimarães, I H L; Xisto, D G; Morales, M M; Rocco, P R M

2014-06-01

We evaluated whether isoflurane, halothane and sevoflurane attenuate the inflammatory response and improve lung morphofunction in experimental asthma. Fifty-six BALB/c mice were sensitised and challenged with ovalbumin and anaesthetised with isoflurane, halothane, sevoflurane or pentobarbital sodium for one hour. Lung mechanics and histology were evaluated. Gene expression of pro-inflammatory (tumour necrosis factor-α), pro-fibrogenic (transforming growth factor-β) and pro-angiogenic (vascular endothelial growth factor) mediators, as well as oxidative process modulators, were analysed. These modulators included nuclear factor erythroid-2 related factor 2, sirtuin, catalase and glutathione peroxidase. Isoflurane, halothane and sevoflurane reduced airway resistance, static lung elastance and atelectasis when compared with pentobarbital sodium. Sevoflurane minimised bronchoconstriction and cell infiltration, and decreased tumour necrosis factor-α, transforming growth factor-β, vascular endothelial growth factor, sirtuin, catalase and glutathione peroxidase, while increasing nuclear factor erythroid-2-related factor 2 expression. Sevoflurane down-regulated inflammatory, fibrogenic and angiogenic mediators, and modulated oxidant-antioxidant imbalance, improving lung function in this model of asthma. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways.

PubMed

Huh, Jeong-Eun; Nam, Dong-Woo; Baek, Young-Hyun; Kang, Jung Won; Park, Dong-Suk; Choi, Do-Young; Lee, Jae-Dong

2011-01-01

Formononetin, a phytoestrogen from the root of Astragalus membranaceus, is used as a blood enhancer and to improve blood microcirculation in complementary and alternative medicine. The present study investigated the influence of formononetin on the expression of early growth response factor-1 (Egr-1) and growth factors contributing to wound healing. Formononetin significantly increased growth factors such as transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells (HUVECs). Formononetin also increased the expression of Egr-1 transcription factor by 3.2- and 10.5-fold, compared with recombinant VEGF(125) in HUVECs. The formononetin-mediated 12%-43% increase induced endothelial cell proliferation and recovered the migration of wounded HUVECs. In an ex vivo angiogenesis assay, formononetin produced a larger capillary sprouting area than produced using recombinant VEGF(125). Cell proliferation and migration of HUVECs were also greater in the presence of formonectin than VEGF(125). Western blot analysis of scratch-wounded confluent HUVECs showed that formononetin induced the phosphorylation of extracellular signal-regulated kinase (ERK) and slightly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The formononetin-mediated sustained activation of Egr-1 was suppressed by the ERK inhibitor PD98059 and the p38 inhibitor SB203580. PD98059 inhibited the formononetin-induced endothelial proliferation and repair in scratch-wounded HUVECs, SB203580 increased the cell proliferation and wound healing. Formononetin accelerate wound closure rate as early as day 3 after surgery and consistently observed until day 10 after in wound animal model. These data suggest that formononetin promotes endothelial repair and wound healing in a process involving the over-expression of Egr-1 transcription factor through the regulation of the ERK1/2 and p38 MAPK pathways. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh

PubMed Central

Gernand, Alison D.; Schulze, Kerry J.; Nanayakkara-Bind, Ashika; Arguello, Margia; Shamim, Abu Ahmed; Ali, Hasmot; Wu, Lee; West, Keith P.; Christian, Parul

2015-01-01

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies. Trial Registration ClinicalTrials.gov NCT00860470 PMID:26431336

Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh.

PubMed

Gernand, Alison D; Schulze, Kerry J; Nanayakkara-Bind, Ashika; Arguello, Margia; Shamim, Abu Ahmed; Ali, Hasmot; Wu, Lee; West, Keith P; Christian, Parul

2015-01-01

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies. ClinicalTrials.gov NCT00860470.

Control of Human Endometrial Stromal Cell Motility by PDGF-BB, HB-EGF and Trophoblast-Secreted Factors

PubMed Central

Schwenke, Maren; Knöfler, Martin; Velicky, Philipp; Weimar, Charlotte H. E.; Kruse, Michelle; Samalecos, Annemarie; Wolf, Anja; Macklon, Nick S.; Bamberger, Ana-Maria; Gellersen, Birgit

2013-01-01

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site. PMID:23349855

Deficiency of the protein-tyrosine phosphatase DEP-1/PTPRJ promotes matrix metalloproteinase-9 expression in meningioma cells.

PubMed

Petermann, Astrid; Stampnik, Yvonn; Cui, Yan; Morrison, Helen; Pachow, Doreen; Kliese, Nadine; Mawrin, Christian; Böhmer, Frank-D

2015-05-01

Brain-invasive growth of a subset of meningiomas is associated with less favorable prognosis. The molecular mechanisms causing invasiveness are only partially understood, however, the expression of matrix metalloproteinases (MMPs) has been identified as a contributing factor. We have previously found that loss of density enhanced phosphatase-1 (DEP-1, also designated PTPRJ), a transmembrane protein-tyrosine phosphatase, promotes meningioma cell motility and invasive growth in an orthotopic xenotransplantation model. We have now analyzed potential alterations of the expression of genes involved in motility control, caused by DEP-1 loss in meningioma cell lines. DEP-1 depleted cells exhibited increased expression of mRNA encoding MMP-9, and the growth factors EGF and FGF-2. The increase of MMP-9 expression in DEP-1 depleted cells was also readily detectable at the protein level by zymography. MMP-9 upregulation was sensitive to chemical inhibitors of growth factor signal transduction. Conversely, MMP-9 mRNA levels could be stimulated with growth factors (e.g. EGF) and inflammatory cytokines (e.g. TNFα). Increase of MMP-9 expression by DEP-1 depletion, or growth factor/cytokine stimulation qualitatively correlated with increased invasiveness in vitro scored as transmigration through matrigel-coated membranes. The studies suggest induction of MMP-9 expression promoted by DEP-1 deficiency, or potentially by growth factors and inflammatory cytokines, as a mechanism contributing to meningioma brain invasiveness.

Controllable mineral coatings on PCL scaffolds as carriers for growth factor release

PubMed Central

Suárez-González, Darilis; Barnhart, Kara; Migneco, Francesco; Flanagan, Colleen; Hollister, Scott J.; Murphy, William L.

2011-01-01

In this study, we have developed mineral coatings on polycaprolactone scaffolds to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue in coatings formed in all HCO3 concentrations. Mineral coatings with increased HCO3 substitution showed more rapid dissolution kinetics in an environment deficient in calcium and phosphate but showed re-precipitation in an environment with the aforementioned ions. The mineral coating provided an effective mechanism for growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral mineral-coated PCL scaffolds. We also demonstrated sustained release of all growth factors with release kinetics that were strongly dependent in the solubility of the mineral coating. PMID:22014948

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival.

PubMed

Catrina, S-B; Lewitt, M; Massambu, C; Dricu, A; Grünler, J; Axelson, M; Biberfeld, P; Brismar, K

2005-04-25

Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130 +/- 27.6% (P < 0.05) similar to that induced by VEGF and with which it is additive (281 +/- 13%) (P < 0.05). Moreover, specific blockade of the receptor (either by alpha IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours.

Role of epidermal growth factor and transforming growth factor α in the developing stomach

PubMed Central

Kelly, E; Newell, S; Brownlee, K; Farmery, S; Cullinane, C; Reid, W; Jackson, P; Gray, S; Primrose, J; Lagopoulos, M

1997-01-01

AIMS—To determine whether epidermal growth factor (EGF) or the related transforming growth factor α (TGFα) may have a role in the developing human stomach; to substantiate the presence of EGF in human liquor in the non-stressed infant and whether EGF in amniotic fluid is maternally or fetally derived.
METHODS—The temporal expression and localisation of EGF, TGFα, and their receptors during fetal and neonatal life were examined in 20 fetal and five infant stomachs. Simultaneously, samples of amniotic fluid and fetal urine from 10 newborn infants were collected and assayed for EGF by radioimmunoassay.
RESULTS—EGF immunoreactivity was not noted in any of the specimens examined. In contrast, TGFα immunoreactivity was shown in mucous cells from 18 weeks of gestation onwards. EGF receptor immunoreactivity was seen on superficial mucous cells in gastric mucosa from 18 weeks of gestation onwards. The median concentration of EGF was 30 and 8.5 pg/ml in amniotic fluid and fetal urine, respectively, suggesting that EGF is not produced by the fetus.
CONCLUSIONS—This study adds weight to the hypothesis that swallowed EGF, probably produced by the amniotic membranes, and locally produced TGFα, may have a role in the growth and maturation of the human stomach.

 Keywords: epidermal growth factor; transforming growth factor α; EGF receptors; stomach PMID:9175944

Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

DTIC Science & Technology

2006-04-01

Schlingemann RO. 2004. In vivo angiogenic phenotype of endothelial cells and pericytes induced by vascular endothelial growth factor -a. J Histochem Cytochem...R, McDonald DM. Age-related changes in vascular endothelial growth factor dependency and angiopoietin-1-induced plasti- city of adult blood vessels...hematopoietic progenitor cells and their progeny in vivo . We used the basic fibroblast growth factor (bFGF)- induced mouse corneal neovascularization

Leukocyte- and platelet-rich fibrin (L-PRF) for long-term delivery of growth factor in rotator cuff repair: review, preliminary results and future directions.

PubMed

Zumstein, Matthias A; Berger, Simon; Schober, Martin; Boileau, Pascal; Nyffeler, Richard W; Horn, Michael; Dahinden, Clemens A

2012-06-01

Surgical repair of the rotator cuff repair is one of the most common procedures in orthopedic surgery. Despite it being the focus of much research, the physiological tendon-bone insertion is not recreated following repair and there is an anatomic non-healing rate of up to 94%. During the healing phase, several growth factors are upregulated that induce cellular proliferation and matrix deposition. Subsequently, this provisional matrix is replaced by the definitive matrix. Leukocyte- and platelet-rich fibrin (L-PRF) contain growth factors and has a stable dense fibrin matrix. Therefore, use of LPRF in rotator cuff repair is theoretically attractive. The aim of the present study was to determine 1) the optimal protocol to achieve the highest leukocyte content; 2) whether L-PRF releases growth factors in a sustained manner over 28 days; 3) whether standard/gelatinous or dry/compressed matrix preparation methods result in higher growth factor concentrations. 1) The standard L-PRF centrifugation protocol with 400 x g showed the highest concentration of platelets and leukocytes. 2) The L-PRF clots cultured in medium showed a continuous slow release with an increase in the absolute release of growth factors TGF-β1, VEGF and MPO in the first 7 days, and for IGF1, PDGF-AB and platelet activity (PF4=CXCL4) in the first 8 hours, followed by a decrease to close to zero at 28 days. Significantly higher levels of growth factor were expressed relative to the control values of normal blood at each culture time point. 3) Except for MPO and the TGFβ-1, there was always a tendency towards higher release of growth factors (i.e., CXCL4, IGF-1, PDGF-AB, and VEGF) in the standard/gelatinous- compared to the dry/compressed group. L-PRF in its optimal standard/gelatinous-type matrix can store and deliver locally specific healing growth factors for up to 28 days and may be a useful adjunct in rotator cuff repair.

Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1.

PubMed Central

Liu, C; Adamson, E; Mercola, D

1996-01-01

The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1. Images Fig. 1 Fig. 5 PMID:8876223

Identification of factors influencing the restoration of cyanobacteria-dominated biological soil crusts.

PubMed

Bu, Chongfeng; Wu, Shufang; Yang, Yongsheng; Zheng, Mingguo

2014-01-01

Biological soil crusts (BSCs) cover >35% of the Earth's land area and contribute to important ecological functions in arid and semiarid ecosystems, including erosion reduction, hydrological cycling, and nutrient cycling. Artificial rapid cultivation of BSCs can provide a novel alternative to traditional biological methods for controlling soil and water loss such as the planting of trees, shrubs, and grasses. At present, little is known regarding the cultivation of BSCs in the field due to lack of knowledge regarding the influencing factors that control BSCs growth. Thus, we determined the effects of various environmental factors (shade; watering; N, P, K, and Ca concentrations) on the growth of cyanobacteria-dominated BSCs from the Sonoran Desert in the southwestern United States. The soil surface changes and chlorophyll a concentrations were used as proxies of BSC growth and development. After 4 months, five factors were found to impact BSC growth with the following order of importance: NH4NO3 ≈ watering frequency>shading>CaCO3 ≈ KH2PO4. The soil water content was the primary positive factor affecting BSC growth, and BSCs that were watered every 5 days harbored greater biomass than those watered every 10 days. Groups that received NH4NO3 consistently exhibited poor growth, suggesting that fixed N amendment may suppress BSC growth. The effect of shading on the BSC biomass was inconsistent and depended on many factors including the soil water content and availability of nutrients. KH2PO4 and CaCO3 had nonsignificant effects on BSC growth. Collectively, our results indicate that the rapid restoration of BSCs can be controlled and realized by artificial "broadcasting" cultivation through the optimization of environmental factors.

Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.

PubMed

Liu, Junjun; Chen, Xiaosong; Ward, Toby; Mao, Yan; Bockhorn, Jessica; Liu, Xiaofei; Wang, Gen; Pegram, Mark; Shen, Kunwei

2016-02-01

Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor 2-positive breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhancing hair growth in male androgenetic alopecia by a combination of fractional CO2 laser therapy and hair growth factors.

PubMed

Huang, Yue; Zhuo, Fenglin; Li, Linfeng

2017-11-01

Laser therapy and growth factors have been used as alternative treatments for male androgenetic alopecia (MAA). The aim of this study is to determine the efficacy and safety of hair growth factors alone or combined with ablative carbon dioxide (CO 2 ) fractional laser therapy in MAA. Twenty-eight men were enrolled in this randomized half-split study based on a left-head to right-head pattern. Fractional CO 2 laser treatment was unilaterally performed; hair growth factors were bilaterally applied. Six sessions with 2-week intervals were performed. Global photographs and dermoscopy assessments were performed at the baseline and 4 months after first treatment. Global photographs underwent blinded review by three independent dermatologists. Scanning electron microscopy was used to compare changes in hair-follicle phase and hair-shaft diameter. Twenty-seven participants completed the 4-month treatment schedule. One patient was lost. Mean hair density increased from 114 ± 27 to 143 ± 25/cm 2 (P < 0.001) in the combined group and from 113 ± 24 to 134 ± 19/cm 2 in the growth factor group (P < 0.001). The mean change from baseline between two groups was also compared (P = 0.003). Global photographs showed improvement in 93% (25/27) patients in the combined group and 67% (18/27) patients in the growth factor group. Under scanning electron microscopy, hair follicles appeared to transition from telogen to anagen, and hair-shaft diameter increased in five randomly selected patients. Ablative fractional CO 2 laser combined with hair growth factors may serve as an alternative treatment for MAA in individuals unwilling/unable to undergo medical or surgical treatment.

A virally inactivated functional growth factor preparation from human platelet concentrates.

PubMed

Su, C-Y; Kuo, Y P; Lin, Y C; Huang, C-T; Tseng, Y H; Burnouf, T

2009-08-01

Human platelet growth factors (HPGF) are essential for tissue regeneration and may replace fetal bovine serum (FBS) in cell therapy. No method for the manufacture of standardized virally inactivated HPGF has been developed yet. Platelet concentrates (PC) were subjected to solvent/detergent (S/D) treatment (1% TnBP/1% Triton X-45), oil extraction, hydrophobic interaction chromatography and sterile filtration. Platelet-derived growth factor (PDGF)-AB, -BB and -AA, transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1) and vascular endothelium growth factor (VEGF) were measured by ELISA. Composition in proteins and lipids was determined, protein profiles were obtained by SDS-PAGE, and TnBP and Triton X-45 were assessed by gas chromatography and high-performance liquid chromatography, respectively. Cell growth promoting activity of HPGF was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay using human embryonic kidney (HEK293A) fibroblast and Statens Seruminstitute rabbit corneal (SIRC) epithelial cell lines. The GF preparation contained a mean of 16.66, 2.04, 1.53, 72.19, 0.33, 48.59 and 0.44 ng/ml of PDGF-AB, -BB, -AA, TGF-beta1, EGF, IGF-1 and VEGF, respectively. The protein profile was typical of platelet releasates and had less than 2 p.p.m. of residual S/D agents. MTS assay of HEK293A and SIRC cultures showed that the GF preparation at 10% and 0.1% (v/v), respectively, could successfully replace 10% FBS for cell proliferation. Cell-stimulating activity of HPGF on HEK293A was over twice that of PC releasates. STANDARDIZED and functional virally inactivated HPGF can be prepared from human PC for possible applications in cell therapy and regenerative medicine.

Quinones are growth factors for the human gut microbiota.

PubMed

Fenn, Kathrin; Strandwitz, Philip; Stewart, Eric J; Dimise, Eric; Rubin, Sarah; Gurubacharya, Shreya; Clardy, Jon; Lewis, Kim

2017-12-20

The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an "induced" isolate formed a gradient of growth around a cultivatable "helper." This set included two novel species Faecalibacterium sp. KLE1255-belonging to the anti-inflammatory Faecalibacterium genus-and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species.

New microbial growth factor

NASA Technical Reports Server (NTRS)

Bok, S. H.; Casida, L. E., Jr.

1977-01-01

A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

Specific protein supplementation using soya, casein or whey differentially affects regional gut growth and luminal growth factor bioactivity in rats; implications for the treatment of gut injury and stimulating repair.

PubMed

Marchbank, Tania; Mandir, Nikki; Calnan, Denis; Goodlad, Robert A; Podas, Theo; Playford, Raymond J

2018-01-24

Modulation of regional growth within specific segments of the bowel may have clinical value for several gastrointestinal conditions. We therefore examined the effects of different dietary protein sources on regional gut growth and luminal growth factor bioactivity as potential therapies. Rats were fed for 14 days on isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which is known to cause gut atrophy), ED supplemented with casein or whey or a soya protein-rich feed. Effects on regional gut growth and intraluminal growth factor activity were then determined. Despite calorie intake being similar in all groups, soya rich feed caused 20% extra total body weight gain. Stomach weight was highest on soya and casein diets. Soya enhanced diet caused greatest increase in small intestinal weight and preserved luminal growth factor activity at levels sufficient to increase proliferation in vitro. Regional small intestinal proliferation was highest in proximal segment in ED fed animals whereas distal small intestine proliferation was greater in soya fed animals. Colonic weight and proliferation throughout the colon was higher in animals receiving soya or whey supplemented feeds. We conclude that specific protein supplementation with either soya, casein or whey may be beneficial to rest or increase growth in different regions of the bowel through mechanisms that include differentially affecting luminal growth factor bioactivity. These results have implications for targeting specific regions of the bowel for conditions such as Crohn's disease and chemotherapy.

Periods of Child Growth up to age 8 Years in Ethiopia, India, Peru and Vietnam: Key Distal Household and Community Factors

PubMed Central

Schott, Whitney B.; Crookston, Benjamin T.; Lundeen, Elizabeth A.; Stein, Aryeh D.; Behrman, Jere R.

2013-01-01

Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7,266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40 to 71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26 to 47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers’ height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child’s starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex. PMID:23769211

Posttraumatic growth in patients who survived cardiac surgery: the predictive and mediating roles of faith-based factors.

PubMed

Ai, Amy L; Hall, Daniel; Pargament, Kenneth; Tice, Terrence N

2013-04-01

Despite the growing knowledge of posttraumatic growth, only a few studies have examined personal growth in the context of cardiac health. Similarly, longitudinal research is lacking on the implications of religion/spirituality for patients with advanced cardiac diseases. This paper aims to explore the effect of preoperative religious coping on long-term postoperative personal growth and potential mediation in this effect. Analyses capitalized on a preoperative survey and medical indices from the Society of Thoracic Surgeons' National Database of patients undergoing cardiac surgery. Participants in the current follow-up study completed a mailed survey 30 months after surgery. Hierarchical regression analysis was performed to evaluate the extent to which preoperative use of religious coping predicted growth at follow-up, after controlling for key demographics, medical indices, mental health, and protective factors. Predictors of posttraumatic growth at follow-up were positive religious coping and a living status without a partner. Medical indices, optimistic expectations, social support, and other religious factors were unrelated to posttraumatic growth. Including religious factors diminished effects of gender, age, and race. Including perceived spiritual support completely eliminated the role of positive religious coping, indicating mediation. Preoperative positive religious coping may have a long-term effect on postoperative personal growth, explainable by higher spiritual connections as a part of significance-making. These results suggest that spirituality may play a favorable role in cardiac patients' posttraumatic growth after surviving a life-altering operation. The elimination of demographic effects may help explain previously mixed findings concerning the association between these factors and personal growth.

Periods of child growth up to age 8 years in Ethiopia, India, Peru and Vietnam: key distal household and community factors.

PubMed

Schott, Whitney B; Crookston, Benjamin T; Lundeen, Elizabeth A; Stein, Aryeh D; Behrman, Jere R

2013-11-01

Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40-71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26-47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers' height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child's starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex. Copyright © 2013 Elsevier Ltd. All rights reserved.

Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

PubMed

Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

2017-11-02

The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p < .001). Angiogenesis occurs as a placental response to intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

Effects of Lycopersicon esculentum extract on hair growth and alopecia prevention.

PubMed

Choi, Jae-Suk; Jung, Sung Kyu; Jeon, Min-Hee; Moon, Jin-Nam; Moon, Woi-Sook; Ji, Yi-Hwa; Choi, In Soon; Wook Son, Sang

2013-01-01

To evaluate the potential hair growth-promoting activity and the expression of cell growth factors of Lycopersicon esculentum extracts, each 3% (w/w) of ethyl acetate extract (EAE), and supercritical CO2 extract (SCE) of L. esculentum and isolated lycopene Tween 80 solution (LTS) and test hair tonic (THT) containing LTS were applied on the dorsal skin of C57BL/6 mice, once a day for 4 weeks. At week 4, LTS and THT exhibited hair growth-promoting potential similar to that of 3% minoxidil as a positive control (PC). Further, in the LTS group, a significant increase of mRNA expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor, and insulin-like growth factor-1 (IGF-1) was observed than PC, as well as the negative control (NC). In the THT group, increases in IGF-1 and decrease in VEGF and transforming growth factor-β expression were significant over the NC. In a histological examination in the THT group, the induction of anagen stage of hair follicles was faster than that of NC. In the Draize skin irritation study for THT, no observable edema or erythema was observed on all four sectors in the back skin after exposure for 24 or 72 h for any rabbit. Therefore, this study provides reasonable evidence that L. esculentum extracts promote hair growth and suggests that applications could be found in hair loss treatments without skin irritation at moderate doses.

Expansion and redifferentiation of chondrocytes from osteoarthritic cartilage: cells for human cartilage tissue engineering.

PubMed

Hsieh-Bonassera, Nancy D; Wu, Iwen; Lin, Jonathan K; Schumacher, Barbara L; Chen, Albert C; Masuda, Koichi; Bugbee, William D; Sah, Robert L

2009-11-01

To determine if selected culture conditions enhance the expansion and redifferentiation of chondrocytes isolated from human osteoarthritic cartilage with yields appropriate for creation of constructs for treatment of joint-scale cartilage defects, damage, or osteoarthritis. Chondrocytes isolated from osteoarthritic cartilage were analyzed to determine the effects of medium supplement on cell expansion in monolayer and then cell redifferentiation in alginate beads. Expansion was assessed as cell number estimated from DNA, growth rate, and day of maximal growth. Redifferentiation was evaluated quantitatively from proteoglycan and collagen type II content, and qualitatively by histology and immunohistochemistry. Using either serum or a growth factor cocktail (TFP: transforming growth factor beta1, fibroblast growth factor 2, and platelet-derived growth factor type bb), cell growth rate in monolayer was increased to 5.5x that of corresponding conditions without TFP, and cell number increased 100-fold within 17 days. In subsequent alginate bead culture with human serum or transforming growth factor beta1 and insulin-transferrin-selenium-linoleic acid-bovine serum albumin, redifferentiation was enhanced with increased proteoglycan and collagen type II production. Effects of human serum were dose dependent, and 5% or higher induced formation of chondron-like structures with abundant proteoglycan-rich matrix. Chondrocytes from osteoarthritic cartilage can be stimulated to undergo 100-fold expansion and then redifferentiation, suggesting that they may be useful as a cell source for joint-scale cartilage tissue engineering.

Analysis of private health insurance premium growth rates: 1985-1992.

PubMed

Feldstein, P J; Wickizer, T M

1995-10-01

The rate of increase in health care expenditures has been a central policy concern for well over a decade, yet little empirical research has been conducted to examine expenditure growth rates. This study analyzed health insurance premium growth rates for a selected sample of 95 insured groups over the period 1985 to 1992. During this time, premiums increased by approximately 150% in nominal terms and by 45% in real terms. The observed rate of growth was not constant over time, however. The most rapid growth occurred during the years 1986 to 1989; thereafter, the rate of increase in premiums declined. Multivariate analysis was conducted to assess the effects on premium growth rates of selected variables representing insurance benefit design features, market competitive factors, insurance system factors, and group-specific factors. In addition to the percentage increase in benefit payments, other factors found to affect premium growth rates were health maintenance organization market penetration, deductible level, the coinsurance rate, and state insurance mandates. Further, this analysis suggests that the insurance underwriting cycle may play an important role in influencing insurance premium growth rates. These results support the belief that health maintenance organization induced competition has potential to control the rate of increase in health care costs.

Creep crack growth by grain boundary cavitation under monotonic and cyclic loading

NASA Astrophysics Data System (ADS)

Wen, Jian-Feng; Srivastava, Ankit; Benzerga, Amine; Tu, Shan-Tung; Needleman, Alan

2017-11-01

Plane strain finite deformation finite element calculations of mode I crack growth under small scale creep conditions are carried out. Attention is confined to isothermal conditions and two time histories of the applied stress intensity factor: (i) a monononic increase to a plateau value subsequently held fixed; and (ii) a cyclic time variation. The crack growth calculations are based on a micromechanics constitutive relation that couples creep deformation and damage due to grain boundary cavitation. Grain boundary cavitation, with cavity growth due to both creep and diffusion, is taken as the sole failure mechanism contributing to crack growth. The influence on the crack growth rate of loading history parameters, such as the magnitude of the applied stress intensity factor, the ratio of the applied minimum to maximum stress intensity factors, the loading rate, the hold time and the cyclic loading frequency, are explored. The crack growth rate under cyclic loading conditions is found to be greater than under monotonic creep loading with the plateau applied stress intensity factor equal to its maximum value under cyclic loading conditions. Several features of the crack growth behavior observed in creep-fatigue tests naturally emerge, for example, a Paris law type relation is obtained for cyclic loading.

Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature

PubMed Central

Aldag, Caroline; Nogueira Teixeira, Diana; Leventhal, Phillip S

2016-01-01

Skin aging is primarily due to alterations in the dermal extracellular matrix, especially a decrease in collagen I content, fragmentation of collagen fibrils, and accumulation of amorphous elastin material, also known as elastosis. Growth factors and cytokines are included in several cosmetic products intended for skin rejuvenation because of their ability to promote collagen synthesis. Matrikines and matrikine-like peptides offer the advantage of growth factor-like activities but better skin penetration due to their much smaller molecular size. In this review, we summarize the commercially available products containing growth factors, cytokines, and matrikines for which there is evidence that they promote skin rejuvenation. PMID:27877059

Origin of platelet-derived growth factor in megakaryocytes in guinea pigs.

PubMed Central

Chernoff, A; Levine, R F; Goodman, D S

1980-01-01

Growth factor activity, as determined by the stimulation of [3H]thymidine incorporation into the DNA of quiescent 3T3 cells in culture, was found in lysates of guinea pig platelets and megakaryocytes. Quantitative dilution studies demonstrated that, of the cells present in the guinea pig bone marrow, only the megakaryocyte possessed quantitatively significant growth factor activity. The amount of activity present in one megakaryocyte was equivalent to that present in 1,000-5,000 platelets, a value approximately comparable to the number of platelets shed from a single megakaryocyte. It is suggested that guinea pig platelet-derived growth factor has its origin in the megakaryocyte. PMID:7358851

The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

PubMed

Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

2014-06-01

The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, p<0.001; 44.1 ± 46.8 ng/ml vs. 22.8 ± 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, p<0.001) and acute renal failure (85.5 ± 75.0 ng/ml vs. 31.2 ± 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 ± 57.5 ng/ml vs. 18.7 ± 6.4 ng/ml, p = 0.019; 57.6 ± 57.5 ng/ml vs. 25.2 ± 14.9 ng/ml, p = 0.006; 57.6 ± 57.5 ng/ml vs. 30.5 ± 21.3 ng/ml, p = 0.017, respectively). Serum connective tissue growth factor levels were significantly higher in those with both active/chronic lesions than those in those with active lesions only in either class IV (84.9 ± 69.6 ng/ml vs. 40.0 ± 40.2 ng/ml, p = 0.001) or in combination of class III and IV lupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, p<0.001) and positively associated with interstitial inflammation (r = 0.309, p = 0.002) and interstitial fibrosis (r = 0.287, p = 0.004). Serum connective tissue growth factor level was a risk factor for doubling of serum creatinine in lupus nephritis (p<0.001, hazard ratio = 1.015, 95% confidence intervals 1.008-1.022) in univariate analysis. Serum connective tissue growth factor levels were significantly higher in lupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Predictive factors for intrauterine growth restriction

PubMed Central

Albu, AR; Anca, AF; Horhoianu, VV; Horhoianu, IA

2014-01-01

Abstract Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies. Abbreviations: SGA = small for gestational age; IUGR = intrauterine growth restriction; FGR = fetal growth restriction; IUFD = intrauterine fetal demise; HIV = human immunodeficiency virus; PAPP-A = pregnancy associated plasmatic protein A; β-hCG = beta human chorionic gonadotropin; MoM = multiple of median; ADAM-12 = A-disintegrin and metalloprotease 12; PP-13 = placental protein 13; VEGF = vascular endothelial growth factor; PlGF = placental growth factor; sFlt-1 = soluble fms-like tyrosine kinase-1; UAD = uterine arteries Doppler ultrasound; RI = resistence index; PI = pulsatility index; VOCAL = Virtual Organ Computer–Aided Analysis software; VI = vascularization index; FI = flow index; VFI = vascularization flow index; PQ = placental quotient PMID:25408721