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1

Stem Cells  

MedlinePLUS

Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

2

Effects of nanotopography on stem cell phenotypes  

PubMed Central

Stem cells are unspecialized cells that can self renew indefinitely and differentiate into several somatic cells given the correct environmental cues. In the stem cell niche, stem cell-extracellular matrix (ECM) interactions are crucial for different cellular functions, such as adhesion, proliferation, and differentiation. Recently, in addition to chemical surface modifications, the importance of nanometric scale surface topography and roughness of biomaterials has increasingly becoming recognized as a crucial factor for cell survival and host tissue acceptance in synthetic ECMs. This review describes the influence of nanotopography on stem cell phenotypes.

Ravichandran, Rajeswari; Liao, Susan; Ng, Clarisse CH; Chan, Casey K; Raghunath, Michael; Ramakrishna, Seeram

2009-01-01

3

STEM CELLS  

PubMed Central

Two independent studies show that, if push comes to shove, differentiated cells of the stomach and lung can act as adult stem cells generating various cell types of the tissue, including a pool of stem cells.

Desai, Tushar J.; Krasnow, Mark A.

2014-01-01

4

Effects of Simulated Microgravity on Embryonic Stem Cells  

PubMed Central

There have been many studies on the biological effects of simulated microgravity (SMG) on differentiated cells or adult stem cells. However, there has been no systematic study on the effects of SMG on embryonic stem (ES) cells. In this study, we investigated various effects (including cell proliferation, cell cycle distribution, cell differentiation, cell adhesion, apoptosis, genomic integrity and DNA damage repair) of SMG on mouse embryonic stem (mES) cells. Mouse ES cells cultured under SMG condition had a significantly reduced total cell number compared with cells cultured under 1 g gravity (1G) condition. However, there was no significant difference in cell cycle distribution between SMG and 1G culture conditions, indicating that cell proliferation was not impaired significantly by SMG and was not a major factor contributing to the total cell number reduction. In contrast, a lower adhesion rate cultured under SMG condition contributed to the lower cell number in SMG. Our results also revealed that SMG alone could not induce DNA damage in mES cells while it could affect the repair of radiation-induced DNA lesions of mES cells. Taken together, mES cells were sensitive to SMG and the major alterations in cellular events were cell number expansion, adhesion rate decrease, increased apoptosis and delayed DNA repair progression, which are distinct from the responses of other types of cells to SMG.

Jiang, Yuanda; Hang, Haiying

2011-01-01

5

Mesenchymal stem cell effects on T-cell effector pathways  

Microsoft Academic Search

Mesenchymal stem (stromal) cells (MSCs) are rare, multipotent progenitor cells that can be isolated and expanded from bone\\u000a marrow and other tissues. Strikingly, MSCs modulate the functions of immune cells, including T cells, B cells, natural killer\\u000a cells, monocyte\\/macrophages, dendritic cells, and neutrophils. T cells, activated to perform a range of different effector\\u000a functions, are the primary mediators of many

Michelle M Duffy; Thomas Ritter; Rhodri Ceredig; Matthew D Griffin

2011-01-01

6

Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model  

Microsoft Academic Search

We investigated the effect of human bone marrow-derived mesenchymal stem cells on engraftment of human umbilical cord blood\\u000a CD34+ cells and acute myelogenous leukemia cells and also assessed the homing capability of MSCs. Forty-two NOD\\/SCID mice were\\u000a administered sublethal irradiation followed by various cell doses of intravenous UCB CD34+ cells with or without MSCs. Another 12 NOD\\/SCID mice were also

Seung-Tae Lee; Hoyoung Maeng; Yong-Joon Chwae; Duk Jae Oh; Yong-Man Kim; Woo Ick Yang

2008-01-01

7

Immunomodulatory effect of canine periodontal ligament stem cells on allogenic and xenogenic peripheral blood mononuclear cells  

PubMed Central

Purpose The aim of this study was to investigate the immunomodulatory effects of canine periodontal ligament stem cells on allogenic and xenogenic immune cells in vitro. Methods Mixed cell cultures consisting of canine stem cells (periodontal ligament stem cells and bone marrow stem cells) and allogenic canine/xenogenic human peripheral blood mononuclear cells (PBMCs) were established following the addition of phytohemagglutinin. The proliferation of PBMCs was evaluated using the MTS assay. The cell division of PBMCs was analyzed using the CFSE assay. The apoptosis of PBMCs was assessed using the trypan blue uptake method. Results Periodontal ligament stem cells and bone marrow stem cells inhibited the proliferation of allogenic and xenogenic PBMCs. Both periodontal ligament stem cells and bone marrow stem cells suppressed the cell division of PBMCs despite the existence of a mitogen. No significant differences in the percentages of apoptotic PBMCs were found among the groups. Conclusions Canine periodontal ligament stem cells have an immunomodulatory effect on allogenic and xenogenic PBMCs. This effect is not a product of apoptosis of PBMCs but is caused by the inhibition of cell division of PBMCs.

Kim, Hak-Sung; Kim, Kyoung-Hwa; Kim, Su-Hwan; Kim, Young-Sung; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Ku, Young; Rhyu, In-Chul; Chung, Chong-Pyoung

2010-01-01

8

Radiation-Induced Bystander Effects in Cultured Human Stem Cells  

Microsoft Academic Search

BackgroundThe radiation-induced “bystander effect” (RIBE) was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR). RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem

Mykyta V. Sokolov; Ronald D. Neumann; Henning Ulrich

2010-01-01

9

Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior  

NASA Astrophysics Data System (ADS)

A key process in organ homeostasis is the mobilization of stem cells out of their niches. We show through analysis of mouse models that telomere length, as well as the catalytic component of telomerase, Tert, are critical determinants in the mobilization of epidermal stem cells. Telomere shortening inhibited mobilization of stem cells out of their niche, impaired hair growth, and resulted in suppression of stem cell proliferative capacity in vitro. In contrast, Tert overexpression in the absence of changes in telomere length promoted stem cell mobilization, hair growth, and stem cell proliferation in vitro. The effects of telomeres and telomerase on stem cell biology anticipate their role in cancer and aging.

Flores, Ignacio; Cayuela, María L.; Blasco, María A.

2005-08-01

10

Effect of ceramide on mesenchymal stem cell differentiation toward adipocytes.  

PubMed

Proinflammatory cytokines such as tumor necrosis factor (TNF) alpha are well known to inhibit adipocyte differentiation. TNF-alpha triggers ceramide synthesis through binding of TNF-alpha to its p55 receptor. Therefore, ceramide is implicated in many of the multiple signaling pathways initiated by TNF-alpha. In breast tissue engineering, it is important to know how to modulate adipocyte differentiation of the stem cells with exogenous additives like ceramide in vitro. We hypothesized that stem cell adipogenesis could be retained in TNF-alpha-treated preadipocytes in which ceramide synthesis was blocked and that exogenous ceramide could inhibit adipocyte differentiation. We first studied the effect of ceramide synthase inhibitor, Fumonisin B2, on the adipogenesis of murine mesenchymal stem cells (D1 cells), treated with TNF-alpha. We then studied the effect of specific exogenous C6-ceramide on D1 cell viability and differentiation. It was found that 1 ng/ml of TNF-alpha significantly inhibited D1 cell adipogenesis. Cells treated with 5 microM of Fumonisin B2 were able to undergo adipogenesis, even when treated with TNF-alpha. High concentrations of exogenous C6-ceramide (>50 microM) had an inhibitory effect, not only on the pre-confluent proliferation of the D1 cells but also on the post-confluent cell viability. High concentrations of C6-ceramide (>50 microM) also inhibited mitotic clonal expansion when D1 cell differentiation was induced by the addition of an adipogenic hormonal cocktail. C6-ceramide at low concentrations (10-25 microM) inhibited lipid production in D1 cells, demonstrated by decreased levels of both total triglyceride content and specific fatty acid composition percentages. Genetic expression of peroxisome proliferator-activated receptor (PPAR) gamma and aP2 in D1 cells was reduced by C6-ceramide treatment. CCAAT/enhancer-binding protein (C/EBP) beta levels in D1 cells were reduced by C6-ceramide treatment during early differentiation; PPARgamma and aP2 protein levels were reduced at terminal differentiation. C6-ceramide at lower concentrations also decreased lipid accumulation of differentiating D1 cells. Our results suggest that ceramide synthase inhibitor retains the adipogenic potential of TNF-alpha-treated mesenchymal stem cells, while exogenous ceramide at lower concentrations inhibit the adipogenesis of mesenchymal stem cells. Ceramide, therefore, could be a modulator candidate in breast tissue engineering strategies. PMID:19165630

Xu, F; Yang, C-C; Gomillion, C; Burg, K J L

2010-01-01

11

Paracrine effects of stem cells in wound healing and cancer progression (Review).  

PubMed

Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific stem cells to rebuild damaged tissue and cancer stem cells to initiate and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer, facilitate wound healing and support cancer progression primarily by secreting bioactive factors. There is now growing evidence that, like mesenchymal stem cells, also tissue-specific and cancer stem cells manipulate their environment by paracrine actions. Soluble factors and microvesicles released by these stem cells have been shown to protect recipient cells from apoptosis and to stimulate neovascularization. These paracrine mechanisms may allow stem cells to orchestrate wound healing and cancer progression. Hence, understanding these stem cell-driven paracrine effects may help to improve tissue regeneration and cancer treatment. PMID:24728412

Dittmer, Jürgen; Leyh, Benjamin

2014-06-01

12

Paracrine effects of stem cells in wound healing and cancer progression  

PubMed Central

Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific stem cells to rebuild damaged tissue and cancer stem cells to initiate and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer, facilitate wound healing and support cancer progression primarily by secreting bioactive factors. There is now growing evidence that, like mesenchymal stem cells, also tissue-specific and cancer stem cells manipulate their environment by paracrine actions. Soluble factors and microvesicles released by these stem cells have been shown to protect recipient cells from apoptosis and to stimulate neovascularization. These paracrine mechanisms may allow stem cells to orchestrate wound healing and cancer progression. Hence, understanding these stem cell-driven paracrine effects may help to improve tissue regeneration and cancer treatment.

DITTMER, JURGEN; LEYH, BENJAMIN

2014-01-01

13

Effective elimination of cancer stem cells by magnetic hyperthermia.  

PubMed

Cancer stem cells (CSCs) are a subpopulation of cancer cells that have stem cell-like properties and are thought to be responsible for tumor drug resistance and relapse. Therapies that can effectively eliminate CSCs will, therefore, likely inhibit tumor recurrence. The objective of our study was to determine the susceptibility of CSCs to magnetic hyperthermia, a treatment that utilizes superparamagnetic iron oxide nanoparticles placed in an alternating magnetic field to generate localized heat and achieve selective tumor cell kill. SPIO NPs having a magnetite core of 12 nm were used to induce magnetic hyperthermia in A549 and MDA-MB-231 tumor cells. Multiple assays for CSCs, including side population phenotype, aldehyde dehydrogenase expression, mammosphere formation, and in vivo xenotransplantation, indicated that magnetic hyperthermia reduced or, in some cases, eliminated the CSC subpopulation in treated cells. Interestingly, conventional hyperthermia, induced by subjecting cells to elevated temperature (46 °C) in a water bath, was not effective in eliminating CSCs. Our studies show that magnetic hyperthermia has pleiotropic effects, inducing acute necrosis in some cells while stimulating reactive oxygen species generation and slower cell kill in others. These results suggest the potential for lower rates of tumor recurrence after magnetic hyperthermia compared to conventional cancer therapies. PMID:23432410

Sadhukha, Tanmoy; Niu, Lin; Wiedmann, Timothy Scott; Panyam, Jayanth

2013-04-01

14

Stem Cell Basics  

MedlinePLUS

... cells? What are embryonic stem cells? What are adult stem cells? What are the similarities and differences between embryonic and adult stem cells? What are induced pluripotent stem cells? What are ...

15

Testicular germline stem cells  

Microsoft Academic Search

Stem cells have the ability to both differentiate into other mature cell types and maintain an undifferentiated state by self-renewal. These unique properties form the basis for stem cell use in organ replacement and tissue regeneration in clinical medicine. Currently, embryonic stem cells are the best-studied stem cell type. However alternative stem cells such as induced pluripotent stem cells and

Kehkooi Kee; Renee A. Reijo Pera; Paul J. Turek

2010-01-01

16

The effects of graphene nanostructures on mesenchymal stem cells.  

PubMed

We report the effects of two-dimensional graphene nanostructures; graphene nano-onions (GNOs), graphene oxide nanoribbons (GONRs), and graphene oxide nanoplatelets (GONPs) on viability, and differentiation of human mesenchymal stem cells (MSCs). Cytotoxicity of GNOs, GONRs, and GONPs dispersed in distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)] (DSPE-PEG), on adipose derived mesenchymal stem cells (adMSCs), and bone marrow-derived mesenchymal stem cells (bmMSCs) was assessed by AlamarBlue and Calcein AM viability assays at concentrations ranging from 5 to 300 ?g/ml for 24 or 72 h. Cytotoxicity of the 2D graphene nanostructures was found to be dose dependent, not time dependent, with concentrations less than 50 ?g/ml showing no significant differences compared to untreated controls. Differentiation potential of adMSCs to adipocytes and osteoblasts, - characterized by Oil Red O staining and elution, alkaline phosphatase activity, calcium matrix deposition and Alizarin Red S staining - did not change significantly when treated with the three graphene nanoparticles at a low (10 ?g/ml) and high (50 ?g/ml) concentration for 24 h. Transmission electron microscopy (TEM) and confocal Raman spectroscopy indicated cellular uptake of only GNOs and GONPs. The results lay the foundation for the use of these nanoparticles at potentially safe doses as ex vivo labels for MSC-based imaging and therapy. PMID:24674462

Talukdar, Yahfi; Rashkow, Jason T; Lalwani, Gaurav; Kanakia, Shruti; Sitharaman, Balaji

2014-06-01

17

Effect of tripeptides on lymphoid and stem cells.  

PubMed

Tripeptides T-36 and, particularly, T-38 in concentrations of 0.1, 1, and 10 ng/ml inhibited proliferation of primary trypsinized embryonic mesenchymal stem cells, rat transplantable KF-1 fibroblasts, and human erythromyelosis K-562 cells. Inhibition of proliferation in embryonic and immortalized cells under the influence of tripeptides probably reflects antitumor activity of these substances. Tripeptides had no effect on lymphocyte survival and their adhesive, cytotoxic, and induced proliferative activities. T-36 did not modulate the proliferative properties of erythromyelosis K-562 cells. Tripeptides did not change engulfment activity and spontaneous and induced bactericidal activities of granulocytes. T-36 in a concentration of 0.1 ng/ml increased spontaneous proliferation of normal lymphocytes. These data suggest that tripeptides stimulate nontumor immune cells in adult people. PMID:22485217

Khavinson, V Kh; Nikolsky, I S; Nikolskaya, V V; Zubov, D A; Galickaya, S N; Taranuha, L I; Semenova, Ya-M A; Lisica, N A; Linkova, N S; Butenko, G M

2011-10-01

18

Stem cells, cancer, and cancer stem cells  

Microsoft Academic Search

Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells

Tannishtha Reya; Sean J. Morrison; Michael F. Clarke; Irving L. Weissman

2001-01-01

19

Intraoperative Stem Cell Therapy  

PubMed Central

Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium.

Coelho, Monica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

2013-01-01

20

Effect of optogenetic stimulus on the proliferation and cell cycle progression of neural stem cells.  

PubMed

Modulation of stem cell proliferation is a crucial aspect of neural developmental biology and regenerative medicine. To investigate the effect of optical stimulation on neural stem cell proliferation, cells transduced with channelrhodopsin-2 (ChR2) were used to analyze changes in cell proliferation and cell cycle distribution after light stimulation. Blue light significantly inhibited cell proliferation and affected the cell cycle, which increased the percentage of cells in G1 phase and reduced the percentage in S phase. It is likely that the influence of blue light on cell proliferation and the cell cycle was mediated by membrane depolarization, which induced accumulation of p21 and p27 proteins. Our data provide additional specific evidence that membrane depolarization may inhibit neural stem cell proliferation. PMID:24748510

Wang, Shao Jun; Weng, Chuan Huang; Xu, Hai Wei; Zhao, Cong Jian; Yin, Zheng Qin

2014-06-01

21

Stem Cell Transplants  

MedlinePLUS

What Are Stem Cells? As you probably remember from biology class, every living thing is made up of cells — including the human body. ... can become new cells like this. Blood Stem Cells When you hear about stem cell transplants, they ...

22

Immunomodulative effects of mesenchymal stem cells derived from human embryonic stem cells in vivo and in vitro  

Microsoft Academic Search

Objective  Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs). The\\u000a present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs), but also\\u000a describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl4)-induced liver inflammation model.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Undifferentiated hESCs were treated

Zhou Tan; Zhong-yuan Su; Rong-rong Wu; Bin Gu; Yu-kan Liu; Xiao-li Zhao; Ming Zhang

2011-01-01

23

Effect of Stem Cell Therapy on Adriamycin Induced Tubulointerstitial Injury  

PubMed Central

Background and Objectives It was postulated that adriamycin (ADR) induce renal tubulointerstitial injury. Clinicians are faced with a challenge in producing response in renal patients and slowing or halting the evolution towards kidney failure. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on tubular renal damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. Methods and Results Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy, vacuolated cytoplasm, dark nuclei, detached epithelial lining and desquamated nuclei were noticed in few collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of CT showing desquamated nuclei and mean value of serum creatinine revealed significant difference in ADR group. The mean area% of Prussian blue+ve cells and that of CD105 +ve cells measured in subgroup S1 denoted a significant increase compared to subgroups S2 and S3. Conclusions ADR induced tubulointerstitial damage that regressed in response to cord blood HMSC therapy.

Zickri, Maha Baligh; Zaghloul, Somaya; Farouk, Mira; Fattah, Marwa Mohamed Abdel

2012-01-01

24

Effects of Hematopoietic Stem Cell Age on CML Disease Progression.  

National Technical Information Service (NTIS)

CML results from a chromosomal translocation in hematopoietic stem cells (HSC), yet the disease primarily presents as a myeloid hyperplasia with relatively infrequent lymphoid involvement. We proposed that age-associated defects in the potential of HSC to...

K. Dorshkind

2006-01-01

25

[Effective cryopreservation of human embryonic stem cells by programmed freezing].  

PubMed

Cryopreservation of human embryonic stem cells is an important and unsolved problem. A computer-controlled programmable cooler was used in the preservation of ES cells. Several effects have been experimentally studied, which include the cooling rates, the temperature of seeding, the temperatures before the samples being plunged into liquid nitrogen, and the cryoprotective agents. It was found that the favorable constitution of cryoprotective agents was Me2SO+ FBS+DMEM(1:3:6, v/v/v) with cooling protocol of -0.5 degrees C/min from 0 degrees C to -35 degrees C (seeding at -10 degrees C), and being plunged into the liquid nitrogen immediately. The high survival rate (81.8%) was obtained. PMID:16044919

Yang, Peng Fei; Tsung, Hsiao Chien; Cheng, Qi Kang; Hua, Tse Chao; Wu, Chun Fang; Cao, Yi Lin

2005-06-01

26

Effects of Hemodynamic Forces on the Vascular Differentiation of Stem Cells: Implications for Vascular Graft Engineering  

NASA Astrophysics Data System (ADS)

Although the field of vascular tissue engineering has made tremendous advances in the past decade, several complications have yet to be overcome in order to produce biocompatible small-diameter vascular conduits with long-term patency. Stem cells and progenitor cells represent potential cell sources in the development of autologous (or allogeneic), nonthrombogenic vascular grafts with mechanical properties comparable to native blood vessel. However, a better understanding of the effects of mechanical forces on stem cells and progenitor cells is needed to properly utilize these cells for tissue engineering applications. In this chapter, we discuss the current understanding of the effects of hemodynamic forces on the differentiation and function of adult stem cells, embryonic stem cells, and progenitor cells. We also review the use of stem cells and progenitor cells in vascular graft engineering.

Diop, Rokhaya; Li, Song

27

Immunotherapy following hematopoietic stem cell transplantation: potential for synergistic effects  

PubMed Central

Hematopoietic stem cell transplantation (HSCT) is a particularly important treatment for hematologic malignancies. Unfortunately, following allogeneic HSCT, graft-versus-host disease, immunosuppression and susceptibility to opportunistic infections remain among the most substantial problems restricting the efficacy and use of this procedure, particularly for cancer. Adoptive immunotherapy and/or manipulation of the graft offer ways to attack residual cancer as well as other transplant-related complications. Recent exciting discoveries have demonstrated that HSCT could be expanded to solid tissue cancers with profound effects on the effectiveness of adoptive immunotherapy. This review will provide a background regarding HSCT, discuss the complications that make it such a complex treatment procedure following up with current immunotherapeutic strategies and discuss emerging approaches in applying immunotherapy in HSCT for cancer.

Bouchlaka, Myriam N; Redelman, Doug; Murphy, William J

2011-01-01

28

The Effect of Laser Irradiation on Adipose Derived Stem Cell Proliferation and Differentiation  

NASA Astrophysics Data System (ADS)

There are two fundamental types of stem cells: Embryonic Stem cells and Adult Stem cells. Adult Stem cells have a more restricted potential and can usually differentiate into a few different cell types. In the body these cells facilitate the replacement or repair of damaged or diseased cells in organs. Low intensity laser irradiation was shown to increase stem cell migration and stimulate proliferation and it is thought that treatment of these cells with laser irradiation may increase the stem cell harvest and have a positive effect on the viability and proliferation. Our research is aimed at determining the effect of laser irradiation on differentiation of Adipose Derived Stem Cells (ADSCs) into different cell types using a diode laser with a wavelength of 636 nm and at 5 J/cm2. Confirmation of stem cell characteristics and well as subsequent differentiation were assessed using Western blot analysis and cellular morphology supported by fluorescent live cell imaging. Functionality of subsequent differentiated cells was confirmed by measuring adenosine triphosphate (ATP) production and cell viability.

Abrahamse, H.; de Villiers, J.; Mvula, B.

2009-06-01

29

Cryopreservation Effects on Wharton's Jelly Stem Cells Proteome.  

PubMed

Cryopreservation is the only method for long-term storage of viable cells and tissues used for cellular therapy, stem cell transplantation and/or tissue engineering. However, the freeze-thaw process strongly contributes to cell and tissue damage through several mechanisms, including oxidative stress, cell injury from intracellular ice formation and altered physical cellular properties. Our previous proteomics investigation was carried out on Wharton's Jelly Stem Cells (WJSCs) having similar properties to adult mesenchymal stem cells and thus representing a rich source of primitive cells to be potentially used in regenerative medicine. The aim of the present work was to investigate molecular changes that occur in WJSCs proteome in different experimental conditions: fresh primary cell culture and frozen cell. To analyze changes in protein expression of WJSCs undergoing different culturing procedures, we performed a comparative proteomic analysis (2DE followed by MALDI-TOF MS/MS nanoESI-Q-TOF MS coupled with nanoLC) between WJSCs from fresh and frozen cell culturing, respectively. Frozen WJSCs showed qualitative and quantitative changes compared to cells from fresh preparation, expressing proteins involved in replication, cellular defence mechanism and metabolism, that could ensure freeze-thaw survival. The results of this study could play a key role in elucidating possible mechanisms related to maintaining active proliferation and maximal cellular plasticity and thus making the use of WJSCs in cell therapy safe following bio-banking. PMID:24619862

Di Giuseppe, F; Pierdomenico, L; Eleuterio, E; Sulpizio, M; Lanuti, P; Riviello, A; Bologna, G; Gesi, M; Di Ilio, C; Miscia, S; Marchisio, M; Angelucci, S

2014-06-01

30

Effect of dedifferentiation on time to mutation acquisition in stem cell-driven cancers.  

PubMed

Accumulating evidence suggests that many tumors have a hierarchical organization, with the bulk of the tumor composed of relatively differentiated short-lived progenitor cells that are maintained by a small population of undifferentiated long-lived cancer stem cells. It is unclear, however, whether cancer stem cells originate from normal stem cells or from dedifferentiated progenitor cells. To address this, we mathematically modeled the effect of dedifferentiation on carcinogenesis. We considered a hybrid stochastic-deterministic model of mutation accumulation in both stem cells and progenitors, including dedifferentiation of progenitor cells to a stem cell-like state. We performed exact computer simulations of the emergence of tumor subpopulations with two mutations, and we derived semi-analytical estimates for the waiting time distribution to fixation. Our results suggest that dedifferentiation may play an important role in carcinogenesis, depending on how stem cell homeostasis is maintained. If the stem cell population size is held strictly constant (due to all divisions being asymmetric), we found that dedifferentiation acts like a positive selective force in the stem cell population and thus speeds carcinogenesis. If the stem cell population size is allowed to vary stochastically with density-dependent reproduction rates (allowing both symmetric and asymmetric divisions), we found that dedifferentiation beyond a critical threshold leads to exponential growth of the stem cell population. Thus, dedifferentiation may play a crucial role, the common modeling assumption of constant stem cell population size may not be adequate, and further progress in understanding carcinogenesis demands a more detailed mechanistic understanding of stem cell homeostasis. PMID:24603301

Jilkine, Alexandra; Gutenkunst, Ryan N

2014-03-01

31

Effect of Dedifferentiation on Time to Mutation Acquisition in Stem Cell-Driven Cancers  

PubMed Central

Accumulating evidence suggests that many tumors have a hierarchical organization, with the bulk of the tumor composed of relatively differentiated short-lived progenitor cells that are maintained by a small population of undifferentiated long-lived cancer stem cells. It is unclear, however, whether cancer stem cells originate from normal stem cells or from dedifferentiated progenitor cells. To address this, we mathematically modeled the effect of dedifferentiation on carcinogenesis. We considered a hybrid stochastic-deterministic model of mutation accumulation in both stem cells and progenitors, including dedifferentiation of progenitor cells to a stem cell-like state. We performed exact computer simulations of the emergence of tumor subpopulations with two mutations, and we derived semi-analytical estimates for the waiting time distribution to fixation. Our results suggest that dedifferentiation may play an important role in carcinogenesis, depending on how stem cell homeostasis is maintained. If the stem cell population size is held strictly constant (due to all divisions being asymmetric), we found that dedifferentiation acts like a positive selective force in the stem cell population and thus speeds carcinogenesis. If the stem cell population size is allowed to vary stochastically with density-dependent reproduction rates (allowing both symmetric and asymmetric divisions), we found that dedifferentiation beyond a critical threshold leads to exponential growth of the stem cell population. Thus, dedifferentiation may play a crucial role, the common modeling assumption of constant stem cell population size may not be adequate, and further progress in understanding carcinogenesis demands a more detailed mechanistic understanding of stem cell homeostasis.

Jilkine, Alexandra; Gutenkunst, Ryan N.

2014-01-01

32

Hematopoietic stem cell donation.  

PubMed

Allogeneic hematopoietic stem cell transplantation is now an important treatment for numerous diseases. Donation of hematopoietic stem cells, either through bone marrow (BM) harvesting or peripheral blood stem cell (PBSC) collection, is a well-established and generally accepted procedure. The BM is aspirated from the posterior iliac crest under spinal or general anesthesia, and common side effects include fatigue and local pain. PBSC collection requires 4-6 days of G-CSF injections and leukapheresis 1-2 times. Common side effects of these procedures include bone pain, fatigue, and headache. The side effects of BM and PBSC collections are mostly transient and well tolerated. Severe adverse events are uncommon in healthy donors. At present, there is no definitive evidence to show that the stem cell donation increases the risk of marrow failure or cancer development. Nevertheless, all donors must be carefully evaluated and fully informed before donation. Donors must be able to provide informed consent without being coerced or pressured. Donors and graft products must be examined for potential agents to avoid transmitting infections and other diseases that may jeopardize donor's health during stem cell collection or recipient's well being after transplantation. Understanding the potential physical and psychological complications of stem cell donation and factors that may increase risks is very important to ensure that transplantation physicians maintain positive attitude in conducting this benevolent practice. PMID:23420184

Chen, Shu-Huey; Wang, Tso-Fu; Yang, Kuo-Liang

2013-04-01

33

Immunoregulatory effects of bone marrow-derived mesenchymal stem cells in the nasal polyp microenvironment.  

PubMed

Nasal polyposis is a severe, chronic inflammatory condition of the paranasal sinuses and is frequently associated with asthma and aspirin sensitivity. Mesenchymal stem cells exhibit a potent immunosuppressive effect in several inflammatory conditions, and their role in nasal polyposis remains little explored. Hence, we investigated whether bone marrow-derived mesenchymal stem cells could modulate cell phenotype in the nasal polyp milieu. After coculture with mesenchymal stem cells, the frequency of these inflammatory cells was found to decrease. Furthermore, mesenchymal stem cells promoted strong inhibition of CD4+ and CD8+ T cell proliferation, increased the frequency of CD4+CD25+Foxp3 T cells, and changed the global cytokine profile from an inflammatory to an anti-inflammatory response. We believe that mesenchymal stem cells may be a very useful adjunct for investigation of the inflammatory process in nasal polyposis, contributing to better understanding of the inflammatory course of this condition. PMID:24707116

Pezato, Rogério; de Almeida, Danilo Cândido; Bezerra, Thiago Freire; Silva, Fernando de Sá; Perez-Novo, Claudina; Gregório, Luís Carlos; Voegels, Richard Louis; Câmara, Niels Olsen; Bachert, Claus

2014-01-01

34

Immunoregulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in the Nasal Polyp Microenvironment  

PubMed Central

Nasal polyposis is a severe, chronic inflammatory condition of the paranasal sinuses and is frequently associated with asthma and aspirin sensitivity. Mesenchymal stem cells exhibit a potent immunosuppressive effect in several inflammatory conditions, and their role in nasal polyposis remains little explored. Hence, we investigated whether bone marrow-derived mesenchymal stem cells could modulate cell phenotype in the nasal polyp milieu. After coculture with mesenchymal stem cells, the frequency of these inflammatory cells was found to decrease. Furthermore, mesenchymal stem cells promoted strong inhibition of CD4+ and CD8+ T cell proliferation, increased the frequency of CD4+CD25+Foxp3 T cells, and changed the global cytokine profile from an inflammatory to an anti-inflammatory response. We believe that mesenchymal stem cells may be a very useful adjunct for investigation of the inflammatory process in nasal polyposis, contributing to better understanding of the inflammatory course of this condition.

Pezato, Rogerio; de Almeida, Danilo Candido; Bezerra, Thiago Freire; Silva, Fernando de Sa; Perez-Novo, Claudina; Gregorio, Luis Carlos; Voegels, Richard Louis; Camara, Niels Olsen; Bachert, Claus

2014-01-01

35

The opposite effects of Doxorubicin on bone marrow stem cells versus breast cancer stem cells depend on glucosylceramide synthase  

PubMed Central

Myelosuppression and drug resistance are common adverse effects in cancer patients with chemotherapy, and those severely limit the therapeutic efficacy and lead treatment failure. It is unclear by which cellular mechanism anticancer drugs suppress bone marrow, while drug-resistant tumors survive. We report that due to the difference of glucosylceramide synthase (GCS), catalyzing ceramide glycosylation, doxorubicin (Dox) eliminates bone marrow stem cells (BMSCs) and expands breast cancer stem cells (BCSCs). It was found that Dox decreased the numbers of BMSCs (ABCG2+) and the sphere formation in a dose-dependent fashion in isolated bone marrow cells. In tumor-bearing mice, Dox treatments (5 mg/kg, 6 days) decreased the numbers of BMSCs and white blood cells; conversely, those treatments increased the numbers of BCSCs (CD24?/CD44+/ESA+) more than threefold in the same mice. Furthermore, therapeutic-dose of Dox (1 mg/kg/week, 42 days) decreased the numbers of BMSCs while it increased BCSCs in vivo. Breast cancer cells, rather than bone marrow cells, highly expressed GCS, which was induced by Dox and correlated with BCSC pluripotency. These results indicate that Dox may have opposite effects, suppressing BMSCs versus expanding BCSCs, and GCS is one determinant of the differentiated responsiveness of bone marrow and cancer cells.

Bhinge, Kaustubh; Gupta, Vineet; Hosain, Salman; Satyanarayanajois, Seetharama D.; Meyer, Sharon A.; Blaylock, Benny; Zhang, Qian-Jin; Liu, Yong-Yu

2012-01-01

36

Stem cells in urology  

Microsoft Academic Search

The shortage of donors for organ transplantation has stimulated research on stem cells as a potential resource for cell-based therapy in all human tissues. Stem cells have been used for regenerative medicine applications in many organ systems, including the genitourinary system. The potential applications for stem cell therapy have, however, been restricted by the ethical issues associated with embryonic stem

Tamer Aboushwareb; Anthony Atala

2008-01-01

37

Combining Adult Stem Cells and Olfactory Ensheathing Cells: The Secretome Effect  

PubMed Central

Adipose-derived adult stem cells (ASCs), bone marrow mesenchymal stem cells (bmMSCs), and human umbilical cord perivascular cells (HUCPVCs) tissue have been widely tested for regenerative applications, such as bone regeneration. Moreover, olfactory ensheathing cells (OECs) show promise in promoting spinal cord injury (SCI) regeneration. Our group recently proposed the use of a hybrid scaffold targeting both vertebral bone repair and SCI regeneration. According to this concept, both MSCs and OECs should be in close contact to be influenced by the factors that are involved in secretion. For this reason, here we studied the effects of the OEC secretome on the metabolic activity and proliferation of ASCs, bmMSCs, and HUCPVCs. The stem cells' secretome effects on metabolic activity and proliferation of the OECs were also considered. In co-cultures of OECs with ASCs, bmMSCs, or HUCPVCs, the metabolic activity/viability, proliferation, and total cell numbers were measured after 2 and 7 days of culture. The results demonstrated that the secretome of OECs has a positive effect on the metabolic activity and proliferation of MSCs from different origins, especially on ASCs. Furthermore, in general, the stem cells' secretome also had a positive effect on the OECs behavior, particularly when ASCs were in co-culture with OECs. These results suggest that the most suitable combination of cells to be used in our hybrid scaffold is the OECs with the ASCs. Finally, this work adds new knowledge to the cell therapy field, bringing new information about paracrine interactions between OECs and distinct mesenchymal stems.

Silva, Nuno A.; Gimble, Jeffrey M.; Sousa, Nuno; Reis, Rui L.

2013-01-01

38

Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc  

Microsoft Academic Search

Intervertebral disc (IVD) degeneration, a common cause of low back pain in humans, is a relentlessly progressive phenomenon with no currently available effective treatment. In an attempt to solve this dilemma, we transplanted autologous mesenchymal stem cells (MSCs) from bone marrow into a rabbit model of disc degeneration to determine if stem cells could repair degenerated IVDs. LacZ expressing MSCs

Daisuke Sakai; Joji Mochida; Toru Iwashina; Akihiko Hiyama; Hiroko Omi; Masaaki Imai; Tomoko Nakai; Kiyoshi Ando; Tomomitsu Hotta

2006-01-01

39

Development of an invitro technique to use mouse embryonic stem cell in evaluating effects of xenobiotics  

EPA Science Inventory

Our goal has been to develop a high-throughput, in vitro technique for evaluating the effects of xenobiotics using mouse embryonic stem cells (mESCs). We began with the Embryonic Stem Cell Test (EST), which is used to predict the embryotoxic potential of a test compound by combin...

40

Tumor stem cells  

Microsoft Academic Search

Stem cells possess two basic characteristics: they are able to renew themselves and to develop into different cell types.\\u000a The link between normal stem cells and tumor cells could be examined in three aspects: what are the differences and similarities\\u000a in the control of self-renewal capacity between stem cells and tumor cells; whether tumor cells arise from stem cells; do

László Kopper; Melinda Hajdú

2004-01-01

41

Umbilical Cord Stem Cells  

Microsoft Academic Search

The two most basic properties of stem cells are the capacities to self-renew and to differentiate into multiple cell or tissue\\u000a types (1–3). Generally, stem cells are categorized as one of three types: embryonic stem cells (ES), embryonic germ cells (EG), or adult\\u000a stem cells. ES cells are derived from the inner cell mass of the blastula (Fig. 1). They

Kathy E. Mitchell

42

Mesenchymal stem cells protective effect in adriamycin model of nephropathy.  

PubMed

Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity. The in vivo experimental approach was carried out in male Sprague-Dawley rats (overall 60 animals) treated with different ADR schemes to induce acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of 1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but protected the kidney from severe glomerulosclerosis when given concomitantly to ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage. Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify proteinuria and progression to renal failure, which implies lack of regenerative potential in this model. PMID:19181210

Magnasco, Alberto; Corselli, Mirko; Bertelli, Roberta; Ibatici, Adalberto; Peresi, Monica; Gaggero, Gabriele; Cappiello, Valentina; Chiavarina, Barbara; Mattioli, Girolamo; Gusmano, Rosanna; Ravetti, Jean Louis; Frassoni, Francesco; Ghiggeri, Gian Marco

2008-01-01

43

Long-Lasting Inhibitory Effects of Fetal Liver Mesenchymal Stem Cells on T-Lymphocyte Proliferation  

Microsoft Academic Search

Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC

Massimo Giuliani; Maud Fleury; Amelia Vernochet; Farah Ketroussi; Denis Clay; Bruno Azzarone; Jean Jacques Lataillade; Antoine Durrbach

2011-01-01

44

The effect of nanofiber-guided cell alignment on the preferential differentiation of neural stem cells  

PubMed Central

Stem cells display sensitivity to substrate presentation of topographical cues via changes in cell morphology. These biomechanical responses may be transmitted to the nucleus through cytoskeletal-linked signaling pathways. Here we investigate the influence of aligned substratum topography on the cell morphology and subsequently, the neuronal differentiation capabilities of adult neural stem cells (ANSCs). ANSCs that were cultured on aligned fibers elongated along the major fiber axis. Upon induction of differentiation with retinoic acid, a higher fraction of cells on aligned fibers cells on aligned fibers exhibited markers of neuronal differentiation as compared with cells on random fiber or unpatterned surfaces. This effect was in part due to substrate selectivity, whereby aligned fiber substrates were less receptive to the attachment and continued survival of oligodendrocytes than random fiber or unpatterned substrates. Substrate-induced elongation alone was also effective in upregulating canonical Wnt signaling in ANSCs, which was further potentiated by retinoic acid treatment. These findings suggest a mechanism by which morphological controlof stem cells operates in concert with biochemical cues for cell fate determination.

Lim, Shawn H.; Liu, Xingyu Y.; Song, Hongjun; Yarema, Kevin J.; Mao, Hai-Quan

2011-01-01

45

The effect of stem cells in bridging peripheral nerve defects: a meta-analysis.  

PubMed

Object For decades the gold standard for reconstructing a large peripheral nerve defect has been, and remains, the nerve autograft. Alternatives to the nerve autograft include biological conduits and vessels. Adding stem cells in the lumen of a nerve conduit has been the subject of multiple studies. The purpose of the present meta-analysis was to summarize animal experimental studies on the effect of stem cells as a luminal additive when reconstructing a peripheral nerve defect with a nerve graft. Methods A literature search of the MEDLINE and Embase databases was performed from inception to April 2012, searching for animal experiments on peripheral nerve reconstruction models in which a nerve conduit was used with and without the support of 3 different types of stem cells. Stem cells were analyzed according to their origin: bone marrow, adipose tissue, and other origins. Included studies had consistent outcome measurements: walking track analysis, muscle mass ratio, and electrophysiology. Results Forty-four studies were included in the final analysis. Forest plots of the 3 outcome measurements (walking track analysis, muscle mass ratio, and electrophysiology) showed positive effects of stem cells on the regeneration of peripheral nerves at different time points. Almost all comparisons showed significant differences for all 3 stem cells groups compared with a control group in which stem cells were not used. Conclusions The present report systematically analyzed the different studies that used stem cells as a luminal additive when bridging a large peripheral nerve defect. All 3 different stem cell groups showed a beneficial effect when used in the reconstruction compared with control groups in which stem cells were not used. PMID:24816327

Hundepool, Caroline A; Nijhuis, Tim H J; Mohseny, Behnam; Selles, Ruud W; Hovius, Steven E R

2014-07-01

46

Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells.  

PubMed

Mesenchymal stem cells (MSCs) have profound immunomodulatory functions both in vitro and in vivo. However, their effects on the differentiation of dendritic cells (DCs) are unknown. In this study, we employed an in vitro model to investigate the effects of human MSCs on the development of DCs. CD34(+) cells isolated from cord blood were cultured under conventional DC(cDC) or plasmacytoid DC (pDC) differentiation conditions, in the presence or absence of MSCs or their conditioned medium. Here we show that both MSCs and their conditioned medium dramatically increased the numbers of cells generated under either condition. The percentage of cells with the cDC phenotype is significantly reduced in the presence of MSCs or their conditioned medium, whereas the percentage of pDC increased. The capacity of cDCs from MSCs or their conditioned medium-treated CD34(+) cells to stimulate allogeneic T cells was weakened. Furthermore, MSCs can skew the DC function from cDC to pDC, thus biasing the immune system toward Th2 and away from Th1 responses. Blocking the prostaglandin E(2) (PGE(2)) synthesis of MSCs can reverse most of these influences of MSCs on DCs differentiation and function. Therefore, MSCs can significantly influence DC development through PGE(2) production. PMID:17999594

Chen, Lei; Zhang, Wei; Yue, Han; Han, Qin; Chen, Bin; Shi, Mingxia; Li, Jing; Li, Binzong; You, Shengguo; Shi, Yufang; Zhao, Robert Chunhua

2007-10-01

47

The effect of bovine endosteum-derived particles on the proliferation of human mesenchymal stem cells.  

PubMed

There is a large biomanufacturing and clinical need for cost-effective and simple techniques to expand mesenchymal stem cells whilst retaining their multipotency. Endosteum-derived particles were prepared, characterised and examined as a biomaterial to facilitate the in vitro expansion of human mesenchymal stem cells. Bovine endosteum-derived particles are composed of chondroitin sulphate glycosaminoglycans with 4- and 6-sulphation and N-sulphated heparan sulphate glycosaminoglycans. The particles were positive for perlecan, laminin and fibronectin by immunohistochemistry and alpha-mannose, alpha-glucose, terminal N-acetyl-alpha-D-glucosamine, N-acetyl-alpha-galactosamine and alpha-fucose, using lectin binding. Human mesenchymal stem cells showed greater than 96% attachment to the particles after one day in spinner culture. After 7 days, the stem cells on decalcified particles were viable and had a 5-fold higher growth than the stem cells grown on Cytodex-2 beads. Significantly more stem cells were recovered from decalcified particles compared with mineralised particles (P < 0.05). Differentiation to chondrogenic, osteogenic and adipogenic lineages was maintained after culturing stem cells on the demineralised particles. We conclude that bovine endosteum-derived particles can be extracted from bone marrow to retain sulphated proteoglycans and glycosylated proteins. These particles are a suitable biomaterial for supporting the growth and retaining the multipotency of human mesenchymal stem cells. PMID:20434212

Nigro, Julie; White, Jacinta F; Ramshaw, John A M; Haylock, David N; Nilsson, Susan K; Werkmeister, Jerome A

2010-07-01

48

An Opposite Effect of the CDK Inhibitor, p18INK4c on Embryonic Stem Cells Compared with Tumor and Adult Stem Cells  

PubMed Central

Self-renewal is a feature common to both adult and embryonic stem (ES) cells, as well as tumor stem cells (TSCs). The cyclin-dependent kinase inhibitor, p18INK4c, is a known tumor suppressor that can inhibit self-renewal of tumor cells or adult stem cells. Here, we demonstrate an opposite effect of p18 on ES cells in comparison with teratoma cells. Our results unexpectedly showed that overexpression of p18 accelerated the growth of mouse ES cells and embryonic bodies (EB); on the contrary, inhibited the growth of late stage teratoma. Up-regulation of ES cell markers (i.e., Oct4, Nanog, Sox2, and Rex1) were detected in both ES and EB cells, while concomitant down-regulation of various differentiation markers was observed in EB cells. These results demonstrate that p18 has an opposite effect on ES cells as compared with tumor cells and adult stem cells. Mechanistically, expression of CDK4 was significantly increased with overexpression of p18 in ES cells, likely leading to a release of CDK2 from the inhibition by p21 and p27. As a result, self-renewal of ES cells was enhanced. Our current study suggests that targeting p18 in different cell types may yield different outcomes, thereby having implications for therapeutic manipulations of cell cycle machinery in stem cells.

Li, Yanxin; Pal, Rekha; Sung, Li-Ying; Feng, Haizhong; Miao, Weimin; Cheng, Shi-Yuan; Tian, Cindy; Cheng, Tao

2012-01-01

49

Effects of Polymer Surfaces on Proliferation and Differentiation of Embryonic Stem Cells and Bone Marrow Stem Cells  

NASA Astrophysics Data System (ADS)

Currently, proliferation and differentiation of stem cell is usually accomplished either in vivo, or on chemical coated tissue culture petri dish with the presence of feeder cells. Here we investigated whether they can be directly cultured on polymeric substrates, in the absence of additional factors. We found that mouse embryonic stem cells did not require gelatin and could remain in the undifferentiated state without feeder cells at least for four passages on partially sulfonated polystyrene. The modulii of cells was measured and found to be higher for cells plated directly on the polymer surface than for those on the same surface covered with gelatin and feeder cells. When plated with feeder cells, the modulii was not sensitive to gelatin. Whereas the differentiation properties of human bone marrow stem cells, which are not adherent, are less dependent on either chemical or mechanical properties of the substrate. However, they behave differently on different toughness hydrogels as oppose to on polymer coated thin films.

Qin, Sisi; Liao, Wenbin; Ma, Yupo; Simon, Marcia; Rafailovich, Miriam

2013-03-01

50

Hematopoietic Stem Cell Transplantation  

Microsoft Academic Search

\\u000a The purpose of hematopoietic stem cell transplantation (HSCT) is to replace diseased, damaged, or absent hematopoietic stem\\u000a cells (HSCs) with healthy HSCs. In general, allogeneic transplants are used when the hematopoietic stem cells are diseased\\u000a (e.g., leukemia), damaged (e.g., sickle cell disease), or absent (e.g., severe immunodeficiency disease). Autologous transplants\\u000a are used to provide stem cell rescue after higher doses

Robbie Norville; Deborah Tomlinson

51

Hair Follicle Stem Cells  

Microsoft Academic Search

The workshop on Hair Follicle Stem Cells brought together investigators who have used a variety of approaches to try to understand the biology of follicular epithelial stem cells, and the role that these cells play in regulating the hair cycle. One of the main concepts to emerge from this workshop is that follicular epithelial stem cells are multipotent, capable of

Robert M. Lavker; Tung-Tien Sun; Hideo Oshima; Yann Barrandon; Masashi Akiyama; Corinne Ferraris; Genevieve Chevalier; Bertrand Favier; Colin A. B. Jahoda; Danielle Dhouailly; Andrei A. Panteleyev; Angela M. Christiano

2003-01-01

52

The Influence of Microgravity on Astronaut Health: Global Study of Microgravity Effects on Human Stem Cells  

NASA Astrophysics Data System (ADS)

We employed here a global approach to examine the effect of microgravity on a stem cell line, and specific proteins were identified and linked to pathways that are affected by microgravity. This has significant implications to astronaut health.

Blaber, E.; Marcal, H.; Foster, L. J. R.; Burns, B. P.

2010-04-01

53

Stem Cells in Prostate.  

National Technical Information Service (NTIS)

This project aims to identify adult prostate stem cells, using tissue recombination techniques. To date, we have initiated studies utilizing mouse and human embryonic stem (ES) cells as outlined in the original statement of work. We have made progress tow...

G. Risbridger

2004-01-01

54

Comparative evaluation of the effects of statins on human stem and cancer cells in vitro.  

PubMed

Anticancer effects of statins were studied using karyotypically normal human embryonic stem cells (hESC) (HES3), karyotypically abnormal hESC (BG0IV), embryonal carcinoma (NTERA-2), ovarian (TOV-112D) and colorectal cancer (HT-29) cells. The cells were treated with simvastatin, pravastatin, mevastatin and lovastatin in vitro at different concentrations (1-20 mumol/l) and their effects on cell proliferation, apoptosis and stemness-related gene expression were studied. BG01V, NTERA-2 and TOV-112D contained duplications of chromosome 12 and 17. All four statins did not show any inhibition of HES3 proliferation. However, BG01V, NTERA-2, TOV-112D and HT-29 were inhibited by simvastatin, lovastatin and mevastatin. The inhibitory effects were reversed by farnesylpyrophosphate and geranylgeranylpyrophosphate. TUNEL and cell cycle assay revealed evidence of apoptosis in karyotypically abnormal cancer and stem cell types exposed to simvastatin and lovastatin. In addition, following simvastatin treatment, some of the apoptotic and stemness-related genes showed differential expression for the BG01V, NTERA-2, TOV-112D and HT-29 cells in comparison to HES3. In conclusion, the statins inhibit cell proliferation in karyotypically abnormal stem and cancer cells, probably via an increase in activity of key apoptotic genes and the suppression of stemness-related genes on chromosomes 12 and 17. PMID:18028750

Gauthaman, Kalamegam; Richards, Mark; Wong, John; Bongso, Ariff

2007-11-01

55

Hepatic stem cell niches  

PubMed Central

Stem cell niches are special microenvironments that maintain stem cells and control their behavior to ensure tissue homeostasis and regeneration throughout life. The liver has a high regenerative capacity that involves stem/progenitor cells when the proliferation of hepatocytes is impaired. In recent years progress has been made in the identification of potential hepatic stem cell niches. There is evidence that hepatic progenitor cells can originate from niches in the canals of Hering; in addition, the space of Disse may also serve as a stem cell niche during fetal hematopoiesis and constitute a niche for stellate cells in adults.

Kordes, Claus; Haussinger, Dieter

2013-01-01

56

Effective cryopreservation of human embryonic stem cells by the open pulled straw vitrification method  

Microsoft Academic Search

BACKGROUND: Human embryonic stem (ES) cells originate from the inner cell mass of the blastocyst, and retain in culture the properties of pluripotent cells of the early embryo. The study aim was to determine whether the open pulled straw (OPS) vitrification method, which is highly effective for the cryopreservation of embryos, might be also efficient for human ES cells. METHODS

B. E. Reubinoff; M. F. Pera; G. Vajta; A. O. Trounson

2001-01-01

57

Cancer stem cells - normal stem cells \\  

Microsoft Academic Search

Evidence has accumulated that cancer develops from a population of quiescent tissue committed\\/pluripotent stem cells (TCSC\\/PSC) or cells developmentally closely related to them that are distributed in various organs. To support this notio n, stem cells (SC) are long lived cells and thus may become the subject of accumulating mutations that are crucial for initiation\\/progression of cancer. More important, they

Mariusz Z. Ratajczak

2005-01-01

58

Stem Cell Biology  

Microsoft Academic Search

\\u000a Stem cells are functionally defined as long-lived cells that can both self-renew and differentiate into multiple cell types.\\u000a Embryonic stem cells, considered totipotent cells, give rise to all embryonic tissue layers and, consequently, all tissue\\u000a types. Hematologists\\/oncologists are perhaps most familiar with hematopoietic stem cells (HSCs): the single pluripotent cell\\u000a that can give rise to all lymphoid, myeloid and erythroid

Elizabeth O. Hexner; Stephen G. Emerson

59

Stem cells and neurodegenerative diseases.  

PubMed

Neurodegenerative diseases are characterized by the neurodegenerative changes or apoptosis of neurons involved in networks, which are important to specific physiological functions. With the development of old-aging society, the incidence of neurodegenerative diseases is on the increase. However, it is difficult to diagnose for most of neurodegenerative diseases. At present, there are too few effective therapies. Advances in stem cell biology have raised the hope and possibility for the therapy of neurodegenerative diseases. Recently, stem cells have been widely attempted to treat neurodegenerative diseases of animal model. Here we review the progress and prospects of various stem cells, including embryonic stem cells, mesenchymal stem cell and neural stem cells and so on, for the treatments of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Huntington' disease and Amyotrophic lateral sclerosis/Lou Gehrig's disease. PMID:18368305

Hou, LingLing; Hong, Tao

2008-04-01

60

Effects of EdU Labeling on Mesenchymal Stem Cells  

PubMed Central

Background Thymidine analog 5-ethynyl-2-deoxyuridine (EdU) has recently been employed for tracking mesenchymal stem cells (MSCs). In the present study we tested whether EdU was cytotoxic and whether it interfered with MSC’s differentiation, cytokine secretion, and migration. Methods EdU labeling was performed by incubating adipose-derived stem cells (ADSCs) with 10 ?M of EdU for 48 hours. Incorporation of EdU was detected by reaction with azide-conjugated Alexa594. The labeled and unlabeled ADSCs were compared for proliferation and apoptosis as determined by CellTiter and comet assays, respectively. They were also compared for neuron-like and endothelial differentiation as determined by morphology, marker expression, and function. Comparison of their secreted cytokine profile was performed by cytokine antibody array. Comparison of their response to homing factor SDF-1 was performed by migration assay. Results EdU was incorporated into the nucleus in approximately 70% of ADSCs. No significant differences in proliferation and apoptosis rates were observed between EdU-labeled and unlabeled ADSCs. Isobutylmethylxanthine (IBMX) induced both EdU-labeled and unlabeled ADSCs to assume a neuron-like morphology and to express ?-III tubulin. Endothelial growth medium-2 (EGM2) induced endothelial differentiation in both EdU-labeled and unlabeled ADSCs, including the ability to uptake low-density lipoprotein (LDL) and to form capillary-like structures as well as the expression of vWF, eNOS, and CD31. EdU-labeled and unlabeled ADSCs exhibited identical secreted cytokine profile and identical migratory response to SDF-1. Discussion At the recommended dosage of 10 ?M EdU is non-toxic to ADSCs. EdU label did not interfere with ADSC’s differentiation, cytokine secretion, or migratory response to SDF-1.

Ning, Hongxiu; Albersen, Maarten; Lin, Guiting; Lue, Tom F.; Lin, Ching-Shwun

2012-01-01

61

Comparing the immunoregulatory effects of stem cells from human exfoliated deciduous teeth and bone marrow-derived mesenchymal stem cells.  

PubMed

Stem cells from human exfoliated deciduous teeth (SHED) have been introduced recently and possess characteristics similar to mesenchymal stem cells (MSCs). Because of their convenient accessibility and safety of harvest, SHED can be a preferable source for the ever-increasing MSCs' applications  While they are new, their immunoproperties have not been adequately studied. In this study, we aimed to explore the effect of SHED on T lymphocytes and compare it to conventional MSCs (BMMSCs).At first the isolated T lymphocytes were activated specifically/nonspecifically in vitro and cocultured with SHED or BMMSCs under the same conditions, subsequently their proliferation and cytokine secretion (IL-2 and IFN-?) were measured.In our experiment, BMMSCs and SHED inhibit the proliferation and cytokine production of both PHA and alloantigen stimulated T lymphocytes in a dose-dependent manner. In direct and indirect contact to T lymphocytes, the inhibition of BMMSCs (but not of SHED) was significantly different The cytokine production from activated T cells was affected differently by two types of MSCs. The inhibition decreased by the separation of lymphocytes and MSCs by a semipermeable membrane, but it was not abolished.This study showed that SHED suppress the activation of human T lymphocytes in vitro like other MSCs. Compared to BMMSCs, this suppression was alleviated. In the equal conditions, the pattern of immune-modulation of BMMSCs and SHED was different, suggesting that SHED do not exert the exact mechanisms of BMMSCs' immunosuppression., This finding should be verified by further studies focused on the detailed mechanisms  of the immunomodulation of SHED and also BMMSCs. PMID:23996709

Alipour, Razieh; Adib, Minoo; Masoumi Karimi, Masoumeh; Hashemi-Beni, Batool; Sereshki, Nasrin

2013-12-01

62

Bystander effect-mediated gene therapy of gliomas using genetically engineered neural stem cells  

Microsoft Academic Search

Since neural stem cells (NSCs) have the ability to migrate toward a tumor mass, genetically engineered NSCs were used for the treatment of gliomas. We first evaluated the “bystander effect” between NSCs transduced with the herpes simplex virus-thymidine kinase (HSVtk) gene (NSCtk) and C6 rat glioma cells under both in vitro and in vivo conditions. A potent bystander effect was

Shaoyi Li; Tsutomu Tokuyama; Junkoh Yamamoto; Masayo Koide; Naoki Yokota; Hiroki Namba

2005-01-01

63

A review of the effects of the cell environment physicochemical nanoarchitecture on stem cell commitment.  

PubMed

Physicochemical features of a cell nanoenvironment exert important influence on stem cell behavior and include the influence of matrix elasticity and topography on differentiation processes. The presence of growth factors such as TGF-? and BMPs on these matrices provides chemical cues and thus plays vital role in directing eventual stem cell fate. Engineering of functional biomimetic scaffolds that present programmed spatio-temporal physical and chemical signals to stem cells holds great promise in stem cell therapy. Progress in this field requires tacit understanding of the mechanistic aspects of cell-environment nanointeractions, so that they can be manipulated and exploited for the design of sophisticated next generation biomaterials. In this review, we report and discuss the evolution of these processes and pathways in the context of matrix adhesion as they might relate to stemness and stem cell differentiation. Super-resolution microscopy and single-molecule methods for in vitro nano-manipulation are helping to identify and characterize the molecules and mechanics of structural transitions within stem cells and matrices. All these advances facilitate research toward understanding of stem cell niche and consequently to developing new class of biomaterials helping the "used biomaterials" for applications in tissue engineering and regenerative medicine. PMID:24720880

Das, Rajat K; Zouani, Omar F

2014-07-01

64

Optimizing stem cell culture.  

PubMed

Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. In the past few years, major efforts have been made to define more precisely the medium composition in which stem cells grow or differentiate. This led to the progressive replacement of ill-defined additives such as serum or feeder cell layers by recombinant cytokines or growth factors. Another example is the control of the oxygen pressure. For many years cell cultures have been done under atmospheric oxygen pressure which is much higher than the one experienced by stem cells in vivo. A consequence of cell metabolism is that cell culture conditions are constantly changing. Therefore, the development of high sensitive monitoring processes and control algorithms is required for ensuring cell culture medium homeostasis. Stem cells also sense the physical constraints of their microenvironment. Rigidity, stiffness, and geometry of the culture substrate influence stem cell fate. Hence, nanotopography is probably as important as medium formulation in the optimization of stem cell culture conditions. Recent advances include the development of synthetic bioinformative substrates designed at the micro- and nanoscale level. On going research in many different fields including stem cell biology, nanotechnology, and bioengineering suggest that our current way to culture cells in Petri dish or flasks will soon be outdated as flying across the Atlantic Ocean in the Lindbergh's plane. PMID:20803548

van der Sanden, Boudewijn; Dhobb, Mehdi; Berger, François; Wion, Didier

2010-11-01

65

Inhibitory effect and mechanism of mesenchymal stem cells on liver cancer cells.  

PubMed

Mesenchymal stem cells (MSCs), with their capacity for self-renewal and differentiation into various cell types, are important seed cells for stem cell therapy. MSCs exhibit potent pathotropic migratory properties that make them attractive for use in tumor prevention and therapy. However, little is known about the underlying molecular mechanisms that link MSCs to the targeted tumor cells. This study investigated the inhibitory effect and mechanism of MSCs on human hepatoma HepG2 cells using co-culture and conditioned medium system and animal transplantation model. The HepG2 cells were co-cultured with MSCs or treated with conditional media derived from MSCs cultures in vitro. Results of methylthiazolyldiphenyl tetrazolium assay and flow cytometric assay showed that the proliferation and apoptosis of HepG2 cells decreased and increased, respectively. Reverse transcription polymerase chain reaction analysis showed that the expression levels of bcl-2, c-Myc, ?-catenin, and survivin were downregulated. The results of enzyme-linked immunosorbent assay and Western blot proved that MSCs secreted Dkk-1 to inhibit the expression of Wnt signaling pathway-related factors (bcl-2, c-Myc, ?-catenin, and survivin) in tumor cells, consequently inhibiting the proliferation and promoting the apoptosis of HepG2 cells. Animal transplantation experiment showed that tumor growth was significantly inhibited when HepG2 cells were co-injected with MSCs into nude mice. These results suggested that MSCs inhibited the growth and promoted the apoptosis of HepG2 cells in a dose-dependent manner. This study provided a new approach and experimental basis for cancer therapy. This study also proved that the Wnt signaling pathway may have a function in MSC-mediated tumor cell inhibition. PMID:24136741

Hou, Lingling; Wang, Xiaoyu; Zhou, Yaqiong; Ma, Haibin; Wang, Ziling; He, Jinsheng; Hu, Honggang; Guan, Weijun; Ma, Yuehui

2014-02-01

66

Breast cancer stem cells  

Microsoft Academic Search

Since the initial discovery of leukemia stem cells nearly a decade ago, a great deal of cancer research has focused on the\\u000a identification of cancer stem cells (CSCs) in many types of solid tumors, including breast cancer. Through analysis of cell\\u000a surface markers and xenotransplant models, a subpopulation of putative human breast cancer stem cells (BCSCs) that is CD24-negative\\/CD44-positive\\u000a (CD24?\\/CD44+)

Kazuharu Kai; Yoshimi Arima; Toshio Kamiya; Hideyuki Saya

2010-01-01

67

Embryonic Stem Cells  

Microsoft Academic Search

Stem cells, which have a great capacity for self-renewal and can differentiate into at least one committed cell type, exist\\u000a in embryonic and adult organisms of many phyla. Although stem cells of various types from mice and other lower organisms have\\u000a been studied for many years, it was not until the derivation of stem cell lines from human embryos in

Victoria L. Browning; Jon S. Odorico

68

Mesenchymal stem cells  

Microsoft Academic Search

The tremendous capacity of bone to regenerate is indicative of the presence of stem cells with the capability, by definition,\\u000a to self-renew as well as to give rise to daughter cells. These primitive progenitors, termed mesenchymal stem cells or bone\\u000a marrow stromal stem cells, exist postnatally, and are multipotent with the ability to generate cartilage, bone, muscle, tendon,\\u000a ligament, and

Richard O. C. Oreffo; Cyrus Cooper; Christopher Mason; Mark Clements

2005-01-01

69

Brief Report: Parthenogenetic Embryonic Stem Cells are an Effective Cell Source for Therapeutic Liver Repopulation.  

PubMed

Parthenogenesis is the development of an oocyte without fertilization. Mammalian parthenogenetic (PG) embryos are not viable, but can develop into blastocysts from which embryonic stem cells (ESCs) have been derived in mouse and human. PG ESCs are frequently homozygous for alleles encoding major histocompatibility complex (MHC) molecules. MHC homozygosity permits much more efficient immune matching than MHC heterozygosity found in conventional ESCs, making PG ESCs a promising cell source for cell therapies requiring no or little immune suppression. However, findings of restricted differentiation and proliferation of PG cells in developmental chimeras have cast doubt on the potential of PG ESC derivatives for organ regeneration. To address this uncertainty, we determined whether PG ESC derivatives are effective in rescuing mice with lethal liver failure due to deficiency of fumarylacetoacetate hydrolase (Fah). In developmental chimeras generated by injecting wild-type PG ESCs into Fah-deficient blastocysts, PG ESCs differentiated into hepatocytes that could repopulate the liver, provide normal liver function, and facilitate long-term survival of adult mice. Moreover, after transplantation into adult Fah-deficient mice, PG ESC-derived hepatocytes efficiently engrafted and proliferated, leading to high-level liver repopulation. Our results show that-despite the absence of a paternal genome-PG ESCs can form therapeutically effective hepatocytes. Stem Cells 2014;32:1983-1988. PMID:24740448

Espejel, Silvia; Eckardt, Sigrid; Harbell, Jack; Roll, Garrett R; McLaughlin, K John; Willenbring, Holger

2014-07-01

70

Inhibitory effects of neural stem cells derived from human embryonic stem cells on differentiation and function of monocyte-derived dendritic cells.  

PubMed

Neural stem cells (NSCs) possess immunosuppressive characteristics, but effects of NSCs on human dendritic cells (DCs), the most important antigen presenting cells, are less well studied. We used an in vitro approach to evaluate the effects of human NSCs on differentiation of human blood CD14(+) monocytes into DCs. NSCs derived from H1 human embryonic stem cells (hESC-NSCs) and human ReNcell NSC line, as well as human bone marrow derived mesenchymal stem cells (MSCs), were tested. We observed that in response to treatment with interleukin-4 and granulocyte macrophage colony-stimulating factor CD14(+) monocytes co-cultured with NSCs were able to down-regulate CD14 and up-regulate the differentiation marker CD1a, whereas MSC co-culture strongly inhibited CD1a expression and supported prolonged expression of CD14. A similar difference between NSCs and MSCs was noted when lipopolysaccharides were included to induce maturation of monocyte-derived DCs. However, when effects on the function of derived DCs were investigated, NSCs suppressed the elevation of the DC maturation marker CD83, although not the up-regulation of costimulatory molecules CD80, CD86 and CD40, and impaired the functional capacity of the derived DCs to stimulate alloreactive T cells. We did not observe any obvious difference between hESC-NSCs and ReNcell NSCs in inhibiting DC maturation and function. Our data suggest that although human NSCs are less effective than human MSCs in suppressing monocyte differentiation into DCs, these stem cells can still affect the function of DCs, ultimately regulating specific immune responses. PMID:23664653

Shahbazi, Mohammad; Kwang, Timothy W X; Purwanti, Yovita Ida; Fan, Weimin; Wang, Shu

2013-07-15

71

The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis  

PubMed Central

This article examines the current use and future implications of stem cell therapy in treating Multiple Sclerosis (MS). MS is the most common neurological disease in young adults, affecting approximately two million people worldwide. Currently there is no cure for MS. The standard treatment of MS involves disease-modifying drugs, which work to alleviate the symptoms of MS. However, these drugs carry adverse side effects and are ineffective in preventing disease progression in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first used in 1995 to treat patients with severe rapidly progressing MS. The HSCT treatment protocol has evolved into a less intense conditioning regimen that is currently demonstrating efficacy in treating patients with variable disease severity—with best results in early-stage rapidly progressing MS patients with active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental stem cell therapy currently undergoing clinical trials. Animal models and early clinical trials have shown promise that MSCT might be a low risk treatment to precipitate neuroregeneration and immunomodulation in MS patients. Specifically, neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial therapeutic approach, holds promise for a better treatment for MS.

Holloman, Jameson P; Ho, Calvin C; Hukki, Arushi; Huntley, Jennifer L; Gallicano, G Ian

2013-01-01

72

Stem cells and reproduction  

PubMed Central

Purpose of review To review the latest developments in reproductive tract stem cell biology. Recent findings In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cyropreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. Summary Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent.

Du, Hongling; Taylor, Hugh S.

2011-01-01

73

Optimizing stem cell culture  

PubMed Central

Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. This led to the progressive replacement of ill-defined additives such as serum or feeder cell layers by recombinant cytokines or growth factors. Another example is the control of the oxygen pressure. For many years cell cultures have been done under atmospheric oxygen pressure which is much higher than the one experienced by stem cells in vivo. A consequence of cell metabolism is that cell culture conditions are constantly changing. Therefore, the development of high sensitive monitoring processes and control algorithms is required for ensuring cell culture medium homeostasis. Stem cells also sense the physical constraints of their microenvironment. Rigidity, stiffness and geometry of the culture substrate influence stem cell fate. Hence, nanotopography is probably as important as medium formulation in the optimization of stem cell culture conditions. Recent advances include the development of synthetic bioinformative substrates designed at the micro- and nanoscale level. On going research in many different fields including stem cell biology, nanotechnology, and bioengineering suggest that our current way to culture cells in Petri dish or flasks will soon be outdated as flying across the Atlantic Ocean in the Lindbergh’s plane.

Van Der Sanden, Boudewijn; Dhobb, Mehdi; Berger, Francois; Wion, Didier

2010-01-01

74

Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.  

PubMed

The mechanism for stem cell-mediated improvement following acute myocardial infarction has been actively debated. We support hypotheses that the stem cell effect is primarily paracrine factor-linked. We used a heparin-presenting injectable nanofibre network to bind and deliver paracrine factors derived from hypoxic conditioned stem cell media to mimic this stem cell paracrine effect. Our self-assembling peptide nanofibres presenting heparin were capable of binding paracrine factors from a medium phase. When these factor-loaded materials were injected into the heart following coronary artery ligation in a mouse ischaemia-reperfusion model of acute myocardial infarction, we found significant preservation of haemodynamic function. Through media manipulation, we were able to determine that crucial factors are primarily < 30 kDa and primarily heparin-binding. Using recombinant VEGF- and bFGF-loaded nanofibre networks, the effect observed with conditioned media was recapitulated. When evaluated in another disease model, a chronic rat ischaemic hind limb, our factor-loaded materials contributed to extensive limb revascularization. These experiments demonstrate the potency of the paracrine effect associated with stem cell therapies and the potential of a biomaterial to bind and deliver these factors, pointing to a potential therapy based on synthetic materials and recombinant factors as an acellular therapy. PMID:20222010

Webber, Matthew J; Han, Xiaoqiang; Murthy, S N Prasanna; Rajangam, Kanya; Stupp, Samuel I; Lomasney, Jon W

2010-12-01

75

Effects of engrafted neural stem cells derived from GFP transgenic mice in Parkinson's diseases rats  

Microsoft Academic Search

This study evaluated the therapeutic effect of neural stem cells (NSCs) transplanted into Parkinson's disease (PD) rats. NSCs were identified in vitro, then engrafted into the striatum of the PD rats. The rotational behavior was evaluated 1, 2, 4 and 6 weeks. A significant rotational behavior improvement was observed in PD rats subjected to cell transplantation. Transplanted NSCs not only

Peng Wei; Jia Liu; Hao-Li Zhou; Zhi-Tong Han; Qing-Ying Wu; Jiang-Xia Pang; Su Liu; Ting-Hua Wang

2007-01-01

76

Mesenchymal stem cell secreted platelet derived growth factor exerts a pro-migratory effect on resident Cardiac Atrial appendage Stem Cells.  

PubMed

Mesenchymal stem cells (MSCs) modulate cardiac healing after myocardial injury through the release of paracrine factors, but the exact mechanisms are still unknown. One possible mechanism is through mobilization of endogenous cardiac stem cells (CSCs). This study aimed to test the pro-migratory effect of MSC conditioned medium (MSC-CM) on endogenous CSCs from human cardiac tissue. By using a three-dimensional collagen assay, we found that MSC-CM improved migration of cells from human cardiac tissue. Cell counts, perimeter and area measurements were utilized to quantify migration effects. To examine whether resident stem cells were among the migrating cells, specific stem cell properties were investigated. The migrating cells displayed strong similarities with resident Cardiac Atrial appendage Stem Cells (CASCs), including a clonogenic potential of ~21.5% and expression of pluripotency associated genes like Oct-4, Nanog, c-Myc and Klf-4. Similar to CASCs, migrating cells demonstrated high aldehyde dehydrogenase activity and were able to differentiate towards cardiomyocytes. Receptor tyrosine kinase analysis and collagen assays performed with recombinant platelet derived growth factor (PDGF)-AA and Imatinib Mesylate, a PDGF receptor inhibitor, suggested a role for the PDGF-AA/PDGF receptor ? axis in enhancing the migration process of CASCs. In conclusion, our findings demonstrate that factors present in MSC-CM improve migration of resident stem cells from human cardiac tissue. These data open doors towards future therapies in which MSC secreted factors, like PDGF-AA, can be utilized to enhance the recruitment of CASCs towards the site of myocardial injury. PMID:24326234

Windmolders, Severina; De Boeck, Astrid; Koninckx, Remco; Daniëls, Annick; De Wever, Olivier; Bracke, Marc; Hendrikx, Marc; Hensen, Karen; Rummens, Jean-Luc

2014-01-01

77

Effects of hyperthermia and radiation on mouse testis stem cells  

SciTech Connect

The response of mouse testis stem cells to hyperthermia and combined hyperthermia-radiation treatments was assayed by spermatogenic colony regrowth, sperm head counts, testis weight loss, and fertility. With the use of spermatogenic colony assay, thermal enhancement ratios at an isosurvival level of 0.1 were 1.27 at 41 degrees, 1.80 at 42 degrees, and 3.97 at 43 degrees for testes exposed to heat for 30 min prior to irradiation. Sperm head counts were reduced by heat alone from a surviving fraction of 0.58 at 41 degrees to 0.003 at 42.5-43.5 degrees. Curves for sperm head survival measured 56 days after the testes had been heated for 30 min prior to irradiation were biphasic and showed a progressive downward displacement to lower survival with increasing temperature. The 41, 42, and 43 degrees curves were displaced downward by factors of 2, 58, and 175, respectively. The proportion of animals remaining sterile after 30 min of heat (41-43 degrees) and the median sterility period in days increased with increasing temperature. The minimum sperm count necessary to regain fertility was 13% of the normal mouse level.

Reid, B.O.; Mason, K.A.; Withers, H.R.; West, J.

1981-11-01

78

Stem Cell Resources  

NSDL National Science Digital Library

The mission of the Stem Cell Resources website is "to provide timely, reliable, high-quality and scientifically credible stem cell information for the educational community worldwide." The website is a division of Bioscience Network which publishes online science education materials. On the site, visitors will find a stem cell image library, a multimedia area, and a special section titled "For Educators". In the "For Educators" area, visitors will find links to a primer on stem cells and links to educational resources on stem cells from curriculum to case studies to lesson plans from such trusted sources as the Australian Stem Cell Centre and the National Institutes of Health. Moving on, the "Multimedia" area includes videos that show how embryonic stem cell lines are made, along with other animations and graphics on the topic. Additionally, the site's "SCR Library" area includes the link to the Stem Cell Image Library, which provides dozens of photos of stem cells taken from researchers at the University of Cambridge and other institutions.

79

Hair follicle stem cells  

Microsoft Academic Search

The increasing use of the hair follicle as a stem cell paradigm is due in part to the complex interplay between epithelial, dermal and other cell types, each with interesting differentiation potential and prospective therapeutic applications. This review focuses on research into the environmental niche, gene expression profiles and plasticity of hair follicle stem cell populations, where many recent advances

James M. Waters; Gavin D. Richardson; Colin A. B. Jahoda

2007-01-01

80

Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells  

SciTech Connect

Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as {beta}-myosin heavy chain ({beta}-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.

Nakanishi, Chiaki [Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565 (Japan); Division of Cardiovascular Medicine, Kanazawa University, Graduate School of Medicine, Kanazawa (Japan); Yamagishi, Masakazu [Division of Cardiovascular Medicine, Kanazawa University, Graduate School of Medicine, Kanazawa (Japan); Yamahara, Kenichi [Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565 (Japan); Hagino, Ikuo [Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka (Japan); Mori, Hidezo [Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Osaka (Japan); Sawa, Yoshiki [Department of Surgery, Osaka University Graduate School of Medicine, Osaka (Japan); Yagihara, Toshikatsu; Kitamura, Soichiro [Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka (Japan); Nagaya, Noritoshi [Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565 (Japan)], E-mail: myamagi@med.kanazawa-u.ac.jp

2008-09-12

81

Stem cell therapies for the treatment of radiation-induced normal tissue side effects.  

PubMed

Abstract Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for restoring functionality to the irradiated tissue bed. Recent Advances: Preclinical studies presented in this review provide encouraging proof of concept regarding the therapeutic potential of stem cells for treating the adverse side effects associated with radiotherapy in different organs. Early-stage clinical data for radiation-induced lung, bone, and skin complications are promising and highlight the importance of selecting the appropriate stem cell type to stimulate tissue regeneration. Critical Issues: While therapeutic efficacy has been demonstrated in a variety of animal models and human trials, a range of additional concerns regarding stem cell transplantation for ameliorating radiation-induced normal tissue sequelae remain. Safety issues regarding teratoma formation, disease progression, and genomic stability along with technical issues impacting disease targeting, immunorejection, and clinical scale-up are factors bearing on the eventual translation of stem cell therapies into routine clinical practice. Future Directions: Follow-up studies will need to identify the best possible stem cell types for the treatment of early and late radiation-induced normal tissue injury. Additional work should seek to optimize cellular dosing regimes, identify the best routes of administration, elucidate optimal transplantation windows for introducing cells into more receptive host tissues, and improve immune tolerance for longer-term engrafted cell survival into the irradiated microenvironment. Antioxid. Redox Signal. 21: 338-355. PMID:24147585

Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Luijk, Peter Van; Limoli, Charles L

2014-07-10

82

Stem cell therapy for osteoporosis.  

PubMed

Osteoporosis is a debilitating disease that affects millions of people worldwide. Current osteoporosis treatments are predominantly bone-resorbing drugs that are associated with several side effects. The use of stem cells for tissue regeneration has raised great hope in various fields of medicine, including musculoskeletal disorders. Stem cell therapy for osteoporosis could potentially reduce the susceptibility of fractures and augment lost mineral density by either increasing the numbers or restoring the function of resident stem cells that can proliferate and differentiate into bone-forming cells. Such osteoporosis therapies can be carried out by exogenous introduction of mesenchymal stem cells (MSCs), typically procured from bone marrow, adipose, and umbilical cord blood tissues or through treatments with drugs or small molecules that recruit endogenous stem cells to osteoporotic sites. The main hurdle with cell-based osteoporosis therapy is the uncertainty of stem cell fate and biodistribution following cell transplantation. Therefore, future advancements will focus on long-term engraftment and differentiation of stem cells at desired bone sites for tangible clinical outcome. PMID:24407712

Antebi, Ben; Pelled, Gadi; Gazit, Dan

2014-03-01

83

Stem Cell Separation Technologies.  

PubMed

Stem cell therapy and translational stem cell research require large-scale supply of stem cells at high purity and viability, thus leading to the development of stem cell separation technologies. This review covers key technologies being applied to stem cell separation, and also highlights exciting new approaches in this field. First, we will cover conventional separation methods that are commercially available and have been widely adapted. These methods include Fluorescence-activated cell sorting (FACS), Magnet-activated cell sorting (MACS), pre-plating, conditioned expansion media, density gradient centrifugation, field flow fractionation (FFF), and dielectrophoresis (DEP). Next, we will introduce emerging novel methods that are currently under development. These methods include improved aqueous two-phase system, systematic evolution of ligands by exponential enrichment (SELEX), and various types of microfluidic platforms. Finally, we will discuss the challenges and directions towards future breakthroughs for stem cell isolation. Advancing stem cell separation techniques will be essential for clinical and research applications of stem cells. PMID:23505616

Zhu, Beili; Murthy, Shashi K

2013-02-01

84

Stem cell therapy without the cells  

PubMed Central

As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells1 instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.2 We most often think of stem cell therapy acting to regenerate tissue through replication and then differentiation, but recent studies point to the dramatic effects adult stem cells exert in the repair of various tissues through the release of paracrine and autocrine substances, and not simply through differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells has been shown to be through paracrine mediated actions.3 That is, the collected types of molecules released by the stem cells, called the secretome, or stem cell released molecules (SRM), number in the 100s, including proteins, microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a multitude of biological pathways through paracrine actions. The composition of the different molecule types in SRM is state dependent, and varies with cell type and conditions such as age and environment.

Maguire, Greg

2013-01-01

85

Stem cell therapy without the cells.  

PubMed

As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells(1) instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.(2) We most often think of stem cell therapy acting to regenerate tissue through replication and then differentiation, but recent studies point to the dramatic effects adult stem cells exert in the repair of various tissues through the release of paracrine and autocrine substances, and not simply through differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells has been shown to be through paracrine mediated actions.(3) That is, the collected types of molecules released by the stem cells, called the secretome, or stem cell released molecules (SRM), number in the 100s, including proteins, microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a multitude of biological pathways through paracrine actions. The composition of the different molecule types in SRM is state dependent, and varies with cell type and conditions such as age and environment. PMID:24567776

Maguire, Greg

2013-11-01

86

STEM CELLS, CELL TRANSPLANTATION AND LIVER REPOPULATION  

PubMed Central

Liver transplantation is currently the only therapeutic option for patients with end-stage chronic liver disease and for severe acute liver failure. Because of limited donor availability, attention has been focused on the possibility to restore liver mass and function through cell transplantation. Stem cells are a promising source for liver repopulation after cell transplantation, but whether or not the adult mammalian liver contains hepatic stem cells is highly controversial. Part of the problem is that proliferation of mature adult hepatocytes is sufficient to regenerate the liver after two-thirds partial hepatectomy or acute toxic liver injury and participation of stem cells is not required. However, under conditions in which hepatocyte proliferation is blocked, undifferentiated epithelial cells in the periportal areas, called “oval cells”, proliferate, differentiate into hepatocytes and restore liver mass. These cells are referred to as facultative liver stem cells, but they do not repopulate the normal liver after their transplantation. In contrast, epithelial cells isolated from the early fetal liver can effectively repopulate the normal liver, but they are already traversing the hepatic lineage and may not be true stem cells. Mesenchymal stem cells and embryonic stem cells can be induced to differentiate along the hepatic lineage in culture, but at present these cells are inefficient in repopulating the liver. This review will characterize these various cell types and compare the properties of these cells and the conditions under which they do or do not repopulate the liver following their transplantation.

Oertel, Michael; Shafritz, David A.

2008-01-01

87

Stem Cell Transplantation for Neuroprotection in Stroke  

PubMed Central

Stem cell-based therapies for stroke have expanded substantially over the last decade. The diversity of embryonic and adult tissue sources provides researchers with the ability to harvest an ample supply of stem cells. However, the optimal conditions of stem cell use are still being determined. Along this line of the need for optimization studies, we discuss studies that demonstrate effective dose, timing, and route of stem cells. We recognize that stem cell derivations also provide uniquely individual difficulties and limitations in their therapeutic applications. This review will outline the current knowledge, including benefits and challenges, of the many current sources of stem cells for stroke therapy.

Shinozuka, Kazutaka; Dailey, Travis; Tajiri, Naoki; Ishikawa, Hiroto; Kaneko, Yuji; Borlongan, Cesar V.

2013-01-01

88

Stem cells and progenitor cells in renal disease  

Microsoft Academic Search

Stem cells and progenitor cells in renal tissue. Stem cells and progenitor cells are necessary for repair and regeneration of injured renal tissue. Infiltrating or resident stem cells can contribute to the replacement of lost or damaged tissue. However, the regulation of circulating progenitor cells is not well understood. We have analyzed the effects of erythropoietin on circulating progenitor cells

HERMANN HALLER; KIRSTEN DE GROOT; FERDINAND BAHLMANN; MARLIES ELGER; DANILO FLISER

2005-01-01

89

Stem cells in dermatology*  

PubMed Central

Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.

Ogliari, Karolyn Sassi; Marinowic, Daniel; Brum, Dario Eduardo; Loth, Fabrizio

2014-01-01

90

Pluripotent stem cells  

Microsoft Academic Search

The isolation of human embryonic stem cells (ESC) in 1998 has created the hope that stem cells will one day be used to regenerate tissues and organs, even though it is obvious that a number of hurdles will need to be overcome for such therapies to become reality. The cloning of “Dolly” in 1997, more than 40 years after the first

C. Verfaillie

2009-01-01

91

Mammary Stem Cell Isolation.  

National Technical Information Service (NTIS)

The objective of this research was to identify mouse mammary gland stem cells, with the ultimate goal being their isolation. We hypothesized that mammary gland stem cells can be identified by generating transgenic mice using a LEF/TCF-dependent reporter g...

D. J. Sussman

2004-01-01

92

Synergistic effects of combining adult neural stem cells with mesenchymal stem cells as a transplant therapy in the transgenic rat model of Huntington's disease  

Microsoft Academic Search

Huntington's disease (HD) is a progressive neurodegenerative disease that is marked by choreic movements and a decline in cognitive abilities. Adult stem cells such as adult neural stem cells (ANSCs) and mesenchymal stem cells (MSCs) exhibit the ability to differentiate into neural lineages representing an attractive source for cell replacement therapy in neurological disorders, such as HD. ANSCs have been

J. ROSSIGNOL; K. K. DAVIS; S. C. CLERC; S. A. LOWRANCE; J. J. MATCHYNSKI; M. C. BOMBARD; K. D. FINK; K. RABER; S. VON HÖRSTEN; L. LESCAUDRON; G. L. DUNBAR

93

Stem Cell Differentiation Game  

NSDL National Science Digital Library

This game uses a modified Uno deck to review concepts related to stem cell research and diabetes. Specifically, it covers material in the "Pulse-Chase Primer," "Pancreatic Beta Cells," and "Microarrays and Stem Cells" activities from the same resource which may or may not be necessary to complete prior to this activity (depending on learner's prior knowledge). Learners accumulate points and answer questions about stem cells, development, and microarrays so that they can be the first to differentiate into a pancreatic beta (β) cell. This activity is recommended for learners studying Biology at the High School (honors, IB and AP) or Undergraduate level.

Colvard, Mary

2010-01-01

94

Histological Experimental Study on the Effect of Stem Cell Therapy on Adriamycin Induced Chemobrain  

PubMed Central

Background and Objectives: Negative consequences of chemotherapy on brain function were suggested and were addressed in animal models as the clinical phenomenon of chemobrain .It was postulated that adriamycin (ADR) induce changes in behaviour and in brain morphology. Human umbilical cord mesenchymal stem cells (HUCMSCs) could be induced to differentiate into neuron-like cells .The present study aimed at investigating the possible therapeutic effect of HUCMSC therapy on adriamycin induced chemobrain in rat. Methods and Results: Twenty five female albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg ADR. The rats were sacrificed two and four weeks following confirmation of brain damage. In stem cell therapy group, rats were injected with HUCMSCs following confirmation of brain damage and sacrificed two and four weeks after therapy. Brain sections were exposed to histological, histochemical, immunohistochemical and morphometric studies. In ADR group, multiple shrunken neurons exhibiting dark nuclei and surrounded by vacuoles were seen .In response to SC therapy ,multiple normal pyramidal nerve cells were noted. The area of shrunken nerve cells exhibiting dark nuclei, Prussion blue and CD105 positive cells were significantly different in ADR group in comparison to SC therapy group. Conclusions: ADR induced progressive duration dependant cerebral degenerative changes. These changes were ameliorated following cord blood human mesenchymal stem cell therapy. A reciprocal relation was recorded between the extent of regeneration and the existence of undifferentiated mesenchymal stem cells.

El Aziz, Dalia Hussein Abd; Metwally, Hala Gabr

2013-01-01

95

Effect of avidin-like proteins and biotin modification on mesenchymal stem cell adhesion  

PubMed Central

The avidin-biotin system is a highly specific reaction that has been used in a wide range of biomedical applications, including surface modification and cell patterning. We systematically examined a number of avidin derivatives as the basis for a simple and cost effective tissue culture polystyrene substrate surface modification for human stem cell culture. Non-specific adhesion between human mesenchymal stem cells and various avidin derivatives, media conditions, and subsequent biotinylation reactions was quantified. We observed significant non-specific cell adhesion to avidin and strepthavidin, indicating that previous observations using this system may be artifactual. Seeding of cells in serum free media, blocking with bovine-serum albumin, and the use of the avidin derivative Neutravidin were all necessary for elimination of background adhesion. Neutravidin conjugated with biotinylated bsp-RGD(15) peptide provided the most robust cell adhesion, as well as the greatest increase in cell adhesion over background levels.

Schmidt, Ray C.; Healy, Kevin E.

2013-01-01

96

The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells  

Microsoft Academic Search

Developing effective drug therapies for arrhythmic diseases is hampered by the fact that the same drug can work well in some individuals but not in others. Human induced pluripotent stem (iPS) cells have been vetted as useful tools for drug screening. However, cardioactive drugs have not been shown to have the same effects on iPS cell-derived human cardiomyocytes as on

Noritaka Yokoo; Shiro Baba; Shinji Kaichi; Akira Niwa; Takahiro Mima; Hiraku Doi; Shinya Yamanaka; Tatsutoshi Nakahata; Toshio Heike

2009-01-01

97

Senescence effects of Angelica sinensis polysaccharides on human acute myelogenous leukemia stem and progenitor cells.  

PubMed

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML CD34+CD38? cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched CD34+CD38? cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML CD34+CD38? cells but not those from normal CD34+CD38? cells. Examination of the underlying mechanisms revealed that ASP induced CD34+CD38? cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy. PMID:24377566

Liu, Jun; Xu, Chun-Yan; Cai, Shi-Zhong; Zhou, Yue; Li, Jing; Jiang, Rong; Wang, Ya-Ping

2013-01-01

98

Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study  

PubMed Central

Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-? (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-? following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.

Moodley, Yuben; Vaghjiani, Vijesh; Chan, James; Baltic, Svetlana; Ryan, Marisa; Tchongue, Jorge; Samuel, Chrishan S.; Murthi, Padma; Parolini, Ornella; Manuelpillai, Ursula

2013-01-01

99

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells.  

PubMed

Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ?40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk. PMID:24753613

Kilcoyne, Karen R; Smith, Lee B; Atanassova, Nina; Macpherson, Sheila; McKinnell, Chris; van den Driesche, Sander; Jobling, Matthew S; Chambers, Thomas J G; De Gendt, Karel; Verhoeven, Guido; O'Hara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathália L M; Anderson, Richard A; Sharpe, Richard M

2014-05-01

100

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells  

PubMed Central

Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ?40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk.

Kilcoyne, Karen R.; Smith, Lee B.; Atanassova, Nina; Macpherson, Sheila; McKinnell, Chris; van den Driesche, Sander; Jobling, Matthew S.; Chambers, Thomas J. G.; De Gendt, Karel; Verhoeven, Guido; O'Hara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathalia L. M.; Anderson, Richard A.; Sharpe, Richard M.

2014-01-01

101

Imatinib has deleterious effects on differentiating spermatogonia while sparing spermatogonial stem cell self renewal  

PubMed Central

Imatinib mesylate is among a growing number of effective cancer drugs that provide molecularly targeted therapy; however, imatinib causes reproductive defects in rodents. The availability of an in vitro system for screening the effect of drugs on spermatogenesis would be beneficial. The imatinib targets, KIT and platelet-derived growth factor receptor beta (PDGFRB), were shown here to be expressed in “germline stem” (GS) cell cultures that contain spermatogonia, including spermatogonial stem cells (SSCs). GS cell cultures were utilized to determine whether imatinib affects SSC self renewal or differentiation. GS cells grown in imatinib retained self renewal based on multiple assays, including transplantation. However, growth in imatinib led to decreased numbers of differentiated spermatogonia and reduced culture growth consistent with the known requirement for KIT in survival and proliferation of spermatogonia. These results build upon the in vivo studies and support the possibility of utilizing GS cell cultures for preclinical drug tests.

Heim, Crystal; Minniear, Kayla; Dann, Christina Tenenhaus

2011-01-01

102

Effects of oxytocin on cardiomyocyte differentiation from mouse embryonic stem cells  

Microsoft Academic Search

This study sought to investigate the presence of oxytocin receptors and the possible biological role of oxytocin as an effective factor in the differentiation of embryonic stem cells (ESCs) into cardiomyocytes. Mouse ESCs were cultivated in hanging drops to form embryoid bodies (EBs). The EBs were then treated with and without oxytocin (experimental and control groups). Up to 30 days after

Leili Hatami; Mojtaba Rezazadeh Valojerdi; Seyed Javad Mowla

2007-01-01

103

Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: an update  

Microsoft Academic Search

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for various malignant and non-malignant diseases. Many patients have now been followed for two or three decades posttransplant and are presumed to be cured. With the tremendous advances achieved in terms of supportive care, it is reasonable to expect outcomes to improve steadily and consequently increasing numbers of transplant survivors

B Mohty; M Mohty

2011-01-01

104

Effect of complete response on outcome following autologous stem cell transplantation for myeloma  

Microsoft Academic Search

We studied the effect of complete response (CR) among 126 consecutive patients who underwent stem cell transplantation (SCT) for myeloma. The CR rate with SCT was 33%. Median overall survival (OS) from diagnosis of myeloma was 56 months. OS following SCT was 22 months. Progression-free survival (PFS) was 12 months. OS was not different between patients who achieved CR and

SV Rajkumar; R Fonseca; A Dispenzieri; MQ Lacy; TE Witzig; JA Lust; D Larson; TM Therneau; RA Kyle; PR Greipp; MA Gertz

2000-01-01

105

Prostate cancer stem cells  

PubMed Central

Despite the discovery over 60 years ago by Huggins and Hodges 1 that prostate cancers respond to androgen deprivation therapy, hormone-refractory prostate cancer remains a major clinical challenge. There is now mounting evidence that solid tumours originate from undifferentiated stem cell-like cells coexisting within a heterogeneous tumour mass that drive tumour formation, maintain tumour homeostasis and initiate metastases. This review focuses upon current evidence for prostate cancer stem cells, addressing the identification and properties of both normal and transformed prostate stem cells.

Lang, SH; Frame, FM; Collins, AT

2009-01-01

106

Autophagy in stem cells  

PubMed Central

Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future.

Guan, Jun-Lin; Simon, Anna Katharina; Prescott, Mark; Menendez, Javier A.; Liu, Fei; Wang, Fen; Wang, Chenran; Wolvetang, Ernst; Vazquez-Martin, Alejandro; Zhang, Jue

2013-01-01

107

Effects of extracellular matrices on F9 teratocarcinoma stem cells: a crucial role of type IV collagen in the early stage of differentiation of F9 stem cells.  

PubMed

F9 teratocarcinoma stem cells treated with retinoic acid (RA) differentiate into visceral endoderm, and this process affects the expression of some extracellular matrix (ECM) proteins. As the direct influence of ECM molecules on the differentiation of F9 stem cells has not been studied, we investigated the effects of various ECM proteins on the early differentiation of these cells. Monolayers of F9 stem cells were cultured on dishes coated with various ECM, such as type I or IV collagen, fibronectin, or laminin. They aggregated and formed spheroid bodies in the absence of RA only on type IV collagen. The outer layer cells of the spheroid bodies exhibited numerous microvilli, junctional complexes and mature cell organelles. Alpha-fetoprotein was positive in the outer layer cells. A small amount of laminin was detected in the matrix of the spheroid bodies. These data suggest that type IV collagen promoted the early stage of the differentiation of F9 stem cells without RA. The other ECM molecules failed to induce them to form spheroid bodies. The reversibility of the structure of the spheroid bodies to a monolayer was also examined. When the spheroid bodies were reseeded only on fibronectin- or laminin-coated culture dishes, they broke down and the cells spread to the surface in the absence of RA. The differentiation of F9 stem cells induced by type IV collagen seemed to be reversible and to take place at an early stage of their morphogenesis. These findings suggest that type IV collagen plays an important role in early embryogenesis. PMID:12679600

Watanabe, Keiko; Toda, Shuji; Yonemitsu, Nobuhisa; Sugihara, Hajime

108

Effect of Amniotic Fluid Stem Cells and Amniotic Fluid Cells on the Wound Healing Process in a White Rat Model  

PubMed Central

Background Amniotic-fluid-derived stem cells and amniocytes have recently been determined to have wound healing effects, but their mechanism is not yet clearly understood. In this study, the effects of amniotic fluid stem cells and amniocytes on wound healing were investigated through animal experiments. Methods On the back of Sprague-Dawley rats, four circular full-thickness skin wounds 2 cm in diameter were created. The wounds were classified into the following four types: a control group using Tegaderm disc wound dressings and experimental groups using collagen discs, amniotic fluid stem cell discs, and amniocyte discs. The wounds were assessed through macroscopic histological examination and immunohistochemistry over a period of time. Results The amniotic fluid stem cell and amniocyte groups showed higher wound healing rates compared with the control group; histologically, the inflammatory cell invasion disappeared more quickly in these groups, and there was more significant angiogenesis. In particular, these groups had significant promotion of epithelial cell reproduction, collagen fiber formation, and angiogenesis during the initial 10 days of the wound healing process. The potency of transforming growth factor-? and fibronectin in the experimental group was much greater than that in the control group in the early stage of the wound healing process. In later stages, however, no significant difference was observed. Conclusions The amniotic fluid stem cells and amniocytes were confirmed to have accelerated the inflammatory stage to contribute to an enhanced cure rate and shortened wound healing period. Therefore, they hold promise as wound treatment agents.

Choi, Dong Sik; Cho, Young Kyoo; Kim, Taek Kyun; Lee, Jeong Woo; Choi, Kang Young; Chung, Ho Yun; Cho, Byung Chae; Byun, Jin Suk

2013-01-01

109

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology.  

PubMed

Stem cells are considered a valuable cellular resource for tissue replacement therapies in most brain disorders. Stem cells have the ability to self-replicate and differentiate into numerous cell types, including neurons, oligodendrocytes and astrocytes. As a result, stem cells have been considered the "holy grail" of modern medical neuroscience. Despite their tremendous therapeutic potential, little is known about the mechanisms that regulate their differentiation. In this review, we analyze stem cells in embryonic and adult brains, and illustrate the differentiation pathways that give origin to most brain cells. We also evaluate the emergent role of the well known anti-oxidant, vitamin C, in stem cell differentiation. We believe that a complete understanding of all molecular players, including vitamin C, in stem cell differentiation will positively impact on the use of stem cell transplantation for neurodegenerative diseases. PMID:23283434

Nualart, Francisco; Salazar, Katterine; Oyarce, Karina; Cisternas, Pedro; Jara, Nery; Silva-Álvarez, Carmen; Pastor, Patricia; Martínez, Fernando; García, Andrea; García-Robles, María de los Ángeles; Tapia, Juan Carlos

2012-01-01

110

Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development  

PubMed Central

Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs.

Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

2012-01-01

111

Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.  

PubMed

Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 ?M of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model. PMID:22843416

Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

2013-10-01

112

Effect of immobilized hyaluronidase on stem and progenitor cells in pulmonary fibrosis.  

PubMed

The effect of immobilized hyaluronidase on stem and progenitor cells of the lungs was studied on the model of partially reversible toxic bleomycin-induced pulmonary fibrosis in C57Bl/6 mice. During the inflammation phase, immobilized hyaluronidase reduced infiltration of alveolar interstitium with hemopoietic stem cells Sca-1(+), c-Kit(+), CD34(-), (CD3, CD45R (B220), Ly6C, Ly6G (Gr1), CD11b (Mac1), TER-119)(-). Improvement of histological parameters of bleomycin lungs during the phase of collagen fiber deposition after the treatment was accompanied by accumulation of mesenchymal multipotent stromal cells (CD31(-), CD34(-), CD45(-), CD44(+), CD73(+), CD90(+), CD106(+)decrease in the population of pan-hemopoietic cells (CD45(+)), accelerated restoration of the content of endothelial cells, and inhibition of clonal activity of fibroblast precursors (CD45(-)). PMID:24771454

Dygai, A M; Skurikhin, E G; Khmelevskaya, E S; Ermakova, N N; Reztsova, A M; Pershina, O V; Krupin, V A; Stepanova, I E; Reztsova, V M; Artamonov, A V; Bekarev, A A; Madonov, P G; Kinsht, D N

2014-02-01

113

Effect of Acanthopanax senticosus stem on mast cell-dependent anaphylaxis.  

PubMed

We studied the effect of Acanthopanax senticosus stem (ACPS) on mast cell-dependent anaphylaxis. ACPS inhibited compound 48/80-induced systemic anaphylaxis at a dose of 1.0 g/kg by 50%. ACPS also inhibited passive cutaneous anaphylaxis reaction and histamine release from mast cells in a dose-dependent manner, respectively. Moreover, ACPS had an inhibitory effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from mast cells. These results indicate that ACPS inhibits mast cell-mediated anaphylaxis in vivo and in vitro murine model. PMID:11849840

Yi, Jin Mu; Hong, Seung Heon; Kim, Jong Ha; Kim, Hyeong Kyun; Song, Ho Joon; Kim, Hyung Min

2002-03-01

114

Intrinsic Ability of Adult Stem Cell in Skeletal Muscle: An Effective and Replenishable Resource to the Establishment of Pluripotent Stem Cells  

PubMed Central

Adult stem cells play an essential role in mammalian organ maintenance and repair throughout adulthood since they ensure that organs retain their ability to regenerate. The choice of cell fate by adult stem cells for cellular proliferation, self-renewal, and differentiation into multiple lineages is critically important for the homeostasis and biological function of individual organs. Responses of stem cells to stress, injury, or environmental change are precisely regulated by intercellular and intracellular signaling networks, and these molecular events cooperatively define the ability of stem cell throughout life. Skeletal muscle tissue represents an abundant, accessible, and replenishable source of adult stem cells. Skeletal muscle contains myogenic satellite cells and muscle-derived stem cells that retain multipotent differentiation abilities. These stem cell populations have the capacity for long-term proliferation and high self-renewal. The molecular mechanisms associated with deficits in skeletal muscle and stem cell function have been extensively studied. Muscle-derived stem cells are an obvious, readily available cell resource that offers promise for cell-based therapy and various applications in the field of tissue engineering. This review describes the strategies commonly used to identify and functionally characterize adult stem cells, focusing especially on satellite cells, and discusses their potential applications.

Fujimaki, Shin; Machida, Masanao; Hidaka, Ryo; Asashima, Makoto; Takemasa, Tohru; Kuwabara, Tomoko

2013-01-01

115

Regulation of reactive oxygen species in stem cells and cancer stem cells.  

PubMed

Stem cells are defined by their ability to self-renew and their multi-potent differentiation capacity. As such, stem cells maintain tissue homeostasis throughout the life of a multicellular organism. Aerobic metabolism, while enabling efficient energy production, also generates reactive oxygen species (ROS), which damage cellular components. Until recently, the focus in stem cell biology has been on the adverse effects of ROS, particularly the damaging effects of ROS accumulation on tissue aging and the development of cancer, and various anti-oxidative and anti-stress mechanisms of stem cells have been characterized. However, it has become increasingly clear that, in some cases, redox status plays an important role in stem cell maintenance, i.e., regulation of the cell cycle. An active area of current research is redox regulation in various cancer stem cells, the malignant counterparts of normal stem cells that are viewed as good targets of cancer therapy. In contrast to cancer cells, in which ROS levels are increased, some cancer stem cells maintain low ROS levels, exhibiting redox patterns that are similar to the corresponding normal stem cell. To fully elucidate the mechanisms involved in stem cell maintenance and to effectively target cancer stem cells, it is essential to understand ROS regulatory mechanisms in these different cell types. Here, the mechanisms of redox regulation in normal stem cells, cancer cells, and cancer stem cells are reviewed. PMID:21448925

Kobayashi, Chiharu I; Suda, Toshio

2012-02-01

116

Stem Cell Treatment of the Heart  

PubMed Central

Stem cells are multipotent, undifferentiated cells capable of multiplication and differentiation. Preliminary experimental evidence suggests that stem cells derived from embryonic or adult tissues (especially bone marrow) may develop into myocardial cells. Some experts believe that this phenomenon occurs naturally in human beings, specifically during recovery from a myocardial infarction. Recently, stem cells have been used with the therapeutic intention of regenerating damaged tissues. Cardiac experiments, mainly with adult homologous stem cells, have proved that this therapy is safe and may improve myocardial vascularization and pump function. We review current fundamental concepts regarding the normal development of embryonic stem cells into myocardial tissue and the heart as a whole. We describe the multiple conditions that naturally enable a stem cell to become a myocardial cell and a group of stem cells to become a heart. We also discuss the challenge of translating basic cellular and molecular mechanisms into effective, clinically relevant treatment options.

Angelini, Paolo; Markwald, Roger R.

2005-01-01

117

Stem cell plasticity  

Microsoft Academic Search

The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack

Uma Lakshmipathy; Catherine Verfaillie

2005-01-01

118

Embryonic stem cells  

Microsoft Academic Search

uman embryonic stem (ES) cells capture the imagination because they are immortal and have an almost unlimited developmental potential (Fig. 1.1: How hESCs are derived). After many months of growth in culture dishes, these remarkable cells maintain the ability to form cells ranging from muscle to nerve to blood — potentially any cell type that makes up the body. The

H. J. Rippon; A. E. Bishop

2004-01-01

119

Laser biomodulation on stem cells  

Microsoft Academic Search

Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in

Timon C. Liu; Rui Duan; Yan Li; Xue-Feng Li; Li-Ling Tan; Songhao Liu

2001-01-01

120

The effect of an external magnetic force on cell adhesion and proliferation of magnetically labeled mesenchymal stem cells  

Microsoft Academic Search

BACKGROUND: As the strategy for tissue regeneration using mesenchymal stem cells (MSCs) for transplantation, it is necessary that MSCs be accumulated and kept in the target area. To accumulate MSCs effectively, we developed a novel technique for a magnetic targeting system with magnetically labeled MSCs and an external magnetic force. In this study, we examined the effect of an external

Toshio Nakamae; Nobuo Adachi; Takaaki Kobayashi; Yoshihiko Nagata; Tomoyuki Nakasa; Nobuhiro Tanaka; Mitsuo Ochi

2010-01-01

121

Effects of Flow-Induced Shear Stress on Limbal Epithelial Stem Cell Growth and Enrichment  

PubMed Central

The roles of limbal epithelial stem cells (LESCs) are widely recognized, but for these cells to be utilized in basic research and potential clinical applications, researchers must be able to efficiently isolate them and subsequently maintain their stemness in vitro. We aimed to develop a biomimetic environment for LESCs involving cells from their in vivo niche and the principle of flow-induced shear stress, and to subsequently demonstrate the potential of this novel paradigm. LESCs, together with neighboring cells, were isolated from the minced limbal tissues of rabbits. At days 8 and 9 of culture, the cells were exposed to a steady flow or intermittent flow for 2 h per day in a custom-designed bioreactor. The responses of LESCs and epithelial cells were assessed at days 12 and 14. LESCs and epithelial cells responded to both types of flow. Proliferation of LESCs, as assessed using a BrdU assay, was increased to a greater extent under steady flow conditions. Holoclones were found under intermittent flow, indicating that differentiation into transient amplifying cells had occurred. Immunofluorescent staining of Bmi-1 suggested that steady flow has a positive effect on the maintenance of stemness. This finding was confirmed by real-time PCR. Notch-1 and p63 were more sensitive to intermittent flow, but this effect was transient. K3 and K12 expression, indicative of differentiation of LESCs into epithelial cells, was induced by flow and lasted longer under intermittent flow conditions. In summary, culture of LESCs in a bioreactor under a steady flow paradigm, rather than one of intermittent flow, is beneficial for both increasing proliferation and maintaining stemness. Conversely, intermittent flow appears to induce differentiation of LESCs. This novel experimental method introduces micro-mechanical stimuli to traditional culture techniques, and has potential for regulating the proliferation and differentiation of LESCs in vitro, thereby facilitating research in this field.

Kang, Yun Gyeong; Shin, Ji Won; Park, So Hee; Oh, Min-Jae; Park, Hyo Soon; Shin, Jung-Woog; Kim, Su-Hyang

2014-01-01

122

Stem Cell Transplantation Methods  

Microsoft Academic Search

\\u000a \\u000a Just a few short years ago, we still used to think that we were born with a finite number of irreplaceable neurons. However,\\u000a in recent years, there has been increasingly persuasive evidence that suggests that neural stem cell (NSC) maintenance and\\u000a differentiation continue to take place throughout the mammal’s lifetime. Studies suggest that neural stem cells not only persist\\u000a to

Kimberly D. Tran; Allen Ho; Rahul Jandial

123

Effect of transplantation of human embryonic stem cell-derived neural progenitor cells on adult neurogenesis in aged hippocampus  

PubMed Central

Adult neurogenesis occurs within the special microenvironment in the subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle of the mammalian brain. The special microenvironment is known as neurogenic niches. Multiple cell types, including endothelial cells, astroglia, ependymal cells, immature progeny of neural stem cells, and mature neurons, comprise the neurogenic niche. Differentiation of embryonic stem cells towards the neural lineage results in the generation of different neuronal subtypes and non-neuronal cells (mainly astrocytes). Therefore, it is reasonable to hypothesize that transplantation of human embryonic stem cell-derived neural progenitor cells can be used to modify neurogenic niches for facilitating adult neurogenesis. Furthermore, if generated new neurons are functionally integrated into the existing circuits of the aged hippocampus, synaptic plasticity in the hippocampus and learning/memory functions in aged mice should be enhanced. In this article, we provide a comprehensive review of the concepts in the regulation of adult neurogenesis by neurogenic niches and discuss the molecular mechanisms underlying the effect of stem cell transplantation on adult neurogenesis in aged hippocampus

Liu, Sufang; Li, Changsheng; Xing, Ying; Tao, Feng

2014-01-01

124

Limbal Stem Cells in Review  

PubMed Central

The ocular surface consists of two distinct types of epithelial cells; conjunctival and corneal. Although anatomically continuous, these epithelia comprise two distinct cell populations. Corneal stem cells are located at the limbus. The microenvironment of the limbus is important in maintaining “stemness” of the stem cells and also acts as a barrier to conjunctival epithelial cells preventing them from migration onto the corneal surface.Damage to the limbus results in varying degrees of limbal stem cell deficiency with characteristic clinical features including conjunctivalization of the cornea. Regenerative management of corneal conjunctivalization utilizing stem cells comprises of two approaches; limbal auto- or allografts by using existing stem cells and induction and regeneration of ocular tissues from embryonic stem cells. Herein, we review stem cells and limbal stem cells in particular, types of epithelial cells in the cornea, markers of corneal epithelial cells in different stages, as well as the current approach to corneal epithelial regeneration.

Ebrahimi, Marzieh; Taghi-Abadi, Ehsan; Baharvand, Hossein

2009-01-01

125

Glioblastoma stem cells.  

PubMed

Glioblastomas are highly malignant primary brain tumors with one of the worst survival rates among all human cancers. With a more profound understanding of the cellular and molecular mechanisms of tumor initiation and acquired resistance to conventional radio- and chemotherapy, novel therapeutic targets might be discovered to optimize therapeutic approaches. In this regard, the identification of a small cellular subpopulation, called glioblastoma stem cell or stem-like cells or glioma-initiating cells or brain tumor propagating cells, has gained attention. In this article, we briefly summarize the current state of knowledge about this tumor cell population and discuss future directions for basic and clinical research. PMID:21253762

Tabatabai, Ghazaleh; Weller, Michael

2011-03-01

126

Prostaglandin E2 (PGE2) exerts biphasic effects on human tendon stem cells.  

PubMed

Prostaglandin E2 (PGE2) has been reported to exert different effects on tissues at low and high levels. In the present study, cell culture experiments were performed to determine the potential biphasic effects of PGE2 on human tendon stem/progenitor cells (hTSCs). After treatment with PGE2, hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE2 (>1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (<1 ng/ml), PGE2 markedly enhanced hTSC proliferation. The expression levels of stem cell marker genes, specifically SSEA-4 and Stro-1, were more extensive in hTSCs treated with low concentrations of PGE2 than in cells treated with high levels of PGE2. Moreover, high levels of PGE2 induced hTSCs to differentiate aberrantly into non-tenocytes, which was evident by the high levels of PPAR?, collagen type II, and osteocalcin expression in hTSCs treated with PGE2 at concentrations >1 ng/ml. The findings of this study reveal that PGE2 can exhibit biphasic effects on hTSCs, indicating that while high PGE2 concentrations may be detrimental to tendons, low levels of PGE2 may play a vital role in the maintenance of tendon homeostasis in vivo. PMID:24504456

Zhang, Jianying; Wang, James H-C

2014-01-01

127

Prostaglandin E2 (PGE2) Exerts Biphasic Effects on Human Tendon Stem Cells  

PubMed Central

Prostaglandin E2 (PGE2) has been reported to exert different effects on tissues at low and high levels. In the present study, cell culture experiments were performed to determine the potential biphasic effects of PGE2 on human tendon stem/progenitor cells (hTSCs). After treatment with PGE2, hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE2 (>1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (<1 ng/ml), PGE2 markedly enhanced hTSC proliferation. The expression levels of stem cell marker genes, specifically SSEA-4 and Stro-1, were more extensive in hTSCs treated with low concentrations of PGE2 than in cells treated with high levels of PGE2. Moreover, high levels of PGE2 induced hTSCs to differentiate aberrantly into non-tenocytes, which was evident by the high levels of PPAR?, collagen type II, and osteocalcin expression in hTSCs treated with PGE2 at concentrations >1 ng/ml. The findings of this study reveal that PGE2 can exhibit biphasic effects on hTSCs, indicating that while high PGE2 concentrations may be detrimental to tendons, low levels of PGE2 may play a vital role in the maintenance of tendon homeostasis in vivo.

Zhang, Jianying; Wang, James H-C.

2014-01-01

128

Effects of medium supplements on proliferation, differentiation potential, and in vitro expansion of mesenchymal stem cells.  

PubMed

Mesenchymal stem cells (MSCs) possess great potential for use in regenerative medicine. However, their clinical application may be limited by the ability to expand their cell numbers in vitro while maintaining their differential potentials and stem cell properties. Thus the aim of this study was to test the effect of a range of medium supplements on MSC self-renewal and differentiation potential. Cells were cultured until confluent and subcultured continuously until reaching senescence. Medium supplementation with fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-BB, ascorbic acid (AA), and epidermal growth factor (EGF) both increased proliferation rate and markedly increased number of cell doublings before reaching senescence, with a greater than 1,000-fold increase in total cell numbers for AA, FGF-2, and PDGF-BB compared with control cultures. Long-term culture was associated with loss of osteogenic/adipocytic differentiation potential, particularly with FGF-2 supplementation but also with AA, EGF, and PDGF-BB. In addition FGF-2 resulted in reduction in expression of CD146 and alkaline phosphatase, but this was partially reversible on removal of the supplement. Cells expressed surface markers including CD146, CD105, CD44, CD90, and CD71 by flow cytometry throughout, and expression of these putative stem cell markers persisted even after loss of differentiation potentials. Overall, medium supplementation with FGF-2, AA, EGF, and PDGF-BB greatly enhanced the total in vitro expansion capacity of MSC cultures, although differentiation potentials were lost prior to reaching senescence. Loss of differentiation potential was not reflected by changes in stem cell surface marker expression. PMID:23197689

Gharibi, Borzo; Hughes, Francis J

2012-11-01

129

Germline Stem Cells  

PubMed Central

Sperm and egg production requires a robust stem cell system that balances self-renewal with differentiation. Self-renewal at the expense of differentiation can cause tumorigenesis, whereas differentiation at the expense of self-renewal can cause germ cell depletion and infertility. In most organisms, and sometimes in both sexes, germline stem cells (GSCs) often reside in a defined anatomical niche. Factors within the niche regulate a balance between GSC self-renewal and differentiation. Asymmetric division of the germline stem cell to form daughter cells with alternative fates is common. The exception to both these tendencies is the mammalian testis where there does not appear to be an obvious anatomical niche and where GSC homeostasis is likely accomplished by a stochastic balance of self-renewal and differentiation and not by regulated asymmetric cell division. Despite these apparent differences, GSCs in all organisms share many common mechanisms, although not necessarily molecules, to guarantee survival of the germline.

Spradling, Allan; Fuller, Margaret T.; Braun, Robert E.; Yoshida, Shosei

2011-01-01

130

Inhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation  

PubMed Central

Background IL-17, a Th17 cell-derived proinflammatory molecule, has been found to play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). While IL-17 receptor (IL-17R) is expressed in many immune-related cells, microglia, and astrocytes, it is not known whether IL-17 exerts a direct effect on neural stem cells (NSCs) and oligodendrocytes, thus inducing inflammatory demyelination in the central nervous system. Methods We first detected IL-17 receptor expression in NSCs with immunostaining and real time PCR. We then cultured NSCs with IL-17 and determined NSC proliferation by neurosphere formation capability and cell number count, differentiation by immunostaining neural specific markers, and apoptosis of NSCs by flow cytometry. Results NSCs constitutively express IL-17R, and when the IL-17R signal pathway was activated by adding IL-17 to NSC culture medium, the number of NSCs was significantly reduced and their ability to form neurospheres was greatly diminished. IL-17 inhibited NSC proliferation, but did not induce cytotoxicity or apoptosis. IL-17 hampered the differentiation of NSCs into astrocytes and oligodendrocyte precursor cells (OPCs). The effects of IL-17 on NSCs can be partially blocked by p38 MAPK inhibitor. Conclusions IL-17 blocks proliferation of NSCs, resulting in significantly reduced numbers of astrocytes and OPCs. Thus, in addition to its proinflammatory role in the immune system, IL-17 may also play a direct role in blocking remyelination and neural repair in the CNS.

2013-01-01

131

Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation  

Microsoft Academic Search

Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically

B. R. Leigh; W. Khan; S. L. Hancock

1995-01-01

132

Brain tumour stem cells  

Microsoft Academic Search

The dogma that the genesis of new cells is a negligible event in the adult mammalian brain has long influenced our perception and understanding of the origin and development of CNS tumours. The discovery that new neurons and glia are produced throughout life from neural stem cells provides new possibilities for the candidate cells of origin of CNS neoplasias. The

Rossella Galli; Brent A. Reynolds; Angelo L. Vescovi

2006-01-01

133

Encapsulated stem cells for cancer therapy  

PubMed Central

Stem cells have inherent tumor?trophic migratory properties and can serve as vehicles for delivering effective, targeted therapy to isolated tumors and metastatic disease, making them promising anti?cancer agents. Encapsulation of therapeutically engineered stem cells in hydrogels has been utilized to provide a physical barrier to protect the cells from hostile extrinsic factors and significantly improve the therapeutic efficacy of transplanted stem cells in different models of cancer. This review aims to discuss the potential of different stem cell types for cancer therapy, various engineered stem cell based therapies for cancer, stem cell encapsulation process and provide an in depth overview of current applications of therapeutic stem cell encapsulation in the highly malignant brain tumor, glioblastoma multiforme (GBM), as well as the prospects for their clinical translation.

2013-01-01

134

Cell-Replacement Therapy with Stem Cells in Neurodegenerative Diseases  

Microsoft Academic Search

In the past few years, research on stem cells has expanded greatly as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several mechanisms such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation may explain positive

Vincenzo Silani; Massimo Corbo

2004-01-01

135

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect  

Microsoft Academic Search

Natural killer (NK) cell alloreactivity is reported to mediate strong GvL (graft versus leukemia) effect in patients after haploidentical stem-cell transplantation (SCT) for acute myeloid leukemia (AML). Because subsequent immune reconstitu- tion remains a major concern, we studied NK-cell recovery in 10 patients with AML who received haplomismatched SC trans- plants, among whom no GvL effect was observed, despite the

Stephanie Nguyen; Nathalie Dhedin; Jean-Paul Vernant; Mathieu Kuentz; Ahmad Al Jijakli; Nathalie Rouas-Freiss; Edgardo D. Carosella; Ali Boudifa; Patrice Debre; Vincent Vieillard; Clinique Hôpital; Henri Mondor

2005-01-01

136

Lgr5(+) gastric stem cells divide symmetrically to effect epithelial homeostasis in the pylorus.  

PubMed

The pyloric epithelium continuously self-renews throughout life, driven by limited reservoirs of resident Lgr5+ adult stem cells. Here, we characterize the population dynamics of these stem cells during epithelial homeostasis. Using a clonal fate-mapping strategy, we demonstrate that multiple Lgr5+ cells routinely contribute to epithelial renewal in the pyloric gland and, similar to what was previously observed in the intestine, a balanced homeostasis of the glandular epithelium and stem cell pools is predominantly achieved via neutral competition between symmetrically dividing Lgr5+ stem cells. Additionally, we document a lateral expansion of stem cell clones via gland fission under nondamage conditions. These findings represent a major advance in our basic understanding of tissue homeostasis in the stomach and form the foundation for identifying altered stem cell behavior during gastric disease. PMID:24209744

Leushacke, Marc; Ng, Annie; Galle, Joerg; Loeffler, Markus; Barker, Nick

2013-10-31

137

The effects of microenvironment on wound healing by keratinocytes derived from mesenchymal stem cells.  

PubMed

Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into various cell types, including keratinocyte-like cells, within suitable microniches. In this study, we aimed to investigate the effects of culture media, cell coculture, and a tissue-engineering biocomposite on the differentiation of mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were transfected using pCX-EGFP expressing green fluorescence, were used to track MESC-derived keratinocytes. Weak expression of the keratinocyte early marker Cytokeratin 14 (CK-14) was observed up to 12 days when MESCs were cultured in a keratinocyte culture medium on tissue culture plastic and on a gelatin/collagen/polycaprolactone (GCP) biocomposite. MESCs cocultured with human keratinocyte cells (HKCs) also expressed CK-14, but did not express CK-14 when cocultured with human fibroblast cells (HFCs). Furthermore, CK-14 expression was observed when MESCs were cocultured by seeding HKCs or HFCs on the same or opposite side of the GCP biocomposite. The highest CK-14 expression was observed by seeding MESCs and HKCs on the same side of the GCP composite and with HFCs on the opposite side. To verify the effectiveness of wound healing in vivo, adipose-derived stem cells were applied to treat surgical wounds in nude mice. An obvious epidermis multilayer and better collagen deposition during wound healing were observed, as assessed by Masson staining. This study demonstrated the potential of keratinocyte-like differentiation from mesenchymal stem cells for use in promoting wound closure and skin regeneration. PMID:24284744

Lin, Yi-Han; Fu, Keng-Yen; Hong, Po-Da; Ma, Hsu; Liou, Nien-Hsien; Ma, Kuo-Hsing; Liu, Jiang-Chuan; Huang, Kun-Lun; Dai, Lien-Guo; Chang, Shun-Cheng; Yi-Hsin Chan, James; Chen, Shyi-Gen; Chen, Tim-Mo; Dai, Niann-Tzyy

2013-12-01

138

Cytotoxic and Genotoxic effects of Arsenic and Lead on Human Adipose Derived Mesenchymal Stem Cells (AMSCs).  

PubMed

Arsenic and lead, known to have genotoxic and mutagenic effects, are ubiquitously distributed in the environment. The presence of arsenic in drinking water has been a serious health problem in many countries. Human exposure to these metals has also increased due to rapid industrialization and their use in formulation of many products. Liposuction material is a rich source of stem cells. In the present study cytotoxic and genotoxic effects of these metals were tested on adipose derived mesenchymal stem cells (AMSCs). Cells were exposed to 1-10 ?g/ml and 10-100 ?g/ml concentration of arsenic and lead, respectively, for 6, 12, 24 and 48 h. The cytotoxic effects were measured by neutral red uptake assay, while the genotoxic effects were tested by comet assay. The growth of cells decreased with increasing concentration and the duration of exposure to arsenic. Even the morphology of cells was changed; they became round at 10 ?g /ml of arsenic. The cell growth was also decreased after exposure to lead, though it proved to be less toxic when cells were exposed for longer duration. The cell morphology remained unchanged. DNA damage was observed in the metal treated cells. Different parameters of comet assay were investigated for control and treated cells which indicated more DNA damage in arsenic treated cells compared to that of lead. Intact nuclei were observed in control cells. Present study clearly demonstrates that both arsenic and lead have cytotoxic and genotoxic effects on AMSCs, though arsenic compared to lead has more deleterious effects on AMSCs. PMID:24693207

Ar, Shakoori; A, Ahmad

2013-01-01

139

Scientific institutions and effective governance: a case study of Chinese stem cell research  

PubMed Central

In terms of stem cell research, China appears both as a “powerhouse” armed with state-of-the-art facilities, internationally trained personnel and permissive regulation and as a “bit player,” with its capability for conducting high quality research still in question. The gap between China’s assiduous endeavors and the observed outcome is due to a number of factors. Based on interviews with 48 key stakeholders active in Chinese stem cell research, this article examines how the structure of scientific institutions has affected effective governance in China. It is demonstrated that despite China’s recent efforts to attract highly competent researchers and to launch new regulatory initiatives, the effects of these attempts have been diminished by an absence of middle-layer positions within research teams and by the uncoordinated administrative structures among regulatory bodies.

Zhang, Joy Yueyue

2013-01-01

140

Effects of Growth Factors on Dental Stem/ProgenitorCells  

PubMed Central

Synopsis The primary goal of regenerative endodontics is to restore the vitality and functions of the dentin-pulp complex, as opposed to filing of the root canal with bioinert materials. Structural restoration is also important but is likely secondary to vitality and functions. Myriads growth factors regulate multiple cellular functions including migration, proliferation, differentiation and apoptosis of several cell types that are intimately involved in dentin-pulp regeneration: odontoblasts, interstitial fibroblasts, vascular-endothelial cells and sprouting nerve fibers. Recent work showing that growth factor delivery, without cell transplantation, can yield pulp-dentin like tissues in vivo provides one of the tangible pathways for regenerative endodontics. This review synthesizes our knowledge on a multitude of growth factors that are known or anticipated to be efficacious in dental pulp-dentin regeneration.

Kim, Sahng G.; Solomon, Charles; Zheng, Ying; Suzuki, Takahiro; Mo, Chen; Song, Songhee; Jiang, Nan; Cho, Shoko; Zhou, Jian; Mao, Jeremy J.

2014-01-01

141

Challenges for heart disease stem cell therapy  

PubMed Central

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.

Hoover-Plow, Jane; Gong, Yanqing

2012-01-01

142

Cell-free derivatives from mesenchymal stem cells are effective in wound therapy  

PubMed Central

AIM: To compare the efficacy of cell-free derivatives from Bone marrow derived human mesenchymal stem cells (hMSCs) in wound therapy. METHODS: hMSCs have been shown to play an important role in wound therapy. The present study sought to compare efficacy of hMSCs and cell-free derivatives of hMSCs, which may be clinically more relevant as they are easier to prepare, formulate and transport. hMSCs were isolated from human bone marrow and cultured. Multi lineage differentiation of hMSCs was performed to confirm their identity. The ability of hMSCs to migrate was evaluated using in vitro and in vivo migration assays. Cell lysates and conditioned medium concentrate was prepared from hMSCs (see Methods for details). Wounds were induced in mice and wound areas were measure before and after cell and cell-free derivative treatment. RNA and proteins were extracted from the skin and cytokine levels were measured. RESULTS: Co-culture of hMSCs with keratinocytes resulted in increased expression of CXCL-12 (SDF1) and ENA78 (CXCL-5) in the conditioned media indicating that the hMSCs can respond to signals from keratinocytes. Accelerated wound closure was observed when hMSCs were injected near the site of excisional wounds in athymic as well as NOD/SCID mice. Interestingly, cell-free lysates prepared from hMSCs were also effective in inducing accelerated wound closure and increased expression of SDF1 and CXCL-5 at the wound bed. Additionally, concentrated media from hMSCs as well as an emulsion containing lysates prepared from hMSCs was also found to be more effective in rapid re-epithelialization than fibroblasts or vehicle-alone control. Use of cell-free derivatives may help replace expensive wound care approaches including use of growth factors, epidermal/dermal substitutes, synthetic membranes, cytokines, and matrix components, and most importantly avoid transmission of pathogens from human and animal products. CONCLUSION: These results encourage development of derivatives of hMSCs for wound care and re-epithelialization applications.

Mishra, Pravin J; Mishra, Prasun J; Banerjee, Debabrata

2012-01-01

143

Graft-versus-host effect after allogeneic hematopoietic stem cell transplantation: GVHD and GVL  

Microsoft Academic Search

The development of a graft-versus-host reaction after allogeneic hematopoietic stem cell transplantation is an important determinant of the transplant outcome. A better understanding and improved management of the graft-versus-host reaction should allow improved prevention and treatment of graft-versus-host disease and the development of new strategies to enhance a graft-versus-leukemia effect and to decrease the incidence of leukemic relapse after transplantation.

Richard A Nash; Rainer Storb

1996-01-01

144

The behavioral effect of human mesenchymal stem cell transplantation in cold brain injured rats  

Microsoft Academic Search

We investigated the effect of stereotaxically transplanted human mesenchymal stem cells (hMSCs) on behavioral change after\\u000a traumatic cold brain injury in adult rats. Cortical lesions (n = 20) were induced by touching a metal stamp, cooled with liquid nitrogen, to the dura over the forelimb motor cortex of\\u000a adult rats. The procedure produced a localized lesion, and the animals showed

Y. H. Cho; H. S. Kim; K. H. Lee; Y. E. Lee; J. W. Chang

145

Stem cells in microfluidics  

PubMed Central

Microfluidic techniques have been recently developed for cell-based assays. In microfluidic systems, the objective is for these microenvironments to mimic in vivo surroundings. With advantageous characteristics such as optical transparency and the capability for automating protocols, different types of cells can be cultured, screened, and monitored in real time to systematically investigate their morphology and functions under well-controlled microenvironments in response to various stimuli. Recently, the study of stem cells using microfluidic platforms has attracted considerable interest. Even though stem cells have been studied extensively using bench-top systems, an understanding of their behavior in in vivo-like microenvironments which stimulate cell proliferation and differentiation is still lacking. In this paper, recent cell studies using microfluidic systems are first introduced. The various miniature systems for cell culture, sorting and isolation, and stimulation are then systematically reviewed. The main focus of this review is on papers published in recent years studying stem cells by using microfluidic technology. This review aims to provide experts in microfluidics an overview of various microfluidic systems for stem cell research.

Wu, Huei-Wen; Lin, Chun-Che; Lee, Gwo-Bin

2011-01-01

146

Effects of tilorone on hemopoietic stem cells and on the development of Friend leukemia.  

PubMed

Hematological effects of tilorone, an interferon inducer, on the hematopoietic cell system of normal CBA/Ca mice and on the development of Friend virus (FV-P)-induced polycythemia in DBA/2 mice were studied. In normal mice 80 mg/kg IP had a marked depressive effect on pluripotent (CFU-s), granuloid committed (CFU-C), and erythroid committed (CFU-E) stem cells with regeneration between days 5 and 12. In bone marrow smears only lymphopenia was detected. Treatment of mice before FV-P infection caused a slight retardation in the development of the splenomegaly and the transformation of bone marrow cells to Ep independence. Repeated treatment after FV-P infection also reduced the increase in spleen weight and the development of reticulocytosis, but the Ep independence of bone marrow and spleen cells was not influenced. In vitro exposure of normal cells and cells from FV-P-infected animals to the drug showed the same sensitivity of colony growth in normal as well as in Ep-independent CFU-E. The action of the drug on Friend leukemia is at least in part considered a toxic effect on the hematopoietic stem cell system. PMID:7460194

Seidel, H J; Opitz, U; Kreja, L

1980-01-01

147

[Leukemia stem cell].  

PubMed

Cancer is the main cause of death in advanced countries. It has become progressively clear that cancer cells are distributed in a developmental hierarchy, in which whole cancer tissues originate from cancer stem cells(CSCs). CSCs were first discovered in a case of acute myeloid leukemia. Leukemia stem cells(LSCs)are resistant to conventional chemotherapies because of their dormancy and are therefore the cause of minimal residual disease and relapse. Many investigators are working to develop novel therapeutic strategies for eliminating LSCs. LSC biology is discussed in the first part of this review, and the therapeutic approach to LSC targeting is described in the latter part. PMID:24743272

Iwasaki, Hiromi

2014-03-01

148

Effects of inflorescence stem structure and cell wall components on the mechanical strength of inflorescence stem in herbaceous peony.  

PubMed

Herbaceous peony (Paeonia lactiflora Pall.) is a traditional famous flower, but its poor inflorescence stem quality seriously constrains the development of the cut flower. Mechanical strength is an important characteristic of stems, which not only affects plant lodging, but also plays an important role in stem bend or break. In this paper, the mechanical strength, morphological indices and microstructure of P. lactiflora development inflorescence stems were measured and observed. The results showed that the mechanical strength of inflorescence stems gradually increased, and that the diameter of inflorescence stem was a direct indicator in estimating mechanical strength. Simultaneously, with the development of inflorescence stem, the number of vascular bundles increased, the vascular bundle was arranged more densely, the sclerenchyma cell wall thickened, and the proportion of vascular bundle and pith also increased. On this basis, cellulose and lignin contents were determined, PlCesA3, PlCesA6 and PlCCoAOMT were isolated and their expression patterns were examined including PlPAL. The results showed that cellulose was not strictly correlated with the mechanical strength of inflorescence stem, and lignin had a significant impact on it. In addition, PlCesA3 and PlCesA6 were not key members in cellulose synthesis of P. lactiflora and their functions were also different, but PlPAL and PlCCoAOMT regulated the lignin synthesis of P. lactiflora. These data indicated that PlPAL and PlCCoAOMT could be applied to improve the mechanical strength of P. lactiflora inflorescence stem in genetic engineering. PMID:22606025

Zhao, Daqiu; Han, Chenxia; Tao, Jun; Wang, Jing; Hao, Zhaojun; Geng, Qingping; Du, Bei

2012-01-01

149

Short-term effects of 7-ketocholesterol on human adipose tissue mesenchymal stem cells in vitro.  

PubMed

Oxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and non-enzymatic oxidation. Among them, 7-ketocholesterol (7-KC) is one of the most important. It has potent effects in cell death processes, including cytoxicity and apoptosis induction. Mesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Very little is known about the effects of oxysterols in MSCs. Here, we describe the short-term cytotoxic effect of 7-ketocholesterol on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from two young, healthy women. After 24h incubation with 7-KC, mitochondrial hyperpolarization was observed, followed by a slight increase in the level of apoptosis and changes in actin organization. Finally, the IC50 of 7-KC was higher in these cells than has been observed or described in other normal or cancer cell lines. PMID:24491549

Levy, Débora; Ruiz, Jorge Luis Maria; Celestino, Andrea Turbuck; Silva, Suelen Feitoza; Ferreira, Adilson Kleber; Isaac, Cesar; Bydlowski, Sérgio Paulo

2014-04-11

150

Stem Cell Research  

SciTech Connect

We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

Catherine Verfaillie

2009-01-23

151

Stem cells and cancer  

Microsoft Academic Search

The cell of origin of cancer has been a strongly debated topic through out the history of cancer research. This review provides a historic framework and a synopsis of how the theories of cancer initiation and progression evolved from early times to the present day. We present the concept of a cancer stem cell, and review for you the literature

JeanMarie Houghton; Alexei Morozov; Iva Smirnova; Timothy C. Wang

2007-01-01

152

Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells  

PubMed Central

Background: Glioblastoma multiforme (GBM) cells are resistant to anticancer drugs. Cancer stem cells (CSCs) are a key mediator of chemoresistance. We have reported that disulfiram (DS), an aldehyde dehydrogenase (ALDH) inhibitor, targets breast CSC-like cells. In this study, the effect of DS and combination of DS and gemcitabine (dFdC) on GBM cells and GBM stem-like cells was investigated. Methods: 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI)-isobologram, western blot, luciferase reporter gene assay, electrophoretic mobility-shift assay and ALDH analysis were used in this study. Results: Disulfiram is cytotoxic in GBM cell lines in a copper (Cu)-dependent manner. Disulfiram/copper enhances the cytotoxicity of dFdC. Combination index-isobologram analysis indicates a synergistic effect between DS/Cu and dFdC. Disulfiram/copper induces reactive oxygen species (ROS), activates JNK and p38 pathways and inhibits nuclear factor-kappa B activity in GBM cell lines. Disulfiram/copper may trigger intrinsic apoptotic pathway via modulation of the Bcl2 family. Disulfiram/copper abolishes stem-like cell population in GBM cell lines. Conclusion: Our findings indicate that the cytotoxicity of DS/Cu and the enhancing effect of DS/Cu on the cytotoxicity of dFdC in GBM stem-like cells may be caused by induction of ROS and inhibition of both ALDH and the NFkB pathway. Both DS and dFdC can traverse the blood–brain barrier. Further study may lead them into GBM chemotherapy.

Liu, P; Brown, S; Goktug, T; Channathodiyil, P; Kannappan, V; Hugnot, J-P; Guichet, P-O; Bian, X; Armesilla, A L; Darling, J L; Wang, W

2012-01-01

153

Endothelial differentiation of adipose-derived stem cells: Effects of endothelial cell growth supplement and shear force  

PubMed Central

Background Adipose tissue is a readily available source of multipotent adult stem cells for use in tissue engineering/regenerative medicine. Various growth factors have been used to stimulate acquisition of endothelial characteristics by adipose-derived stem cells (ASC). Herein we study the effects of endothelial cell growth supplement (ECGS) and physiologic shear force on the differentiation of ASC into endothelial cells. Methods Human ASC (CD13+29+90+31?45?) were isolated from peri-umbilical fat, cultured in ECGS media (for up to three weeks) and exposed to physiological shear force (12 dynes for up to eight days) in vitro. Endothelial phenotype was defined by cord formation on Matrigel, acetylated-LDL (acLDL) uptake, and expression of nitric oxide synthase (eNOS), von Willebrand factor (vWF), and CD31 (PECAM). Additionally, cell thrombogenicity was evaluated by seeding canine autologous ASC onto vascular grafts implanted within the canine arterial circulation for two weeks. Results We found that undifferentiated ASC did not display any of the noted endothelial characteristics. After culture in ECGS, ASC formed cords in Matrigel, but failed to take up acLDL or express the molecular markers. Subsequent exposure to shear resulted in stem cell realignment, acLDL uptake and expression of CD31; eNOS and vWF expression was still not observed. Grafts seeded with cells grown in ECGS (±shear) remained patent (six of seven) at two weeks but had a thin coat of fibrin along the luminal surfaces. Conclusions This study suggests that: 1) ECGS and shear promote the expression of several endothelial characteristics in human adipose-derived stem cells, but not eNOS or vWF, 2) their combined effects appear synergistic, and 3) stem cells differentiated in ECGS appear mildly thrombogenic in vivo, possibly related, in part, to insufficient eNOS expression. Thus, while the acquisition of several endothelial characteristics by adult stem cells derived from adipose tissue suggests these cells are a viable source of autologous cells for cardiovascular regeneration, further stimulation/modifications are necessary prior to using them as a true endothelial cell replacement.

Fischer, Lauren J.; McIlhenny, Stephen; Tulenko, Thomas; Golesorkhi, Negar; Zhang, Ping; Larson, Robert; Lombardi, Joseph; Shapiro, Irving; DiMuzio, Paul J.

2009-01-01

154

Effects of heat shock on survival, proliferation and differentiation of mouse neural stem cells.  

PubMed

Hyperthermia during pregnancy is a significant cause of reproductive problems ranging from abortion to congenital defects of the central nervous system (CNS), including neural tube defects and microcephaly. Neural stem cells (NSCs) can proliferate and differentiate into neurons and glia, playing a key role in the formation of the CNS. Here, we examined the effects of heat shock on homogeneous proliferating NSCs derived from mouse embryonic stem cells. After heat shock at 42 °C for 20 min, the proliferating NSCs continued to proliferate, although subtle changes were observed in gene expression and cell survival and proliferation. In contrast, heat shock at 43 °C caused a variety of responses: the up-regulation of genes encoding heat shock proteins (HSP), induction of apoptosis, temporal inhibition of cell proliferation and retardation of differentiation. Finally, effects of heat shock at 44 °C were severe, with almost all cells disappearing and the remaining cells losing the capacity to proliferate and differentiate. These temperature-dependent effects of heat shock on NSCs may be valuable in elucidating the mechanisms by which hyperthermia during pregnancy causes various reproductive problems. PMID:24316183

Omori, Hiroyuki; Otsu, Masahiro; Suzuki, Asami; Nakayama, Takashi; Akama, Kuniko; Watanabe, Masaru; Inoue, Nobuo

2014-02-01

155

Stem cells and the Planarian Schmidtea mediterranea  

Microsoft Academic Search

In recent years, stem cells have been heralded as potential therapeutic agents to address a large number of degenerative diseases. Yet, in order to rationally utilize these cells as effective therapeutic agents, and\\/or improve treatment of stem-cell-associated malignancies such as leukemias and carcinomas, a better understanding of the basic biological properties of stem cells needs to be acquired. A major

Alejandro Sánchez Alvarado

2007-01-01

156

Blood and Marrow Stem Cell Transplant  

MedlinePLUS

... Twitter. What Is a Blood and Marrow Stem Cell Transplant? A blood and marrow stem cell transplant ... the missing white blood cells. Types of Stem Cell Transplants The two main types of stem cell ...

157

Xenobiotic effects on intestinal stem cell proliferation in adult honey bee (Apis mellifera L) workers.  

PubMed

The causes of the current global decline in honey bee health are unknown. One major group of hypotheses invokes the pesticides and other xenobiotics to which this important pollinator species is often exposed. Most studies have focused on mortality or behavioral deficiencies in exposed honey bees while neglecting other biological functions and target organs. The midgut epithelium of honey bees presents an important interface between the insect and its environment. It is maintained by proliferation of intestinal stem cells throughout the adult life of honey bees. We used caged honey bees to test multiple xenobiotics for effects on the replicative activity of the intestinal stem cells under laboratory conditions. Most of the tested compounds did not alter the replicative activity of intestinal stem cells. However, colchicine, methoxyfenozide, tetracycline, and a combination of coumaphos and tau-fluvalinate significantly affected proliferation rate. All substances except methoxyfenozide decreased proliferation rate. Thus, the results indicate that some xenobiotics frequently used in apiculture and known to accumulate in honey bee hives may have hitherto unknown physiological effects. The nutritional status and the susceptibility to pathogens of honey bees could be compromised by the impacts of xenobiotics on the maintenance of the midgut epithelium. This study contributes to a growing body of evidence that more comprehensive testing of xenobiotics may be required before novel or existing compounds can be considered safe for honey bees and other non-target species. PMID:24608542

Forkpah, Cordelia; Dixon, Luke R; Fahrbach, Susan E; Rueppell, Olav

2014-01-01

158

Advancing Stem Cell Biology toward Stem Cell Therapeutics  

PubMed Central

Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of articles outlining the current status, opportunities, and challenges surrounding the clinical translation of stem cell therapeutics for specific medical conditions.

Scadden, David; Srivastava, Alok

2014-01-01

159

Stem Cell Transplantation Increases Antioxidant Effects in Diabetic Mice  

PubMed Central

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, blood glucose levels and insulin, and increased plasma adiponectin levels. The upregulation of HO-1 was associated with significantly (p<0.05) increased levels of peNOS and pAKT, but decreased levels of iNOS in the kidneys of db/db mice. Plasma creatinine levels also decreased (p<0.05), and the expression of type IV collagen was improved. Thus IBM-BMT+TT unregulated the expression of HO-1, peNOS and pAKT, while decreasing iNOS levels in the kidney of db/db mice. This was associated with an improvement in renal function.

Li, Ming; Vanella, Luca; Zhang, Yuming; Shi, Ming; Takaki, Takashi; Shapiro, Joseph I; Ikehara, Susumu

2012-01-01

160

Retention of stem cell plasticity in avian primitive streak cells and the effects of local microenvironment.  

PubMed

Primitive streak (PS) is the first structure occurring in embryonic gastrulation, in which the epiblast cells undergo the epithelial-mesenchymal transition to become the loose mesoderm cells subsequently. Because the mesoderm cells departing from different portions of PS are blessed with disparate migration trajectory and differentiation fate, one question is when the cell fate is determinated. To understand whether the cell fate and cell migration pattern will be alternated along with the microenvironment transformation, the traditional transplantation technology was used to replace the anterior PS cells in HH4 host embryo using posterior PS tissue labeled by green fluorescent protein (GFP) in the same stage donor embryo, and then, we tracked the migration trajectory of the GFP-positive cells with fluorescence stereomicroscope after incubation, and eventually verified the cell contribution from the transplants with in situ hybridization and immunocytochemistry. The same experimental strategy applied for posterior PS site replacement in host embryo. We found that the transplanted posterior PS cells to anterior part of streak followed the anterior PS cell migration pattern rather than kept its posterior streak cell migration trajectory, and so did vice versa. In addition, the transplants were involved in the contribution to the subsequent organogenesis as the local PS tissues affirmed by specific expression of myocardial or hematopoietic markers. Therefore, our data strongly suggest that the PS cells still keep stem cell plasticity during gastrulation and the eventual cell fate will depend on the spatial gene expression within local microenvironment along with development. PMID:23382139

Wang, Xiao-Yu; Li, Yan; Ma, Zheng-Lai; Wang, Li-Jing; Chuai, Manli; Münsterberg, Andrea; Geng, Jian-Guo; Yang, Xuesong

2013-03-01

161

Stem Cells in Intraepithelial Neoplasia  

Microsoft Academic Search

\\u000a Tumours are thought to contain a subpopulation of self-renewing stem cells, the so-called cancer stem cells, which maintain the tumour. Moreover, tumours themselves are thought to arise from organ-specific stem cells. In epithelia, transformation of these cells leads to spread of a mutated stem cell clone through the epithelial sheet, leading to the development of a pre-invasive lesion. Barrett’s oesophagus

Nicholas A. Wright

162

Controversies over stem cell research  

Microsoft Academic Search

Much interest and effort has focused on the therapeutic potential of stem cell technology to treat presently intractable diseases. However, this scientific promise has been accompanied by important issues, including ethical hurdles, political policies and dilemmas concerning cell-source selection (embryonic versus adult stem cells). Although the contribution of stem cells to medical research seems enormous, many countries now face complex

Gorka Orive; Rosa M. Hernández; Alicia R. Gascón; Manoli Igartua; José Luis Pedraz

2003-01-01

163

Stem Cells, Cytokines And Their Receptors  

Microsoft Academic Search

Stem cells that have totipotent, pluripotent and multipotent abilities can be divided into two main categories: embryonic stem cells and adult stem cells. Embryonic stem cells originate from the inner cell mass of the blastocyst stage during embryonic development whereas adult stem cells are derived from bone marrow. Stem cells have the ability to differentiate into mature cells or transdifferentiate

Shahrul Hisham; Zainal Ariffin; Rohaya Megat Abdul Wahab; Ismanizan Ismail; Nor Muhammad Mahadi; Zaidah Zainal Ariffin

2005-01-01

164

Stem cell therapy for heart failure.  

PubMed

The last decade has witnessed the publication of a large number of clinical trials, primarily using bone marrow-derived stem cells as the injected cell. Much has been learned through these "first-generation" clinical trials. The considerable advances in our understanding include (1) cell therapy is safe, (2) cell therapy has been modestly effective, (3) the recognition that in humans bone marrow-derived stem cells do not transdifferentiate into cardiomyocytes or new blood vessels (or at least in sufficient numbers to have any effect). The primary mechanism of action for cell therapy is now believed to be through paracrine effects that include the release of cytokines, chemokines, and growth factors that inhibit apoptosis and fibrosis, enhance contractility, and activate endogenous regenerative mechanisms through endogenous circulating or site-specific stem cells. The new direction for clinical trials includes the use of stem cells capable of cardiac lineage, such as endogenous cardiac stem cells. PMID:24595173

Michler, Robert E

2014-01-01

165

Stem Cell Therapy for Heart Failure  

PubMed Central

The last decade has witnessed the publication of a large number of clinical trials primarily using bone marrow-derived stem cells as the injected cell. These “first-generation” clinical trials have advanced our understanding and shown us that (1) cell therapy is safe, (2) cell therapy has been modestly effective, and (3) in humans, bone marrow-derived stem cells do not transdifferentiate into cardiomyocytes or new blood vessels (or at least in sufficient numbers to have any effect). The primary mechanism of action for cell therapy is now believed to be through paracrine effects that include the release of cytokines, chemokines, and growth factors that inhibit apoptosis and fibrosis, enhance contractility, and activate endogenous regenerative mechanisms through endogenous circulating or site-specific stem cells. The new direction for clinical trials includes the use of stem cells capable of cardiac lineage, such as endogenous cardiac stem cells.

2013-01-01

166

Cell cycle synchronization of embryonic stem cells: Effect of serum deprivation on the differentiation of embryonic bodies in vitro  

SciTech Connect

Research on stem-cell transplantation has indicated that the success of transplantation largely depends on synchronizing donor cells into the G0/G1 phase. In this study, we investigated the profile of embryonic stem (ES) cell synchronization and its effect on the formation of embryonic bodies (EBs) using cell culture with serum deprivation. The D3 cell line of ES cells was used, and parameters such as cell proliferation and activity, EB formation, and expression of stage-specific embryonic antigen-1 and Oct-4 were investigated. Results showed that the percentage of G0/G1 stage in serum deprivation culture is significantly higher than that in culture with serum supplementation. Synchronized ES cells can reenter the normal cell cycle successfully after serum supply. EBs formed from synchronized ES cells have higher totipotency capability to differentiate into functional neuronal cells than EBs formed from unsynchronized ES cells. Our study provides a method for ES treatment before cell transplantation that possibly helps to decrease the rate of cell death after transplantation.

Zhang Enming [Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027 (China); Li Xiaolong [Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027 (China); Zhang Shufang [Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027 (China); Chen Liangqiang [Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027 (China); Zheng Xiaoxiang [Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027 (China)]. E-mail: zxx@mail.bme.zju.edu.cn

2005-08-12

167

The effects of peptide modified gellan gum and olfactory ensheathing glia cells on neural stem/progenitor cell fate.  

PubMed

The regenerative capacity of injured adult central nervous system (CNS) tissue is very limited. Specifically, traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory functions below the site of injury, as well as other detrimental complications. A potential regenerative strategy is stem cell transplantation; however, cell survival is typically less than 1%. To improve cell survival, stem cells can be delivered in a biomaterial matrix that provides an environment conducive to survival after transplantation. One major challenge in this approach is to define the biomaterial and cell strategies in vitro. To this end, we investigated both peptide-modification of gellan gum and olfactory ensheathing glia (OEG) on neural stem/progenitor cell (NSPC) fate. To enhance cell adhesion, the gellan gum (GG) was modified using Diels-Alder click chemistry with a fibronectin-derived synthetic peptide (GRGDS). Amino acid analysis demonstrated that approximately 300 nmol of GRGDS was immobilized to each mg of GG. The GG-GRGDS had a profound effect on NSPC morphology and proliferation, distinct from that of NSPCs in GG alone, demonstrating the importance of GRGDS for cell-GG interaction. To further enhance NSPC survival and outgrowth, they were cultured with OEG. Here NSPCs interacted extensively with OEG, demonstrating significantly greater survival and proliferation relative to monocultures of NSPCs. These results suggest that this co-culture strategy of NSPCs with OEG may have therapeutic benefit for SCI repair. PMID:22698724

Silva, Nuno A; Cooke, Michael J; Tam, Roger Y; Sousa, Nuno; Salgado, António J; Reis, Rui L; Shoichet, Molly S

2012-09-01

168

The new stem cell biology.  

PubMed Central

Recent studies have indicated that bone marrow stem cells are capable of generating muscle, cardiac, hepatic, renal, and bone cells. Purified hematopoietic stem cells have generated cardiac and hepatic cells and reversed disease manifestations in these tissues. Hematopoietic stem cells also alter phenotype with cell cycle transit or circadian phase. During a cytokine stimulated cell cycle transit, reversible alterations of differentiation and engraftment occur. Primitive hematopoietic stem cells express a wide variety of adhesion and cytokine receptors and respond quickly with migration and podia extensions on exposure to cytokines. These data suggest an "Open Chromatin" model of stem cell regulation in which there is a fluctuating continuum in the stem cell/progenitor cell compartments, rather than a hierarchical relationship. These observations, along with progress in using low dose treatments and tolerization approaches, suggest many new therapeutic strategies involving stem cells and the creation of a new medical specialty; stemology. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6

Quesenberry, Peter J.; Colvin, Gerald A.; Lambert, Jean-Francois; Frimberger, Angela E.; Dooner, Mark S.; Mcauliffe, Christina I.; Miller, Caroline; Becker, Pamela; Badiavas, Evangelis; Falanga, Vincent J.; Elfenbein, Gerald; Lum, Lawrence G.

2002-01-01

169

Stem cells today: B1. Bone marrow stem cells  

Microsoft Academic Search

This review is the second in a series of four devoted to the analysis of recent studies on stem cells. The first considered embryo stem cells (ES). This review covers bone marrow stem cells. They are analysed initially in a historical perspective, and then in relation to foundation studies in the later 20th century before a detailed analysis is presented

RG Edwards

2004-01-01

170

Effects of antioxidants on the quality and genomic stability of induced pluripotent stem cells.  

PubMed

Effects of antioxidants on the quality and genomic stability of induced pluripotent stem (iPS) cells were investigated with two human iPS cell lines (201B7 and 253G1). Cells used in this study were expanded from a single colony of each cell line with the addition of proprietary antioxidant supplement or homemade antioxidant cocktail in medium, and maintained in parallel for 2 months. The cells grew well in all culture conditions and kept "stemness". Although antioxidants modestly decreased the levels of intracellular reactive oxygen species, there were no differences in the expression of 53BP1 and pATM, two critical molecules related with DNA damage and repair, under various culture conditions. CGH analysis showed that the events of genetic aberrations were decreased only in the 253G1 iPS cells with the addition of homemade antioxidant cocktail. Long-term culture will be necessary to confirm whether low dose antioxidants improve the quality and genomic stability of iPS cells. PMID:24445363

Luo, Lan; Kawakatsu, Miho; Guo, Chao-Wan; Urata, Yoshishige; Huang, Wen-Jing; Ali, Haytham; Doi, Hanako; Kitajima, Yuriko; Tanaka, Takayuki; Goto, Shinji; Ono, Yusuke; Xin, Hong-Bo; Hamano, Kimikazu; Li, Tao-Sheng

2014-01-01

171

[Effect of osteogenically and adipogenically differentiated bone mesenchymal stem cells from mouse on osteoclast formation].  

PubMed

This study was purposed to investigate the regulatory effects of differentiating mesenchymal stem cells (MSC) on osteoclast formation. The MSC from mouse compact bones were cultured and induced into osteoblasts and adipocytes for one week. To test their regulatory effect on osteoclastogenesis, osteogenically differentiated and adipogenically differentiated MSC were co-cultured with CD11b(+) monocytes and osteoclasts were identified with in situ tartrate-resistant acid phosphatase (TRAP) staining. The results showed that differentiated MSC supported osteoclastogenesis but the osteoclast supporting capacity of osteogenically differentiated MSC decreased as compared with undifferentiated MSC. More interestingly, the adipogenically differentiated MSC significantly promoted osteoclasts formation when co-cultured with monocytes. It is concluded that the regulatory effect of MSC on osteoclast formation has changed while they have differentiated into different types of cells. The findings indicate that MSC may exert alternative effect on osteoclastogenesis by differentiation to descendant cells. PMID:23114145

Zhu, Heng; Liu, Yuan-Lin; Chen, Ji-De; Li, Hong; Liu, Yu-Xiao; Xu, Fen-Fen; Jiang, Xiao-Xia; Zhang, Yi; Mao, Ning

2012-10-01

172

Effects of Filipin and Cholesterol on K Movement in Etiolated Stem Cells of Pisum sativum L.  

PubMed

Filipin, a polyene antibiotic known to induce leakage of materials from various cells, depresses K(+) and NO(3) (-) uptake in etiolated pea epicotyl segments. Filipin concentrations which strongly reduce K(+) influx have little effect on efflux; however, high concentrations enhance K(+) efflux. Filipin has no effect on respiration rates or cell electropotentials; its action is presumed to be on the cell membranes. Cholesterol, but not a thiol-protecting agent (dithiothreitol), enhances K(+) influx and counteracts the inhibition by filipin. Although this effect of cholesterol may be due to an interaction with filipin in the outer solution, there is reason to believe that its major effect is to impart stability to the membrane; filipin is believed to act by interfering with sterol stabilization of phospholipid layers. The predominant native sterols of etiolated pea stem (Pisum sativum L. var. Alaska), which cholesterol probably mimics, are beta-sitosterol, campesterol, and stigmasterol. PMID:16658528

Hendrix, D L; Higinbotham, N

1973-08-01

173

Specificity and Heterogeneity of Terahertz Radiation Effect on Gene Expression in Mouse Mesenchymal Stem Cells  

NASA Astrophysics Data System (ADS)

We report that terahertz (THz) irradiation of mouse mesenchymal stem cells (mMSCs) with a single-frequency (SF) 2.52 THz laser or pulsed broadband (centered at 10 THz) source results in irradiation specific heterogenic changes in gene expression. The THz effect depends on irradiation parameters such as the duration and type of THz source, and on the degree of stem cell differentiation. Our microarray survey and RT-PCR experiments demonstrate that prolonged broadband THz irradiation drives mMSCs toward differentiation, while 2-hour irradiation (regardless of THz sources) affects genes transcriptionally active in pluripotent stem cells. The strictly controlled experimental environment indicates minimal temperature changes and the absence of any discernable response to heat shock and cellular stress genes imply a non-thermal response. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.

Alexandrov, Boian S.; Phipps, M. Lisa; Alexandrov, Ludmil B.; Booshehri, Layla G.; Erat, Anna; Zabolotny, Janice; Mielke, Charles H.; Chen, Hou-Tong; Rodriguez, George; Rasmussen, Kim Ø.; Martinez, Jennifer S.; Bishop, Alan R.; Usheva, Anny

2013-01-01

174

Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.  

PubMed

We report that terahertz (THz) irradiation of mouse mesenchymal stem cells (mMSCs) with a single-frequency (SF) 2.52?THz laser or pulsed broadband (centered at 10?THz) source results in irradiation specific heterogenic changes in gene expression. The THz effect depends on irradiation parameters such as the duration and type of THz source, and on the degree of stem cell differentiation. Our microarray survey and RT-PCR experiments demonstrate that prolonged broadband THz irradiation drives mMSCs toward differentiation, while 2-hour irradiation (regardless of THz sources) affects genes transcriptionally active in pluripotent stem cells. The strictly controlled experimental environment indicates minimal temperature changes and the absence of any discernable response to heat shock and cellular stress genes imply a non-thermal response. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression. PMID:23378916

Alexandrov, Boian S; Phipps, M Lisa; Alexandrov, Ludmil B; Booshehri, Layla G; Erat, Anna; Zabolotny, Janice; Mielke, Charles H; Chen, Hou-Tong; Rodriguez, George; Rasmussen, Kim Ø; Martinez, Jennifer S; Bishop, Alan R; Usheva, Anny

2013-01-01

175

Specificity and Heterogeneity of Terahertz Radiation Effect on Gene Expression in Mouse Mesenchymal Stem Cells  

PubMed Central

We report that terahertz (THz) irradiation of mouse mesenchymal stem cells (mMSCs) with a single-frequency (SF) 2.52?THz laser or pulsed broadband (centered at 10?THz) source results in irradiation specific heterogenic changes in gene expression. The THz effect depends on irradiation parameters such as the duration and type of THz source, and on the degree of stem cell differentiation. Our microarray survey and RT-PCR experiments demonstrate that prolonged broadband THz irradiation drives mMSCs toward differentiation, while 2-hour irradiation (regardless of THz sources) affects genes transcriptionally active in pluripotent stem cells. The strictly controlled experimental environment indicates minimal temperature changes and the absence of any discernable response to heat shock and cellular stress genes imply a non-thermal response. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.

Alexandrov, Boian S.; Phipps, M. Lisa; Alexandrov, Ludmil B.; Booshehri, Layla G.; Erat, Anna; Zabolotny, Janice; Mielke, Charles H.; Chen, Hou-Tong; Rodriguez, George; Rasmussen, Kim ?.; Martinez, Jennifer S.; Bishop, Alan R.; Usheva, Anny

2013-01-01

176

Stem Cells and Bioactive Materials  

Microsoft Academic Search

Major advances in biological and materials research have created the possibilities for tissue engineering and regenerative\\u000a medicine. Finding the most effective ways of utilising stem cells, of several types, and triggering their differentiatoin\\u000a in a controlled manner will provide cell sources for cell replacement therapy. Materials will be bioresorbable in vivo and bioactive, contributing to differentiation, implantation and long-term engraftment

Robert C. Bielby; Julia M. Polak

177

Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?  

PubMed Central

Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific “metabolic sign” has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific “metabolic sign” reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined.

Pacini, Nicola; Borziani, Fabio

2014-01-01

178

Cancer stem cell theory and the warburg effect, two sides of the same coin?  

PubMed

Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific "metabolic sign" has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific "metabolic sign" reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined. PMID:24857919

Pacini, Nicola; Borziani, Fabio

2014-01-01

179

Effect of Antibiotics against Mycoplasma sp. on Human Embryonic Stem Cells Undifferentiated Status, Pluripotency, Cell Viability and Growth  

PubMed Central

Human embryonic stem cells (hESCs) are self-renewing pluripotent cells that can differentiate into specialized cells and hold great promise as models for human development and disease studies, cell-replacement therapies, drug discovery and in vitro cytotoxicity tests. The culture and differentiation of these cells are both complex and expensive, so it is essential to extreme aseptic conditions. hESCs are susceptible to Mycoplasma sp. infection, which is hard to detect and alters stem cell-associated properties. The purpose of this work was to evaluate the efficacy and cytotoxic effect of PlasmocinTM and ciprofloxacin (specific antibiotics used for Mycoplasma sp. eradication) on hESCs. Mycoplasma sp. infected HUES-5 884 (H5 884, stable hESCs H5-brachyury promoter-GFP line) cells were effectively cured with a 14 days PlasmocinTM 25 µg/ml treatment (curative treatment) while maintaining stemness characteristic features. Furthermore, cured H5 884 cells exhibit the same karyotype as the parental H5 line and expressed GFP, through up-regulation of brachyury promoter, at day 4 of differentiation onset. Moreover, H5 cells treated with ciprofloxacin 10 µg/ml for 14 days (mimic of curative treatment) and H5 and WA09 (H9) hESCs treated with PlasmocinTM 5 µg/ml (prophylactic treatment) for 5 passages retained hESCs features, as judged by the expression of stemness-related genes (TRA1-60, TRA1-81, SSEA-4, Oct-4, Nanog) at mRNA and protein levels. In addition, the presence of specific markers of the three germ layers (brachyury, Nkx2.5 and cTnT: mesoderm; AFP: endoderm; nestin and Pax-6: ectoderm) was verified in in vitro differentiated antibiotic-treated hESCs. In conclusion, we found that PlasmocinTM and ciprofloxacin do not affect hESCs stemness and pluripotency nor cell viability. However, curative treatments slightly diminished cell growth rate. This cytotoxic effect was reversible as cells regained normal growth rate upon antibiotic withdrawal.

Romorini, Leonardo; Riva, Diego Ariel; Bluguermann, Carolina; Videla Richardson, Guillermo Agustin; Scassa, Maria Elida; Sevlever, Gustavo Emilio; Miriuka, Santiago Gabriel

2013-01-01

180

Effect of sertraline on proliferation and neurogenic differentiation of human adipose-derived stem cells  

PubMed Central

Background: Antidepressant drugs are commonly employed for anxiety and mood disorders. Sertraline is extensively used as antidepressant in clinic. In addition, adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human adipose-derived stem cells (hADSCs) may be useful for autologous transplantation. Materials and Methods: In the present study, we assessed the effect of antidepressant drug Sertraline on the proliferation and neurogenic differentiation of hADSCs using MTT assay and immunofluorescence technique respectively. Results: MTT assay analysis showed that 0.5 ?M Sertraline significantly increased the proliferation rate of hADSCs induced cells (P < 0.05), while immunofluorescent staining indicated that Sertraline treatment during neurogenic differentiation could be decreased the percentage of glial fibrillary acidic protein and Nestin-positive cells, but did not significantly effect on the percentage of MAP2 positive cells. Conclusion: Overall, our data show that Sertraline can be promoting proliferation rate during neurogenic differentiation of hADSCs after 6 days post-induction, while Sertraline inhibits gliogenesis of induced hADSCs.

Razavi, Shahnaz; Jahromi, Maliheh; Amirpour, Nushin; Khosravizadeh, Zahra

2014-01-01

181

Effects of Electromagnetic Fields on Osteogenesis of Human Alveolar Bone-Derived Mesenchymal Stem Cells  

PubMed Central

This study was performed to investigate the effects of extremely low frequency pulsed electromagnetic fields (ELF-PEMFs) on the proliferation and differentiation of human alveolar bone-derived mesenchymal stem cells (hABMSCs). Osteogenesis is a complex series of events involving the differentiation of mesenchymal stem cells to generate new bone. In this study, we examined not merely the effect of ELF-PEMFs on cell proliferation, alkaline phosphatase (ALP) activity, and mineralization of the extracellular matrix but vinculin, vimentin, and calmodulin (CaM) expressions in hABMSCs during osteogenic differentiation. Exposure of hABMSCs to ELF-PEMFs increased proliferation by 15% compared to untreated cells at day 5. In addition, exposure to ELF-PEMFs significantly increased ALP expression during the early stages of osteogenesis and substantially enhanced mineralization near the midpoint of osteogenesis within 2 weeks. ELF-PEMFs also increased vinculin, vimentin, and CaM expressions, compared to control. In particular, CaM indicated that ELF-PEMFs significantly altered the expression of osteogenesis-related genes. The results indicated that ELF-PEMFs could enhance early cell proliferation in hABMSCs-mediated osteogenesis and accelerate the osteogenesis.

Lim, KiTaek; Hexiu, Jin; Kim, Jangho; Seonwoo, Hoon; Cho, Woo Jae; Choung, Pill-Hoon; Chung, Jong Hoon

2013-01-01

182

Breast Stem Cells and Cancer  

Microsoft Academic Search

\\u000a Recent results have increased our understanding of normal stem cells and the signalling pathways which regulate them during\\u000a the development of the mammary gland. Tumours in many tissues are now thought to develop from dysregulated stem cells and\\u000a depend on activated stem cell self-renewal pathways such as Notch for their tumourigenic capacity. These cancer stem cells\\u000a are recognised by specific

G. Farnie; R. B. Clarke

183

Stem Cells in Immortal Hydra  

Microsoft Academic Search

\\u000a Hydra’s potential immortality and extensive capacity to regenerate and self-renew is due to the presence of three distinct stem\\u000a cell lineages: ectodermal and endodermal epithelial stem cells, and interstitial stem cells. Over the last few years, stem\\u000a cells in Hydra became well-defined in cellular terms of their biology. More recently, efforts using the nearly unlimited potential for tissue\\u000a manipulation combined

Thomas C. G. Bosch

184

Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics.  

PubMed

Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients. PMID:23887631

Zheng, X; Naiditch, J; Czurylo, M; Jie, C; Lautz, T; Clark, S; Jafari, N; Qiu, Y; Chu, F; Madonna, M B

2013-01-01

185

Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics  

PubMed Central

Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.

Zheng, X; Naiditch, J; Czurylo, M; Jie, C; Lautz, T; Clark, S; Jafari, N; Qiu, Y; Chu, F; Madonna, M B

2013-01-01

186

Embryonic Stem Cells  

NSDL National Science Digital Library

BioEd Online is an "educational resource for educators, students, and parents" from the Baylor College of Medicine. This is an excellent place to find educational materials and current information in the field of biology. The "Hot Topics" section of this site focus on current events and issues in biology that are "receiving national attention." The controversy surrounding embryonic stem cells, and coverage it receives in news and research publications in the United States and around the world definitely warrants a closer look at this issue. This "Hot Topic" compiled by Joseph Marx, PhD, Nancy Moreno, PhD, and Deanne Erdmann, MS, contains a brief discussion of the stem cell debate, and includes references and links for further reading. Related news articles can be found as well. Be sure to check out the related slide sets for both embryonic stem cells and stem cells. These slide shows are an excellent resource to use in the classroom. Just add the slides you wish to use to your tray and then view or download your slide tray for an instant visual resource.

Erdmann, Deanne; Marx, Joseph; Moreno, Nancy

2006-07-20

187

Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds.  

PubMed

Functional tissue engineering of connective tissues such as the anterior cruciate ligament (ACL) remains a significant clinical challenge, largely due to the need for mechanically competent scaffold systems for grafting, as well as a reliable cell source for tissue formation. We have designed an aligned, polylactide-co-glycolide (PLGA) nanofiber-based scaffold with physiologically relevant mechanical properties for ligament regeneration. The objective of this study is to identify optimal tissue engineering strategies for fibroblastic induction of human mesenchymal stem cells (hMSC), testing the hypothesis that basic fibroblast growth factor (bFGF) priming coupled with tensile loading will enhance hMSC-mediated ligament regeneration. It was observed that compared to the unloaded, as well as growth factor-primed but unloaded controls, bFGF stimulation followed by physiologically relevant tensile loading enhanced hMSC proliferation, collagen production and subsequent differentiation into ligament fibroblast-like cells, upregulating the expression of types I and III collagen, as well as tenasin-C and tenomodulin. The results of this study suggest that bFGF priming increases cell proliferation, while mechanical stimulation of the hMSCs on the aligned nanofiber scaffold promotes fibroblastic induction of these cells. In addition to demonstrating the potential of nanofiber scaffolds for hMSC-mediated functional ligament tissue engineering, this study yields new insights into the interactive effects of chemical and mechanical stimuli on stem cell differentiation. PMID:24267271

Subramony, Siddarth D; Su, Amanda; Yeager, Keith; Lu, Helen H

2014-06-27

188

Pedf & stem cells: niche vs. nurture.  

PubMed

Anti-angiogenic pigment epithelium-derived factor (PEDF) is a multifunctional 50kD secreted glycoprotein emerging as a key factor in stem cell renewal. Characteristics of the stem cell niche can be highly dependent on location, access to the vasculature, oxygen tension and neighboring cells. In the neural stem cell (NSC) niche, specifically the subventricular zone, PEDF actively participates in the self renewal process and promotes stemness by upregulating Notch signaling effectors Hes1 and Hes5. The local vascular endothelial cells and ependymal cells are the likely sources of PEDF for the NSC while mesenchymal and retinal stem cells can actually produce PEDF. The opposing actions of PEDF and VEGF on various cells are recapitulated in the NSC niche. Intraventricular injection of PEDF promotes stem cell renewal, while injection of VEGF prompts differentiation and neurogenesis in the subventricular zone. Enhancing the expression of PEDF in stem cells has promising therapeutic implications. Bone marrow mesenchymal stem cells overexpressing PEDF effectively inhibited pathologic angiogenesis in the murine eye and these same cells suppressed hepatocellular carcinoma growth. As a protein with bioactivities in nearly all normal organ systems, it is likely that PEDF will continue to gain visibility as an essential component in the development and delivery of novel stem cell-based therapies to combat disease. PMID:23517628

Fitchev, Philip; Chung, Chuhan; Plunkett, Beth A; Brendler, Charles B; Crawford, Susan E

2013-03-18

189

The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury  

PubMed Central

The aim of this study was to investigate the effects and mechanisms of mesenchymal stem cells (MSCs) on haematopoietic reconstitution in reducing bone marrow cell apoptosis effects in irradiated mice, and to research the safe and effective dosage of MSCs in mice with total body irradiation (TBI). After BALB/c mice were irradiated with 5.5 Gy cobalt-60 ?-rays, the following were observed: peripheral blood cell count, apoptosis rate, cell cycle, colony-forming unit-granulocyte macrophage (CFU-GM) and colony-forming unit-fibroblast (CFU-F) counts of bone marrow cells and pathological changes in the medulla. The survival of mice infused with three doses of MSCs after 8.0 Gy or 10 Gy TBI was examined. The blood cells recovered rapidly in the MSC groups. The apoptotic ratio of bone marrow cells in the control group was higher at 24 h after radiation. A lower ratio of G0/G1 cell cycle phases and a higher ratio of G2/M and S phases, as well as a greater number of haematopoietic islands and megalokaryocytes in the bone marrow, were observed in the MSC-treated groups. MSCs induced recovery of CFU-GM and CFU-GM and improved the survival of mice after 8 Gy TBI, but 1.5 × 108 kg?1 of MSCs increased mortality. These results indicate that MSCs protected and treated irradiated mice by inducing haematopoiesis and reducing apoptosis. MSCs may be a succedaneous or intensive method of haematopoietic stem cell transplantation under certain radiation dosages, and could provide a valuable strategy for acute radiation syndrome.

Hu, K X; Sun, Q Y; Guo, M; Ai, H S

2010-01-01

190

Materials as stem cell regulators  

NASA Astrophysics Data System (ADS)

The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine.

Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

2014-06-01

191

Materials as stem cell regulators.  

PubMed

The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine. PMID:24845994

Murphy, William L; McDevitt, Todd C; Engler, Adam J

2014-06-01

192

Characterization of amniotic stem cells.  

PubMed

Abstract The amnion membrane is developed from embryo-derived cells, and amniotic cells have been shown to exhibit multidifferentiation potential. These cells represent a desirable source for stem cells for a variety of reasons. However, to date very few molecular analyses of amnion-derived cells have been reported, and efficient markers for isolating the stem cells remain unclear. This paper assesses the characterization of amnion-derived cells as stem cells by examining stemness marker expressions for amnion-derived epithelial cells and mesenchymal cells by flow cytometry, immunocytochemistry, and quantitative PCR. Flow cytometry revealed that amnion epithelial cells expressed CD133, CD 271, and TRA-1-60, whereas mecenchymal cells expressed CD44, CD73, CD90, and CD105. Immunohistochemistry showed that both cells expressed the stemness markers Oct3/4, Sox2, Klf4, and SSEA4. Stemness genes' expression in amnion epithelial cells, mesenchymal cells, fibroblast, bone marrow-derived mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) was compared by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Amnion-derived epithelial cells and mesenchymal cells expressed Oct3/4, Nanog, and Klf4 more than bone marrow-derived MSCs. The sorted TRA1-60-positive cells expressed Oct3/4, Nanog, and Klf4 more than unsorted cells or TRA1-60-negative cells. TRA1-60 can be a marker for isolating amnion epithelial stem cells. PMID:25068631

Koike, Chika; Zhou, Kaixuan; Takeda, Yuji; Fathy, Moustafa; Okabe, Motonori; Yoshida, Toshiko; Nakamura, Yukio; Kato, Yukio; Nikaido, Toshio

2014-08-01

193

Effect of Spiperone on Mesenchymal Multipotent Stromal and Hemopoietic Stem Cells under Conditions of Pulmonary Fibrosis.  

PubMed

The antifibrotic properties of spiperone and its effect on stem and progenitor cells were studied on the model of reversible bleomycin-induced pulmonary fibrosis in C57Bl/6 mice. Spiperone reduced infiltration of the alveolar interstitium and alveolar ducts with inflammatory cells and prevented the growth of the connective tissue in the parenchyma of bleomycin lungs. Apart from anti-inflammatory effect, spiperone suppressed bone marrow hemopoietic cells (CD3, CD45R (B220), Ly6C, Ly6G (Gr1), CD11b (Mac1), TER-119)-, Sca-1+, c-Kit+, CD34- and progenitor hemopoietic cells (granulocyte-erythroid-macrophage-megakaryocytic and granulocyte CFU). Spiperone-induced disturbances of fi brogenesis were paralleled by restoration of endothelial cells in the lung parenchyma, reduction of the number of circulating bone marrow cells and lung mesenchymopoietic cells (mesenchymal multipotent stromal cells (CD31-, CD34-, CD45-, CD44+, CD73+, CD90+, CD106+) and progenitor fi broblast cells), and suppression of multilineage differentiation of multipotent mesenchymal stromal cells (including fi broblast-lineage cells). PMID:24913578

Skurikhin, E G; Khmelevskaya, E S; Ermakova, N N; Pershina, O V; Reztsova, A M; Krupin, V A; Stepanova, I E; Reztsova, V M; Reikhart, D V; Dygai, A M

2014-05-01

194

Microarrays and Stem Cells  

NSDL National Science Digital Library

In this activity, learners use microarray technology to determine which genes are turned on and off at various points in the differentiation of pluripotent stem cells on their way to becoming pancreatic β cells. An introductory PowerPoint, reading, video clip and an animation provide learners with background information needed to interpret the results of a paper microarray simulation. Learners will position cDNA strips on mini-microarrays to discover which genes are expressing, to what degree they are expressing, and which are not. They use these findings to trace the differentiation of embryonic stem cells that give rise to pancreatic β cells and other cell types. The role of growth factors and proximity of other cell types is central to learners understanding how researchers may direct the ultimate fate of stem cells. The value of this in treating diabetes is also discussed. This activity is recommended for learners studying Biology at the High School (honors, IB and AP) or Undergraduate level.

Colvard, Mary

2010-01-01

195

Stem cells find their niche  

Microsoft Academic Search

The concept that stem cells are controlled by particular microenvironments known as 'niches' has been widely invoked. But niches have remained largely a theoretical construct because of the difficulty of identifying and manipulating individual stem cells and their surroundings. Technical advances now make it possible to characterize small zones that maintain and control stem cell activity in several organs, including

Allan Spradling; Daniela Drummond-Barbosa; Toshie Kai

2001-01-01

196

Comparison of allogeneic T cell-depleted peripheral blood stem cell and bone marrow transplantation: effect of stem cell source on short- and long-term outcome  

Microsoft Academic Search

We report the results of a retrospective single-center study comparing engraftment, acute and chronic GVHD, relapse and survival in patients with malignant hematological disorders transplanted with allogeneic peripheral blood stem cells (alloPBSCT, n = 40) or bone marrow cells (alloBMT, n = 42). All transplants were T cell depleted by in vitro incubation with the Campath-1 monoclonal antibody. Primary graft

RMY Barge; RE Brouwer; MFC Beersma; CWJ Starrenburg; AH Zwinderman; G Hale; H Waldmann; GJ den Ottolander; JHF Falkenburg; R Willemze; WE Fibbe

2001-01-01

197

Melanoma Stem Cells  

Microsoft Academic Search

\\u000a The hypothesis that tumor initiation and growth are driven by a subpopulation of malignant cells, that is, cancer stem cells\\u000a (CSCs), has received considerable attention. The CSC concept predicts that the design of novel therapies that ablate CSCs\\u000a or target CSC-specific protumorigenic signaling pathways might result in more durable therapeutic responses in cancer patients\\u000a than those achieved by therapeutic approaches

Tobias Schatton; Markus H. Frank

198

Epidermal stem cell dynamics  

Microsoft Academic Search

Wong and Reiter have explored the possibility that hair follicle stem cells can give rise to basal cell carcinoma (BCC). They\\u000a expressed in mice an inducible human BCC-derived oncogenic allele of Smoothened, SmoM2, under the control of either the cytokeratin 14 (K14) or cytokeratin 15 (K15) promoter. Smoothened encodes a G-protein-coupled receptor protein in the hedgehog pathway, the misregulation of

Maya Sieber-Blum

2011-01-01

199

Biochemistry of epidermal stem cells?  

PubMed Central

Background The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. Scope of review A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. Major conclusions An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. General significance Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells.

Eckert, Richard L.; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan C.; Boucher, Shayne E.; Bickenbach, Jackie R.; Kerr, Candace

2014-01-01

200

[Bioethical challenges of stem cell tourism].  

PubMed

Stem cells have drawn extraordinary attention from scientists and the general public due to their potential to generate effective therapies for incurable diseases. At the same time, the production of embryonic stem cells involves a serious ethical issue concerning the destruction of human embryos. Although adult stem cells and induced pluripotential cells do not pose this ethical objection, there are other bioethical challenges common to all types of stem cells related particularly to the clinical use of stem cells. Their clinical use should be based on clinical trials, and in special situations, medical innovation, both of which have particular ethical dimensions. The media has raised unfounded expectations in patients and the public about the real clinical benefits of stem cells. At the same time, the number of unregulated clinics is increasing around the world, making direct offers through Internet of unproven stem cell therapies that attract desperate patients that have not found solutions in standard medicine. This is what is called stem cells tourism. This article reviews this situation, its consequences and the need for international cooperation to establish effective regulations to prevent the exploitation of patients and to endanger the prestige of legitimate stem cell research. PMID:24448860

Ventura-Juncá, Patricio; Erices, Alejandro; Santos, Manuel J

2013-08-01

201

Normal Stem Cells and Cancer Stem Cells: The Niche Matters  

Microsoft Academic Search

Scientists have tried for decades to understand cancer development in the context of therapeutic strategies. The realization that cancers may rely on ''cancer stem cells'' that share the self-renewal feature of normal stem cells has changed the perspective with regard to new approaches for treating the disease. In this review, we propose that one of the differences between normal stem

Linheng Li; William B. Neaves

202

Therapeutic effect of human umbilical cord mesenchymal stem cells on neonatal rat hypoxic-ischemic encephalopathy.  

PubMed

The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic-ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post-HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic-ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation. PMID:24265136

Zhang, Xinhua; Zhang, Qinfen; Li, Wei; Nie, Dekang; Chen, Weiwei; Xu, Chunxiang; Yi, Xin; Shi, Jinhong; Tian, Meiling; Qin, Jianbing; Jin, Guohua; Tu, Wenjuan

2014-01-01

203

Introduction to Stem Cell Therapy  

PubMed Central

Stem cells have the ability to differentiate into specific cell types. The two defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are two major classes of stem cells: pluripotent that can become any cell in the adult body, and multipotent that are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation and therapeutic applications are discussed. Stem cells have great potential in tissue regeneration and repair but much still needs to be learned about their biology, manipulation and safety before their full therapeutic potential can be achieved.

Biehl, Jesse K.; Russell, Brenda

2014-01-01

204

The effects of lidocaine and procaine on microRNA expression of adipocyte-derived adult stem cells  

PubMed Central

Background The microRNA (miRNA) pathway has emerged as one of the biologic pathways implicated in stem cell regulation. miRNA is a noncoding, single-stranded RNA consisting of 20-25 nucleotides that inhibits the protein production at the step of translation. The molecular effects of lidocaine and procaine on adipose stem cells were investigated by examining RNA expression array. Methods Adipose stem cells were isolated from a prior abdominal liposuction procedure. The human adipose stem cells were cultured and then added to a mixture of 1 ml of culture medium plus 1 ml of 2% lidocaine or 2% procaine for the duration of 30 minutes. The expression levels of miRNAs were estimated by using peptide nucleic acid (PNA)-miRNA array analysis throughout the denaturation and hybridization processes after the isolation of miRNA. The miRNAs detected by microarray that either decreased by half fold or increased by 1.5 fold from the control level were interpreted as significant. Results According to microarray analysis there were 61 miRNAs in total, and no miRNA had decreased expression levels. The stem cells treatment with lidocaine showed 4 alteration of expression with miR-9a* (1.53 fold), miR-29a (1.64 fold), miR-296-5p (1.64 fold) and miR-373 (1.94 fold). The stem cells treated with procaine showed 32 miRNAs that were significantly up-regulated with a range of 1.5 to 2.06 fold. They were stem cell differentiation-related miRNAs, apoptosis and cell cycle-associated miRNAs, immunity-associated miRNAs and hormonal response-related miRNAs. Conclusions Lidocaine and procaine affect the miRNA expression on adipose stem cells and the effect of procaine is more marked than that of lidocaine.

Sung, Sang Hoon; Lee, Jeong Gil; Yu, Soo Bong; Chang, Hee Kyung

2012-01-01

205

Effects of Foeniculum vulgare ethanol extract on osteogenesis in human mecenchymal stem cells  

PubMed Central

Objective: Osteoporosis or silent disease is a major bone disorder in elderly women in current century. Estrogen has an important role in osteogenesis and prevention of bone fractures. Hormone replacement therapy (HRT) is usually accompanied by such effects as breast and ovary cancers. Thus, there is an increasing demand for replacement with plant phytoestrogens. This study is focused on determining the effects of Foeniculum vulgare extract on proliferation and osteogenesis progress in human mesenchymal stem cells. Materials and Methods: Human mesenchymal stem cells were isolated and treated with different amount of plant extracts (0.5 to 100 µg/ml). Extract cytotoxicity was measured using MTT assay. The alkaline phosphatase enzyme activity was measured to evaluate the differentiation progress. Results: Results of MTT assay and alkaline phosphatase activity showed that Foeniculum vulgare extract, at range of 5 to 50 µg/ml, may positively affect cell proliferation and mineralization. The most proliferation and enzyme activity were seen with dose of 5 µg/ml. Conclusions: Foeniculum vulgare has been used in Iranian folk medicine for many years. Our in vitro study showed that Foeniculum vulgare extract has osteoprotective effects.

Mahmoudi, Zahra; Soleimani, Masoud; saidi, Abbas; Khamisipour, Gholamreza; Azizsoltani, Arezoo

2013-01-01

206

Effect of human Wharton's jelly mesenchymal stem cell paracrine signaling on keloid fibroblasts.  

PubMed

Keloid scars are abnormal benign fibroproliferative tumors with high recurrence rates and no current efficacious treatment. Accumulating evidence suggests that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have antifibrotic properties. Paracrine signaling is considered one of the main underlying mechanisms behind the therapeutic effects of mesenchymal stem cells. However, the paracrine signaling effects of WJ-MSCs on keloids have not yet been reported. The aim of this study is to investigate paracrine signaling effects of human WJ-MSCs on keloid fibroblasts in vitro. Human umbilical cords and keloid skin samples were obtained, and WJ-MSCs and keloid fibroblasts were isolated and cultured. One-way and two-way paracrine culture systems between both cell types were investigated. Plasminogen activator inhibitor-I and transforming growth factor-?2 (TGF-?2) transcripts were upregulated in keloid fibroblasts cultured with WJ-MSC-conditioned medium (WJ-MSC-CM) and cocultured with inserts, while showing lower TGF-?3 gene expression. Interleukin (IL)-6, IL-8, TGF-?1, and TGF-?2 protein expression was also enhanced. The WJ-MSC-CM-treated keloid fibroblasts showed higher proliferation rates than their control keloid fibroblasts with no significant change in apoptosis rate or migration ability. In our culture conditions, the indirect application of WJ-MSCs on keloid fibroblasts may enhance their profibrotic phenotype. PMID:24436441

Arno, Anna I; Amini-Nik, Saeid; Blit, Patrick H; Al-Shehab, Mohammed; Belo, Cassandra; Herer, Elaine; Jeschke, Marc G

2014-03-01

207

Human neural stem cells transduced with IFN-? and cytosine deaminase genes intensify bystander effect in experimental glioma  

Microsoft Academic Search

Previously, we have shown that the genetically modified human neural stem cells (NSCs) show remarkable migratory and tumor-tropic capability to track down brain tumor cells and deliver therapeutic agents with significant therapeutic benefit. Human NSCs that were retrovirally transduced with cytosine deaminase (CD) gene showed remarkable ‘bystander killer effect’ on the glioma cells after application of the prodrug, 5-fluorocytosine (5-FC).

S Ito; A Natsume; S Shimato; M Ohno; T Kato; P Chansakul; T Wakabayashi; S U Kim

2010-01-01

208

Human cardiac stem cells  

PubMed Central

The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin.

Bearzi, Claudia; Rota, Marcello; Hosoda, Toru; Tillmanns, Jochen; Nascimbene, Angelo; De Angelis, Antonella; Yasuzawa-Amano, Saori; Trofimova, Irina; Siggins, Robert W.; LeCapitaine, Nicole; Cascapera, Stefano; Beltrami, Antonio P.; D'Alessandro, David A.; Zias, Elias; Quaini, Federico; Urbanek, Konrad; Michler, Robert E.; Bolli, Roberto; Kajstura, Jan; Leri, Annarosa; Anversa, Piero

2007-01-01

209

Human cardiac stem cells.  

PubMed

The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin. PMID:17709737

Bearzi, Claudia; Rota, Marcello; Hosoda, Toru; Tillmanns, Jochen; Nascimbene, Angelo; De Angelis, Antonella; Yasuzawa-Amano, Saori; Trofimova, Irina; Siggins, Robert W; Lecapitaine, Nicole; Cascapera, Stefano; Beltrami, Antonio P; D'Alessandro, David A; Zias, Elias; Quaini, Federico; Urbanek, Konrad; Michler, Robert E; Bolli, Roberto; Kajstura, Jan; Leri, Annarosa; Anversa, Piero

2007-08-28

210

Defining Vascular Stem Cells  

PubMed Central

Mesenchymal stem cells (MSCs) exist in most adult tissues and have been located near or within blood vessels. Although “perivascular” has been commonly used to describe such locations, increasing evidence points at the vessel wall as the exact location. Thus, “vascular stem cells (VSCs)” is recommended as a more accurate term for MSCs. Furthermore, 2 cell populations, namely pericytes and adventitial progenitor cells (APCs), are the likely VSCs. The pericyte evidence relies on the so-called pericyte-specific markers, but none of these markers is pericyte specific. In addition, pericytes appear to be too functionally diverse and sophisticated to have a large differentiation capacity. On the other hand, APCs are more naïve functionally and, therefore, more akin to being VSCs. In vitro, these cells spontaneously differentiate into pericytes, and can be induced to differentiate into vascular cells (endothelial and smooth muscle cells) and mesenchymal cells (eg, bone, cartilage, and fat). In vivo, indirect evidence also points to their ability to differentiate into mesenchymal cells of their native tissue (eg, fat). Moreover, they possess a large paracrine capacity and, therefore, can help maintain tissue homeostasis by encouraging the replication and differentiation of mesenchymal cells locally. These proposed in vivo functions are areas of interest for future research on VSCs.

Lue, Tom F.

2013-01-01

211

Liver stem cells.  

PubMed

The capacity of hepatocytes and cholangiocytes to contribute to their own maintenance has long been recognized. More recently, studies have indicated the presence of both intra-hepatic and extra-hepatic stem/progenitor cell populations. The intraorgan compartment probably derives primarily from the biliary tree, most particularly the most proximal branches, i.e. the canals of Hering and smallest ductules. The extra-organ compartment is at least in part derived from diverse populations of cells from the bone marrow. These three tiers of liver cell regeneration serve to maintain the normal organ and to regenerate damaged parenchyma in response to a variety of insults. The nature and extent of the insult determines the balance between these stem/progenitor compartments. PMID:19002950

Theise, Neil D

2003-03-01

212

Cancer Stem Cells: Hepatocellular Carcinoma  

Microsoft Academic Search

It has been hypothesized that cancer stem cells result from the initiation of normal tissue stem cells by mutagens. These\\u000a cells give rise to a population of growth and differentiation dysregulated transient amplifying cells that represent the bulk\\u000a of the tumor. Fifty years of research has provided a relatively large knowledge base on adult liver stem cells termed “oval\\u000a cells

Thomas Shupe; Bryon E. Petersen

213

Role of mesenchymal stem cells in hematopoietic stem cell transplantation.  

PubMed

Within the bone marrow stroma are multipotential cells which are capable of differentiation into a number of mesenchymal cell lineages. These cells, termed mesenchymal stem cells, have recently been identified and characterized in humans. Many studies indicate that the bone marrow stroma is damaged following bone marrow transplantation. Since the marrow stroma is critical for the maintenance of hematopoiesis, its ability to support hematopoiesis following stem cell transplantation may be impaired. Animal models suggest that the transplantation of healthy stromal elements, including mesenchymal stem cells, may enhance the ability of the bone marrow microenvironment to support hematopoiesis after stem cell transplantation. Here the authors review recent data that suggest that mesenchymal stem cells may possess therapeutic value not only for the repair of damaged mesenchymal tissues following hematopoietic stem cell transplantation, but also as potential vectors for the delivery of corrective genes. PMID:11055509

Devine, S M; Hoffman, R

2000-11-01

214

Effective Elimination of Cancer Stem Cells by a Novel Drug Combination Strategy  

PubMed Central

Development of effective therapeutic strategies to eliminate Cancer stem cells (CSCs), which play a major role in drug resistance and disease recurrence, is critical to improve cancer treatment outcomes. Our study showed that glioblastoma stem cells (GSCs) exhibited low mitochondrial respiration and high glycolytic activity. These GSCs were highly resistant to standard drugs such as carmustine and temozolomide, but showed high sensitivity to a glycolytic inhibitor 3-bromo-2-oxopropionate-1-propyl ester (3-BrOP), especially under hypoxic conditions. We further showed that combination of 3-BrOP with carmustine but not with temozolomide achieved a striking synergistic effect and effectively killed GSCs through a rapid depletion of cellular ATP and inhibition of carmustine-induced DNA repair. This drug combination significantly impaired the sphere formation ability of GSCs in vitro and tumor formation in vivo, leading to increase in the overall survival of mice bearing orthotopic inoculation of GSCs. Further mechanistic study showed that 3-BrOP and carmustine inhibited glyceraldehyde-3-phosphate dehydrogenase and caused a severe energy crisis in GSCs. Our study suggests that GSCs are highly glycolytic and that certain drug combination strategies can be used to effectively overcome their drug resistance based on their metabolic properties.

Yuan, Shuqiang; Wang, Feng; Chen, Gang; Zhang, Hui; Feng, Li; Wang, Lei; Colman, Howard; Keating, Michael J.; Li, Xiaonan; Xu, Rui-Hua; Wang, Jianping; Huang, Peng

2012-01-01

215

Effective elimination of cancer stem cells by a novel drug combination strategy.  

PubMed

Development of effective therapeutic strategies to eliminate cancer stem cells, which play a major role in drug resistance and disease recurrence, is critical to improve cancer treatment outcomes. Our study showed that glioblastoma stem cells (GSCs) exhibited low mitochondrial respiration and high glycolytic activity. These GSCs were highly resistant to standard drugs such as carmustine and temozolomide (TMZ), but showed high sensitivity to a glycolytic inhibitor 3-bromo-2-oxopropionate-1-propyl ester (3-BrOP), especially under hypoxic conditions. We further showed that combination of 3-BrOP with carmustine but not with TMZ achieved a striking synergistic effect and effectively killed GSCs through a rapid depletion of cellular ATP and inhibition of carmustine-induced DNA repair. This drug combination significantly impaired the sphere-forming ability of GSCs in vitro and tumor formation in vivo, leading to increase in the overall survival of mice bearing orthotopic inoculation of GSCs. Further mechanistic study showed that 3-BrOP and carmustine inhibited glyceraldehyde-3-phosphate dehydrogenase and caused a severe energy crisis in GSCs. Our study suggests that GSCs are highly glycolytic and that certain drug combination strategies can be used to effectively overcome their drug resistance based on their metabolic properties. PMID:23132831

Yuan, Shuqiang; Wang, Feng; Chen, Gang; Zhang, Hui; Feng, Li; Wang, Lei; Colman, Howard; Keating, Michael J; Li, Xiaonan; Xu, Rui-Hua; Wang, Jianping; Huang, Peng

2013-01-01

216

Therapeutic effects of stem cell on hyperglycemia, hyperlipidemia, and oxidative stress in alloxan-treated rats.  

PubMed

Diabetes mellitus is the most common endocrine disorder that affects more than 285 million people worldwide. The purpose of this study was to investigate the effect of mesenchymal stem cells (MSCs) from the bone marrow of albino rats, on hyperglycemia, hyperlipidemia, and oxidative stress induced by intraperitoneal injection (i.p.) of alloxan at a dose of 150 mg/kg in rats. Injection of alloxan into rats resulted in a significant increase in serum glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, and sialic acid level and a significant decrease in serum insulin, high density lipoprotein-cholesterol, vitamin E, and liver glycogen as compared to their corresponding controls. Also, oxidative stress was noticed in pancreatic tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Treatment of diabetic rats with MSCs stem cells significantly prevented these alterations and attenuated alloxan-induced oxidative stress. In conclusion, rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats. This may be helpful in the prevention of diabetic complications associated with oxidative stress. PMID:24604673

El-Tantawy, Walid Hamdy; Haleem, Ekram Nemr Abd Al

2014-06-01

217

[Stem cells of dental pulp].  

PubMed

Any clinician dreams to obtain the regeneration of the destroyed organ for his patient. In the human being, the regeneration of complex structures is not possible, except the liver and the bone marrow, which can be regenerated because of the presence of adult stem cells in these tissues. The stem cells have two principal properties: they ensure their self-renewal and they have the ability to differentiate into several cellular types. Using specific markers allowing the identification of the stem cells in bone marrow, stem cells were observed in dental pulp tissues. Although the origin, the identification, and the localization of these stem cells of dental pulp remain under consideration, the optimism in research on stem cells permits to believe that the knowledge on dental stem cells will lead to their use in therapeutics. PMID:17720580

Renard, Emmanuelle; Lopez-Cazaux, Séréna; Guicheux, Jérome; Weiss, Pierre; Laboux, Olivier; Alliot-Licht, Brigitte

2007-09-01

218

Physiologic hypoxia promotes maintenance of CML stem cells despite effective BCR-ABL1 inhibition.  

PubMed

C-abl oncogene 1, nonreceptor tyrosine kinase (ABL1) kinase inhibitors such as imatinib mesylate (imatinib) are effective in managing chronic myeloid leukemia (CML) but incapable of eliminating leukemia stem cells (LSCs), suggesting that kinase-independent pathways support LSC survival. Given that the bone marrow (BM) hypoxic microenvironment supports hematopoietic stem cells, we investigated whether hypoxia similarly contributes to LSC persistence. Importantly, we found that although breakpoint cluster region (BCR)-ABL1 kinase remained effectively inhibited by imatinib under hypoxia, apoptosis became partially suppressed. Furthermore, hypoxia enhanced the clonogenicity of CML cells, as well as their efficiency in repopulating immunodeficient mice, both in the presence and absence of imatinib. Hypoxia-inducible factor 1 ? (HIF1-?), which is the master regulator of the hypoxia transcriptional response, is expressed in the BM specimens of CML individuals. In vitro, HIF1-? is stabilized during hypoxia, and its expression and transcriptional activity can be partially attenuated by concurrent imatinib treatment. Expression analysis demonstrates at the whole-transcriptome level that hypoxia and imatinib regulate distinct subsets of genes. Functionally, knockdown of HIF1-? abolished the enhanced clonogenicity during hypoxia. Taken together, our results suggest that in the hypoxic microenvironment, HIF1-? signaling supports LSC persistence independent of BCR-ABL1 kinase activity. Thus, targeting HIF1-? and its pathway components may be therapeutically important for the complete eradication of LSCs. PMID:24705490

Ng, King Pan; Manjeri, Aditi; Lee, Kian Leong; Huang, Weijie; Tan, Soo Yong; Chuah, Charles T H; Poellinger, Lorenz; Ong, S Tiong

2014-05-22

219

Effects of high glucose on mesenchymal stem cell proliferation and differentiation.  

PubMed

High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase-immortalized MSC (hMSC-TERT) and primary MSC (hMSC). HG (25mM) enhanced hMSC-TERT proliferation in long-term studies in contrast to hMSC where proliferation was unchanged. Thioredoxin-interacting protein, which is involved in apoptosis regulation, was stimulated by glucose in hMSC-TERT. However, apoptosis was not influenced by HG in both cell types. MSC treatment with HG favored osteogenic differentiation. MSC are resistant to HG toxicity, depending on the stemness of MSC. Proliferation and osteogenic differentiation are stimulated by HG. Effects of HG on the transient amplifying compartment of MSC may differ from those in mature cells. Further research is needed to unravel the molecular mechanisms of HG resistance of MSC. PMID:17868648

Li, Yu-Ming; Schilling, Tatjana; Benisch, Peggy; Zeck, Sabine; Meissner-Weigl, Jutta; Schneider, Doris; Limbert, Catarina; Seufert, Jochen; Kassem, Moustapha; Schütze, Norbert; Jakob, Franz; Ebert, Regina

2007-11-01

220

Effects of adipose stem cell-conditioned medium on the migration of vascular endothelial cells, fibroblasts and keratinocytes  

PubMed Central

Adipose stem cell-conditioned medium (ASC-CM) has been successfully used to treat multiple types of tissue and organ defects, including skin wounds both in vitro and in vivo. However, the mechanisms through which ASC-CM promotes wound healing remain unclear. We hypothesized that the wound healing effect of ASC-CM is mediated in part by the promotion of the migration of vascular endothelial cells, fibroblasts and keratinocytes, the three cell types essential for wound healing. We reported that ASC-CM stimulated the migration of these cells sequentially, and endothelial cells were the first cell type to respond to ASC-CM stimulation (4 h), followed by fibroblasts (12 h) and then keratinocytes (24 h). We also determined the optimal concentration of ASC-CM in stimulating these cells (50% dilution) in addition to the optimal time to intervene in order to maximize the wound healing activity of ASC-CM. Our data suggest an important role for ASC-CM in wound healing, possibly through the synthetic action of multiple adipose stem cell-derived cytokines that in turn promote cell migration. Thus, ASC-CM appears to have significant potential in wound healing applications.

HU, LI; ZHAO, JIAJIA; LIU, JIARONG; GONG, NIYA; CHEN, LILI

2013-01-01

221

Effect of acetaminophen and nonsteroidal anti-inflammatory drugs on gene expression of mesenchymal stem cells.  

PubMed

We have previously shown that mesenchymal stem cells (MSCs) from patients with osteoarthritis (OA) constitutively express type X collagen, a marker of late-stage chondrocyte hypertrophy, osteogenic marker genes, including alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), and chondrogenesis marker gene aggrecan (ACAN). As patients with arthritis often take nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (Acet), the purpose of the study was to assess whether these drugs can affect the gene expression of human MSCs. MSCs isolated from the bone marrow of patients with OA or normal donors were cultured without (control) or with Acet or NSAIDs, which include ibuprofen, diclofenac (Dic), naproxen, and celebrex. After 3 days of culture, the expression of type X collagen alpha 1 (COL10A1), ACAN, COL1A1, as well as ALP, BSP, OC, and Runt-related transcription factor 2 was analyzed by real-time reverse transcription (RT)-polymerase chain reaction. The results showed that COL10A1 and the osteogenic and chondrogenic marker genes can be regulated by NSAIDs and Acet in normal MSCs. In contrast, Acet did not significantly affect COL10A1 expression in OA MSCs, while Dic is the only drug that had no significant effect on all markers in normal MSCs. The upregulation of COL10A1 in normal MCSs by Acet and Npx may explain why stem cells from patients with OA express COL10A1 constitutively. This knowledge may help in designing better strategies for stem cell differentiation into chondrocyte-like cells, from this source, with Dic being a viable option for treating OA pain, with an eye toward preventing the potential to enhance calcification in the repair of cartilage and degenerated intervertebral discs. PMID:23231452

Almaawi, Abdulaziz; Wang, Hong Tian; Ciobanu, Ovidiu; Rowas, Sora A L; Rampersad, Sonia; Antoniou, John; Mwale, Fackson

2013-04-01

222

Effects of sildenafil and/or muscle derived stem cells on myocardial infarction  

PubMed Central

Background Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i) counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC) exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI cardiac repair than each treatment separately. We have now investigated whether sildenafil at lower doses and MDSC, alone or in combination are effective to attenuate LV remodeling after MI in rats. Methods MI was induced in rats by ligature of the left anterior descending coronary artery. Treatment groups were: “Series A”: 1) untreated; 2) oral sildenafil 3?mg/kg/day from day 1; and “Series B”: intracardiac injection at day 7 of: 3) saline; 4) rat MDSC (106 cells); 5) as #4, with sildenafil as in #2. Before surgery, and at 1 and 4?weeks, the left ventricle ejection fraction (LVEF) was measured. LV sections were stained for collagen, myofibroblasts, apoptosis, cardiomyocytes, and iNOS, followed by quantitative image analysis. Western blots estimated angiogenesis and myofibroblast accumulation, as well as potential sildenafil tachyphylaxis by PDE 5 expression. Zymography estimated MMPs 2 and 9 in serum. Results As compared to untreated MI rats, sildenafil improved LVEF, reduced collagen, myofibroblasts, and circulating MMPs, and increased cardiac troponin T. MDSC replicated most of these effects and stimulated cardiac angiogenesis. Concurrent MDSC/sildenafil counteracted cardiomyocyte and endothelial cells loss, but did not improve LVEF or angiogenesis, and upregulated PDE 5. Conclusions Long-term oral sildenafil, or MDSC given separately, reduce the MI fibrotic scar and improve left ventricular function in this rat model. The failure of the treatment combination may be due to inducing overexpression of PDE5.

2012-01-01

223

Stem cell recovering effect of copper-free GHK in skin.  

PubMed

The peptide Gly-His-Lys (GHK) is a naturally occurring copper(II)-chelating motifs in human serum and cerebrospinal fluid. In industry, GHK (with or without copper) is used to make hair and skin care products. Copper-GHK plays a physiological role in the process of wound healing and tissue repair by stimulating collagen synthesis in fibroblasts. We also reported that copper-GHK promotes the survival of basal stem cells in the skin. However, the effects of copper-free GHK (GHK) have not been investigated well. In this study, the effects of GHK were studied using cultured normal human keratinocytes and skin equivalent (SE) models. In monolayer cultured keratinocytes, GHK increased the proliferation of keratinocytes. When GHK was added during the culture of SE models, the basal cells became more cuboidal than control model. In addition, there was linear and intense staining of ?6 and ?1 integrin along the basement membrane. The number of p63 and proliferating cell nuclear antigen positive cells was also significantly increased in GHK-treated SEs than in control SEs. Western blot and slide culture experiment showed that GHK increased the expression of integrin by keratinocytes. All these results showed that GHK increased the stemness and proliferative potential of epidermal basal cells, which is associated with increased expression of integrin. In conclusion, copper-free GHK showed similar effects with copper-GHK. Thus, it can be said that copper-free GHK can be used in industry to obtain the effects of copper-GHK in vivo. Further study is necessary to explore the relationship between copper-free GHK and copper-GHK. PMID:23019153

Choi, Hye-Ryung; Kang, Youn-A; Ryoo, Sun-Jong; Shin, Jung-Won; Na, Jung-Im; Huh, Chang-Hun; Park, Kyoung-Chan

2012-11-01

224

Effect of bone marrow mesenchymal stem cells on hepatocellular carcinoma in microcirculation.  

PubMed

This study aims t explore the effect and application of bone marrow mesenchymal stem cells (BMSCs) on hepatocellular carcinoma in microcirculation by observing the angiogenesis of hepatocellular carcinoma in transplanted area. BMSCs were isolated and cultured primarily using the method of whole bone marrow culture and identifying surface antigens of third-generation bone marrow-derived mesenchymal stem cells using flow cytometry. Hepatoma cells cultured with BMSCs-conditioned medium (BMSCs-CM) were assayed using the cell proliferation rate of the MTT method. Nude mice were divided into control group (group A), BMSCs cell transplantation group (group B), HepG-2 cell group (group C), and combined BMSCs and HepG-2 cell cotransplanted group (group D). The result showed that the microvascular density was not significantly different in groups A and B. However, the microvascular density at 14 days was higher than 0 day in group C (P < 0.05). In group D, the microvascular density at 14 days was higher than that of 7 and 0 days (P < 0.05) and 7 days was higher than 0 days (P < 0.05). It was showed that the microvascular density did not get significant difference at 0 and 7 days in the four groups (P > 0.05). But the microvascular density of group C was higher than groups A and B at 14 days (P < 0.05), group D was higher than groups A and B at 14 days (P < 0.05) and group D was higher than group C at 14 days (P < 0.05). BMSCs could promote the growth of microvascular in hepatoma cells in a transplanted area. PMID:23584896

Gong, Peng; Wang, Yingxin; Wang, Yulin; Jin, Shi; Luo, Haifeng; Zhang, Jing; Bao, Haidong; Wang, Zhongyu

2013-08-01

225

Marrow Stromal Mesenchymal Stem Cells  

Microsoft Academic Search

\\u000a The broad definition of a stem cell is a population of cells that has the ability to self-renew and to differentiate into\\u000a one or more types of specialized terminally differentiated cells. It has become evident that stem cells persist in and can\\u000a be isolated from many organs postnatally. Stem cells isolated from various sources have been demonstrated to vary in

Cynthia B. Ripoll; Bruce A. Bunnell

226

Immune Responses to Stem Cells and Cancer Stem Cells  

Microsoft Academic Search

\\u000a The demonstrated capacity and potential of pluripotent stem cells to repair the damaged tissues holds great promise in development\\u000a of novel cell replacement therapeutics for treating various chronic and degenerative diseases. However, previous reports show\\u000a that stem cell therapy, in autologous and allogeneic settings, triggers immune responses to stem cells as shown by lymphocyte\\u000a infiltration and inflammation. Therefore, an important

Xiao-Feng Yang; Hong Wang

227

The effects of space flight and microgravity on the growth and differentiation of PICM-19 pig liver stem cells  

Microsoft Academic Search

The PICM-19 pig liver stem cell line was cultured in space for nearly 16 d on the STS-126 mission to assess the effects of\\u000a spaceflight on the liver’s parenchymal cells—PICM-19 cells to differentiate into either monolayers of fetal hepatocytes or\\u000a 3-dimensional bile ductules (cholangiocytes). Semi-quantitative data included light microscopic assessments of final cell\\u000a density, cell morphology, and response to glucagon stimulation

Neil C. Talbot; Thomas J. Caperna; LeAnn Blomberg; Paul G. Graninger; Louis S. Stodieck

2010-01-01

228

The Effects of Zoledronic Acid in the Bone and Vasculature Support of Hematopoietic Stem Cell Niches  

PubMed Central

Hematopoietic stem cells (HSC) are maintained in a tightly regulated bone microenvironment constituted by a rich milieu of cells. Bone cells such as osteoblasts are associated with niche maintenance as regulators of the endosteal microenvironment. Bone remodeling also plays a role in HSC mobilization although it is poorly defined. The effects of zoledronic acid (ZA), a potent bisphosphonate that inhibits bone resorption, were investigated on bone marrow cell populations focusing on HSCs, and the endosteal and vascular niches in bone. ZA treatment significantly increased bone volume and HSCs in both young and adult mice (4 week and 4 month old, respectively). ZA increased vessel numbers with no overall change in vascular volume in bones of young and had no effect on vasculature in adult mice. Since both young and adult mice had increased HSCs and bone mass with differing vasculature responses, this suggests that ZA indirectly supports HSCs via the osteoblastic niche and not the vascular niche. Additionally, gene expression in Lin- cells demonstrated increased expression of self-renewal-related genes Bmi1 and Ink4a suggesting a role of ZA in the modulation of cell commitment and differentiation toward a long-term self-renewing cell. Genes that support the osteoblastic niche, BMP2 and BMP6 were also augmented in ZA treated mice. In conclusion, ZA-induced HSC expansion occurs independent of the vascular niche via indirect modulation of the osteoblastic niche.

Soki, Fabiana N.; Li, Xin; Berry, Janice; Koh, Amy; Sinder, Benjamin P.; Qian, Xu; Kozloff, Kenneth M.; Taichman, Russell S.; McCauley, Laurie K.

2013-01-01

229

Cytotoxic effects of acrylonitrile on human umbilical cord mesenchymal stem cells in vitro.  

PubMed

The effects of acrylonitrile (ACN) on human umbilical cord mesenchymal stem cells (hUC?MSCs) remain unknown. The proliferation, differentiation, clonogenicity and apoptosis effects of ACN and/or N?acetyl?L?cysteine (NAC) on hUC?MSCs were investigated. The results showed that although ACN at a concentration of 0.1 µg/ml did not affect proliferation or the morphology of hUC?MSCs compared with the control, osteogenic differentiation and the positive rate of alkaline phosphatase staining in the experimental group were significantly lower compared with the control (P<0.01). All of the effects of ACN were counteracted using NAC, a typical antioxidant. Using a flow cytometry assay, it was observed that ACN induced apoptosis in hUC?MSCs. The results indicated that the toxic effect produced by ACN on hUC?MSCs is based on a redox mechanism. PMID:24248151

Sun, Xiaochun; Sun, Min; Xie, Yan; Zhai, Wei; Zhu, Wei; Ma, Rui; Lu, Rongzhu; Xu, Wenrong

2014-01-01

230

Effect of human umbilical cord blood mesenchymal stem cell transplantation on neuronal metabolites in ischemic rabbits  

PubMed Central

Background Because there is little research on the effects of transplanted stem cells on neuronal metabolites in infarct areas, we transplanted human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into cerebral ischemic rabbits and examined the neuronal metabolites. Results Rabbits (n?=?40) were equally divided into sham, middle cerebral artery occlusion (MCAO), hUCB-MSC, and saline groups. The rabbit ischemic model was established by MCAO. The effects of hUCB-MSC transplantation were assessed by proton magnetic resonance spectroscopy (1H-MRS), neurological severity scores (NSSs), infarct area volume, neuronal density, and optical density (OD) of microtubule-associated protein 2 (MAP2)-positive cells. We also evaluated complete blood cell counts(CBCs) and serum biochemical parameters. NSSs in the hUCB-MSC group at 7 and 14 days after reperfusion were lower than in MCAO and saline groups (p?cells in the MCAO group were significantly lower than those in the sham group, whereas the neuronal density and OD of MAP2-positive cells in the hUCB-MSC group were higher than those in MCAO and saline groups (p?stem cells. No significant changes were observed in CBCs or serum biochemical parameters, suggesting that intravenous infusion of hUCB-MSCs is safe for rabbits in the short-term.

2014-01-01

231

Endometrial reconstruction from stem cells.  

PubMed

Adult stem cells have been identified in the highly regenerative human endometrium on the basis of their functional attributes. They can reconstruct endometrial tissue in vivo suggesting their possible use in treating disorders associated with inadequate endometrium. The identification of specific markers for endometrial mesenchymal stem cells and candidate markers for epithelial progenitor cells enables the potential use of endometrial stem/progenitor cells in reconstructing endometrial tissue in Asherman syndrome and intrauterine adhesions. PMID:22657248

Gargett, Caroline E; Ye, Louie

2012-07-01

232

Regenerative Medicine for the Kidney: Renotropic Factors, Renal Stem/Progenitor Cells, and Stem Cell Therapy  

PubMed Central

The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.

Maeshima, Akito; Nojima, Yoshihisa

2014-01-01

233

Stem cells in the eye  

Microsoft Academic Search

In the adult organism, all tissue renewal and regeneration depends ultimately on somatic stem cells, and the eye is no exception. The importance of limbal stem cells in the maintenance of the corneal epithelium has long been recognised, and such cells are now used clinically for repair of a severely damaged cornea. The slow cycling nature of lens epithelial cells

Mike Boulton; Julie Albon

2004-01-01

234

Photoinhibition of stem elongation by blue and red light: effects on hydraulic and cell wall properties  

NASA Technical Reports Server (NTRS)

The underlying mechanism of photoinhibition of stem elongation by blue (BL) and red light (RL) was studied in etiolated seedlings of pea (Pisum sativum L. cv Alaska). Brief BL irradiations resulted in fast transient inhibition of elongation, while a delayed (lag approximately 60 minutes) but prolonged inhibition was observed after brief RL. Possible changes in the hydraulic and wall properties of the growing cells during photoinhibition were examined. Cell sap osmotic pressure was unaffected by BL and RL, but both irradiations increased turgor pressure by approximately 0.05 megapascal (pressure-probe technique). Cell wall yielding was analyzed by in vivo stress relaxation (pressure-block technique). BL and RL reduced the initial rate of relaxation by 38 and 54%, while the final amount of relaxation was decreased by 48 and 10%, respectively. These results indicate that RL inhibits elongation mainly by lowering the wall yield coefficient, while most of the inhibitory effect of BL was due to an increase of the yield threshold. Mechanical extensibility of cell walls (Instron technique) was decreased by BL and RL, mainly due to a reduction in the plastic component of extensibility. Thus, photoinhibitions of elongation by both BL and RL are achieved through changes in cell wall properties, and are not due to effects on the hydraulic properties of the cell.

Kigel, J.; Cosgrove, D. J.

1991-01-01

235

Effects of the EVCAM chemical validation library on differentiation using marker gene expression in lmouse embryonic stem cells  

EPA Science Inventory

The adherent cell differentiation and cytotoxicity (ACDC) assay was used to profile the effects of the ECVAM EST validation chemical library (19 compounds) on J1 mouse embryonic stem cells (mESC). PCR-based TaqMan Low Density Arrays (TLDA) provided a high-content assessment of al...

236

IFN-?-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway  

PubMed Central

Mesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-? would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN-? gene under the control of the EF1? promoter. The IFN-?-modified MSCs effectively secreted functional IFN-?, which led to long-term expression of TRAIL. More importantly, the IFN-?-modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN-?-modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN-?-modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN-?-modified MSCs.

Yang, Xinyuan; Du, Jingchun; Xu, Xia; Xu, Chun; Song, Wu

2014-01-01

237

Manifestations and mechanisms of stem cell aging  

PubMed Central

Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell–based therapy of age-related diseases.

Liu, Ling

2011-01-01

238

Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.  

PubMed

In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ? 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior. PMID:22972165

Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

2013-09-01

239

Regenerative effects of adipose-tissue-derived stem cells for treatment of peripheral nerve injuries.  

PubMed

Peripheral nerve injuries are a common occurrence affecting the nerves found outside the central nervous system. Complete nerve transections necessitate surgical re-anastomosis, and, in cases where there is a significant gap between the two ends of the injured nerve, bridging strategies are required to repair the defect. The current clinical gold standard is the nerve graft, but this has a number of limitations, including donor site morbidity. An active area of research is focused on developing other techniques to replace these grafts, by creating tubular nerve-guidance conduits from natural and synthetic materials, which are often supplemented with biological cues such as growth factors and regenerative cells. In the present short review, we focus on the use of adipose-tissue-derived stem cells and the possible mechanisms through which they may exert a positive influence on peripheral nerve regeneration, thereby enabling more effective nerve repair. PMID:24849239

Kolar, Mallappa K; Kingham, Paul J

2014-06-01

240

Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population.  

PubMed

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer. PMID:21603625

Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

2011-01-01

241

Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population  

PubMed Central

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

2011-01-01

242

Autophagic control of cell 'stemness'  

PubMed Central

Stem cells have the ability to self-renew and differentiate into various cell types. Both cell-intrinsic and extrinsic factors may contribute to aging-related decline in stem cell function and loss of stemness. The maintenance of cellular homeostasis requires timely removal of toxic proteins and damaged organelles that accumulate with age or in pathological conditions. Autophagy is one of the main strategies to eliminate unwanted cytoplasmic materials thereby ultimately preventing cellular damage. Here, we shall discuss the accumulating evidence suggesting that autophagy plays a critical role in the homeostatic control of stem cell functions during aging, tissue regeneration, and cellular reprogramming.

Pan, Huize; Cai, Ning; Li, Mo; Liu, Guang-Hui; Izpisua Belmonte, Juan Carlos

2013-01-01

243

CD11c+ Cells Partially Mediate the Renoprotective Effect Induced by Bone Marrow-Derived Mesenchymal Stem Cells  

PubMed Central

Previous studies have shown that induction of immune tolerance by mesenchymal stem cells (MSCs) is partially mediated via monocytes or dendritic cells (DCs). The purpose of this study was to determine the role of CD11c+ cells in MSC-induced effects on ischemia/reperfusion injury (IRI). IRI was induced in wildtype (WT) mice and CD11c+-depleted mice following pretreatment with or without MSCs. In the in-vitro experiments, the MSC-treated CD11c+ cells acquired regulatory phenotype with increased intracellular IL-10 production. Although splenocytes cocultured with MSCs showed reduced T cell proliferation and expansion of CD4+FoxP3+ regulatory T cells (Tregs), depletion of CD11c+ cells was associated with partial loss of MSCs effect on T cells. In in-vivo experiment, MSCs’ renoprotective effect was also associated with induction of more immature CD11c+ cells and increased FoxP3 expression in I/R kidneys. However all these effects induced by the MSCs were partially abrogated when CD11c+ cells were depleted in the CD11c+-DTR transgenic mice. In addition, the observation that adoptive transfer of WT CD11c+ cells partially restored the beneficial effect of the MSCs, while transferring IL-10 deficient CD11c+ cells did not, strongly suggest the important contribution of IL-10 producing CD11c+ cells in attenuating kidney injury by MSCs. Our results suggest that the CD11c+ cell-Tregs play critical role in mediating renoprotective effect of MSCs.

Kim, Myung-Gyu; Kim, Su Hee; Noh, Hyunjin; Ko, Yoon Sook; Lee, Hee Young; Jo, Sang-Kyung; Cho, Won Yong; Kim, Hyoung Kyu

2013-01-01

244

Effect of glucose concentration during embryoid body (EB) formation from mouse embryonic stem cells on EB growth and cell differentiation.  

PubMed

Embryoid body (EB) formation is an important step in the differentiation of pluripotent stem cells. Although glucose concentration is physiologically maintained at 5.5mM (low glucose; LG) in vivo, a medium containing 25 mM glucose (high glucose; HG) has been widely used for forming EBs in vitro. In this study, we investigated the effect of glucose concentration during EB formation from mouse embryonic stem (ES) cells on EB growth and cell differentiation. EBs were formed under various glucose concentrations: 40, 25, 5.5, and 0mM. Cells aggregated to form EBs regardless of glucose concentration, but 0mM glucose was not appropriate for supporting EB growth as compared with 25 mM glucose. The EBs that formed in the presence of 5.5mM glucose (LG-EBs) were similar both in terms of appearance and decreased expression levels of undifferentiated-ES-cell-marker genes to the EBs that formed in the presence of 25 mM glucose (HG-EBs). However, there was a difference in the propensity for cell differentiation between LG-EBs and HG-EBs. In directed differentiation cultures of EBs into cardiomyocytes and neuronal cells, the HG-EBs more efficiently generated beating cardiac muscle, and the LG-EBs more specifically generated ?III-tubulin-positive cells. These findings demonstrate that the high-glucose (25 mM) condition was not necessary for EB formation in mouse ES cells, whereas the glucose concentration during EB formation affects the propensity for cell differentiation in the attachment cultures of formed EBs. The physiological low-glucose (5.5mM) condition was suitable for forming EBs directed toward neuronal cell differentiation in mouse ES cells. PMID:20869914

Mochizuki, Hidemi; Ohnuki, Yoshitsugu; Kurosawa, Hiroshi

2011-01-01

245

A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons  

PubMed Central

Valproic acid (VPA) is a branched-chain saturated fatty acid with a long history of clinical use as an antiepileptic drug (AED). VPA is also known to inhibit histone deacetylases (HDACs) and to cause diverse effects on neural progenitor cells (NPCs) and neurons. Although the neuroprotective or neurodestructive effects of VPA have been investigated in heterogeneous cell populations, in this study, we used homogeneous populations of NPCs and glutamatergic cortical pyramidal neurons, which were differentiated from embryonic stem (ES) cells. At therapeutic concentrations, VPA had a proapoptotic effect on ES cell-derived NPCs of glutamatergic neurons, but not on their progeny. This effect of VPA most likely occurred through the inhibition of HDACs, because similar phenotypes were observed following treatment with other HDAC inhibitors (HDACis) such as trichostatin A and sodium butyrate. The proapoptotic phenotype was not observed when cells were exposed to a structural analog of VPA, valpromide (VPM), which has the same antiepileptic effect as VPA, but does not inhibit HDACs. Western blotting confirmed that treatment with HDACis, but not VPM, significantly increased the levels of histone H3 acetylation in NPCs. HDACi treatments did not affect the survival of neurons, although the acetylation levels were increased to a limited extent. These results, which are based on a homogeneous culture system, suggest that VPA inhibits HDAC activity and induces the apoptosis of NPCs that are fated to differentiate into glutamatergic neurons. The dose-dependent effects of VPA both on apoptosis and hyperacetylation of histone H3 in NPCs supported this notion. These cell type- and differentiation stage-specific effects of VPA imply that dysfunction of HDACs during pregnancy significantly increase the risk of congenital malformations associated with VPA administration.

Fujiki, R; Sato, A; Fujitani, M; Yamashita, T

2013-01-01

246

A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons.  

PubMed

Valproic acid (VPA) is a branched-chain saturated fatty acid with a long history of clinical use as an antiepileptic drug (AED). VPA is also known to inhibit histone deacetylases (HDACs) and to cause diverse effects on neural progenitor cells (NPCs) and neurons. Although the neuroprotective or neurodestructive effects of VPA have been investigated in heterogeneous cell populations, in this study, we used homogeneous populations of NPCs and glutamatergic cortical pyramidal neurons, which were differentiated from embryonic stem (ES) cells. At therapeutic concentrations, VPA had a proapoptotic effect on ES cell-derived NPCs of glutamatergic neurons, but not on their progeny. This effect of VPA most likely occurred through the inhibition of HDACs, because similar phenotypes were observed following treatment with other HDAC inhibitors (HDACis) such as trichostatin A and sodium butyrate. The proapoptotic phenotype was not observed when cells were exposed to a structural analog of VPA, valpromide (VPM), which has the same antiepileptic effect as VPA, but does not inhibit HDACs. Western blotting confirmed that treatment with HDACis, but not VPM, significantly increased the levels of histone H3 acetylation in NPCs. HDACi treatments did not affect the survival of neurons, although the acetylation levels were increased to a limited extent. These results, which are based on a homogeneous culture system, suggest that VPA inhibits HDAC activity and induces the apoptosis of NPCs that are fated to differentiate into glutamatergic neurons. The dose-dependent effects of VPA both on apoptosis and hyperacetylation of histone H3 in NPCs supported this notion. These cell type- and differentiation stage-specific effects of VPA imply that dysfunction of HDACs during pregnancy significantly increase the risk of congenital malformations associated with VPA administration. PMID:23788034

Fujiki, R; Sato, A; Fujitani, M; Yamashita, T

2013-01-01

247

Regional HLA Differences in Poland and Their Effect on Stem Cell Donor Registry Planning  

PubMed Central

Regional HLA frequency differences are of potential relevance for the optimization of stem cell donor recruitment. We analyzed a very large sample (n?=?123,749) of registered Polish stem cell donors. Donor figures by 1-digit postal code regions ranged from n?=?5,243 (region 9) to n?=?19,661 (region 8). Simulations based on region-specific haplotype frequencies showed that donor recruitment in regions 0, 2, 3 and 4 (mainly located in the south-eastern part of Poland) resulted in an above-average increase of matching probabilities for Polish patients. Regions 1, 7, 8, 9 (mainly located in the northern part of Poland) showed an opposite behavior. However, HLA frequency differences between regions were generally small. A strong indication for regionally focused donor recruitment efforts can, therefore, not be derived from our analyses. Results of haplotype frequency estimations showed sample size effects even for sizes between n?5,000 and n?20,000. This observation deserves further attention as most published haplotype frequency estimations are based on much smaller samples.

Schmidt, Alexander H.; Solloch, Ute V.; Pingel, Julia; Sauter, Jurgen; Bohme, Irina; Cereb, Nezih; Dubicka, Kinga; Schumacher, Stephan; Wachowiak, Jacek; Ehninger, Gerhard

2013-01-01

248

[Embryonic stem cell research].  

PubMed

Research using human embryonic stem cell (hESC) lines has expanded dramatically because of two attractive capacity; self-renewal and differentiation into almost all cell types. For therapeutic purposes, many researchers are trying to establish methods for maintaining pluripotency in defined xeno-free conditions and scalable culture systems. Banking of hESC lines is important for the wide spread of personalized cell therapy and transplantation. We introduced the ongoing clinical trials using hESC-derived cells in patients with subacute spinal cord injury and Stargardt's macular dystrophy. We also discussed opportunities and an example for the use of hESC in drug discovery. Finally, we introduced transgenic hESC as a disease model. PMID:22242306

Kadota, Shin; Aiba, Kazuhiro; Nakatsuji, Norio

2011-12-01

249

Isolation of hematopoietic stem cells and the effect of CD38 expression during the early erythroid progenitor cell development process  

PubMed Central

The aim of this study was to investigate changes in primitive hematopoietic cells through CD38 expression, identify the stage at which erythrocyte differentiation CD38 gains activity and the effects of serum factors on this expression by establishing a hematopoietic stem cell system in the erythroid development process. Using an immunomagnetic labeling and separation technique, CD34+ cells were selected from cord blood. The CD34+ cells were cultured in a 2 mM L-glutamine-enriched medium containing erythropoietin (Epo), penicillin-streptomycin and stem cell factor (SCF), and were incubated in 5% CO2 at 37°C. In erythroid development pathways following CD38 expression, primitive/progenitor human hematopoietic cells obtained from cord blood were assessed through the erythroid development process in a serum-free medium in the presence of proper SCF and Epo. At the end of the 26-day process, using staining with a Megacult-c staining kit, it was determined that progenitor cells nucleate and differentiate into erythroid cell lines of 8–10 ?m. During the course of this process, we analyzed increases over time in NAD glycohydrolase activity rates using the supernatant liquid samples. Results of co-culture experiments in cell culture studies showed that the stimulating effects of CD38 expression originate from specific serum factors. CD38 expression has been shown to occur at hematopoietic cell sources as well as at a number of differentiation levels. In the proliferation process the possible induction of CD38 through specific serum factors leads us to conclude that it may be involved in proliferation with a physiological task or that it may be involved in an event, such as an apoptotic process.

ALBENIZ, IsIL; TURKER-SENER, LEYLA; BAS, AYCAN; KALELIOGLU, IBRAHIM; NURTEN, RUSTEM

2012-01-01

250

Stem cell responses after radiation exposure: A key to the evaluation and prediction of its effects  

SciTech Connect

A biomathematical model of granulocytopoiesis is described and used to analyze the blood granulocyte changes seen in the blood of dogs and humans after continuous and after acute external radiation exposure. This allows to relate the cell change pattern seen to the extent of stem cell damage in the hematopoietic bone marrow distributed as semiautonomous units throughout the skeletal bones. The model is described briefly and consists of 8 cellular and 2 regulatory compartments and is described by 37 differential equations. With the help of this model, it can be shown that the chronic radiation exposure of dogs at a rate of between 0.003 and 0.12 Gy per day results in a system failure with subsequent death of the animal, if the stem cell pool decreases below 2.5% of its normal content. In human beings exposed to a single radiation exposure (as seen in radiation accidents) the simulation of the granulocyte pattern results in the finding that a reduction of the stem pool to 5-10% of normal is compatible with the assumption of its {open_quotes}reversible{close_quotes} damage (to be treated by conventional replacement therapy including cytokines), whereas the reduction of blood granulocytes to levels of less than 200-300 per mm{sup 3} on day 5-6 after exposure indicates that no stem cells remain from which a spontaneous regeneration could occur and hence would require a substitution therapy by stem cell transplantation. The same model was used to correlate the changing granulocyte pattern seen after autologous blood stem cell transfusion in patients treated with supralethal radiochemo conditioning regimen. The results indicate a proportionality of progenitor cells in the transfusate with the calculated stem cell number of the modeling exercise. It is proposed to use the pattern of granulocyte changes in the blood as a principal indicator to predict the outcome of a radiation exposure and to select appropriate therapeutic strategies. 29 refs., 7 figs., 2 tabs.

Fliedner, T.M.; Paul, W.; Tibken, B.; Hofer, E.P. [Univ. of Ulm (Germany)

1996-06-01

251

DEVELOPMENTAL BIOLOGY: Orienting Stem Cells  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Stem cells have the ability to self-renew and to differentiate into a variety of different cell types. However, it is not clear what determines the path taken by any particular stem cell. Discussing recent work with stem cells from the fruit fly testis (Yamashita et al.), Wallenfang and Matunis explain in their Perspective that, at least in the case of these stem cells, the trick is the asymmetric arrangement of the mitotic spindle during cell division. This asymmetric arrangement ensures that as the stem cell divides, one daughter cell remains in the environmental niche of the testis and continues to self-renew, whereas the other daughter cell is edged out of the niche and begins to differentiate.

Matthew R. Wallenfang (University of Pennsylvania;Department of Cell and Developmental Biology); Erika Matunis (The Johns Hopkins Medical Institutions;Department of Cell Biology)

2003-09-12

252

The Effect of Dexamethasone and Triiodothyronine on Terminal Differentiation of Primary Bovine Chondrocytes and Chondrogenically Differentiated Mesenchymal Stem Cells  

PubMed Central

The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal differentiation, they can be used to generate a model of endochondral ossification, but this limitation must be kept in mind when using them in cartilage tissue engineering application.

Randau, Thomas M.; Schildberg, Frank A.; Alini, Mauro; Wimmer, Matthias D.; Haddouti, El-Mustapha; Gravius, Sascha; Ito, Keita; Stoddart, Martin J.

2013-01-01

253

Differential effects on cell motility, embryonic stem cell self-renewal and senescence by diverse Src kinase family inhibitors  

SciTech Connect

The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying molecular mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approximately 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2. -- Highlights: Black-Right-Pointing-Pointer SFK inhibitor SU6656 induces senescence in mouse ES cells. Black-Right-Pointing-Pointer SU6656 inhibits mitosis in a SFK-independent manner via cross-selectivity for Aurora kinases. Black-Right-Pointing-Pointer SFK inhibitor PP2 impairs cell motility in various cell lines, including mouse ES cells. Black-Right-Pointing-Pointer Ensuing impeded motility, PP2 inhibits proliferation of various cells lines except for mouse ES cells. Black-Right-Pointing-Pointer SFK inhibitors PP2 and PD173952 impede spontaneous differentiation in standard mouse ES culture maintenance.

Tamm, Christoffer, E-mail: christoffer.tamm@imbim.uu.se; Galito, Sara Pijuan, E-mail: sara.pijuan@imbim.uu.se; Anneren, Cecilia, E-mail: cecilia.anneren@imbim.uu.se

2012-02-15

254

Microarrayed Materials for Stem Cells  

PubMed Central

Stem cells hold remarkable promise for applications in disease modeling, cancer therapy and regenerative medicine. Despite the significant progress made during the last decade, designing materials to control stem cell fate remains challenging. As an alternative, materials microarray technology has received great attention because it allows for high throughput materials synthesis and screening at a reasonable cost. Here, we discuss recent developments in materials microarray technology and their applications in stem cell engineering. Future opportunities in the field will also be reviewed.

Mei, Ying

2013-01-01

255

Genomic Stability in Stem Cells  

Microsoft Academic Search

\\u000a Accumulated data suggest that the unique function of stem cells to self-renew is under the strong control of a sensor system\\u000a detecting potential threats to genomic integrity. Reactive oxygen species, the most significant mutagens in stem cells, when\\u000a elevated, activate the protective mechanisms blocking self-renewal and at the same time serve as a signal stimulating stem\\u000a cell differentiation. Based on

Irene Riz; Robert G. Hawley

256

Effects of GDNF and LIF on mouse spermatogonial stem cells proliferation in vitro.  

PubMed

Spermatogonial stem cells (SSCs) are the only type of cells that transmit genes to the subsequent generations. The proliferation, cultivation and identification of SSCs in vitro are critical to understanding of male infertility, genetic resources and conservation of endangered species. To investigate the effects of glial cell-derived neurotrophic factor (GDNF) and leukemia inhibitory factor (LIF) on the proliferation of mouse SSCs in vitro, supplement of GDNF and/or LIF were designed to culture SSCs. The testes of 6-8 d mouse were harvested and digested by two-step enzyme digestion method. The SSCs and Sertoli cells were separated by differential plating. Then the SSCs were identified by alkaline phosphatase staining, RT-PCR and indirect immunofluorescence cell analysis. The cellular proliferation capacity was measured by methyl thiazolyl tetrazolium assay. The results showed that addition of 20 and 40 ng/ml of GDNF could strongly promote growth of mouse SSCs (p < 0.05). There was no significant difference between LIF treatment groups and the control group in promoting proliferation of the mouse SSCs (p > 0.05). However, the combination of 20 ng/ml GDNF and 1,000 U/ml LIF could significantly enhance the invitro proliferation of mouse SSCs (p < 0.05), and the OD490 value was 0.696 at day 5 of culture when the density of SSCs was 5-10 × 10(4) cells/ml. PMID:23896701

Wang, Peng; Suo, Li-Juan; Wang, Yan-Feng; Shang, Hua; Li, Guang-Xuan; Hu, Jian-Hong; Li, Qing-Wang

2014-03-01

257

The Effects of Exendine-4 on Insulin Producing Cell Differentiation from Rat Bone Marrow-Derived Mesenchymal Stem Cells  

PubMed Central

Objective The aim of this study was to evaluate the effect of exendin-4 (EX-4) on differentiation of insulin-producing cells (IPCs) from rat bone marrow-derived mesenchymal stem cells (RAT-BM-MSCs). Materials and Methods In this experimental study, RAT-BM-MSCs were cultured and the cells characterized by flow cytometry analysis of cell surface markers. RAT-BM-MSCs were subsequently treated with induction media with or without EX-4. After induction, the presence of IPCs was demonstrated with dithizone (DTZ) staining and gene expression profiles for pancreatic cell differentiation markers (PDX-1, GLUT-2, insulin) were assessed using reverse transcription polymerase chain reaction (RT-PCR). Insulin excreted from differentiated cells was analyzed with radioimmunoassay (RIA). The two-tailed student’s t-test was used for comparison of the obtained values. Results The percentage of DTZ-positive cells significantly increased in EX-4 treated cells (p<0.05). Expression of the islet-associated genes PDX-1, GLUT-2 and insulin genes in EX-4 treated cells was markedly higher than in the cells exposed to differentiation media without EX-4. RIA analysis demonstrated significant release of insulin with the glucose challenge test in EX-4 treated cells compared to EX-4 untreated cells. Conclusion The results of this study have demonstrated that EX-4 can enhance differentiation of IPCs from RAT-BM-MSCs.

Nejad-Dehbashi, Fereshteh; Hashemitabar, Mahmoud; Orazizadeh, Mahmoud; Bahramzadeh, Somaieh; Shahhosseini Pourshoushtary, Elham; Khorsandi, Layasadat

2014-01-01

258

[Effect of SNS-032 on biological activity of hematopoietic stem cells in mice].  

PubMed

This study was aimed to investigate the effect of SNS-032 (C17 H24 N4O2S2) on cell cycle, apoptosis, differentiation and self-renewal of hematopoietic stem cells (HSC) in mice. The self-renewal capability of bone marrow cells was measured by cobblestone forming cell test. The expressions of self-renewal regulation genes, cell cycle-related genes, apoptosis-related genes were measured by real-time PCR. The cell cycle status and apoptosis of HSC and HPC were detected by flow cytometry. The results showed that there was no significant difference of the frequency of HSC between SNS-032 and control group. The expressions of CDK1, CDK2, CDK7 and p27 decreased in HSC (P < 0.05) while the expressions of CDK4, CDK6, p21, p18, p19, Bcl-2, Bax, Puma, p53, Bim1, Sall4 and Notch1 showed no difference between SNS-032 group and control group (P > 0.05). The fraction of viable HSC in each phase of cell cycle remained unchanged after the treatment of SNS-032 (P > 0.05). Furthermore, there was no statistical difference in the apoptotic fractions between control and drug-treated groups (P > 0.05). It is concluded that SNS-032 induce apoptosis of cancer cells. Interestingly, SNS-032 has no significant inhibitory effect on self-renewal and differentiation of normal HSC, as well as no obvious effect inducing apoptosis of normal HSC and HPC. PMID:23815933

Qi, Rui-Zhe; Ji, Qing; Zhang, Li-Yan; Zhang, Yu; Yuan, Wei-Ping; Cheng, Tao; Gao, Ying-Dai; Xu, Jing

2013-06-01

259

DNA damage response in adult stem cells.  

PubMed

This review discusses the processes of DNA-damage-response and DNA-damage repair in stem and progenitor cells of several tissues. The long life-span of stem cells suggests that they may respond differently to DNA damage than their downstream progeny and, indeed, studies have begun to elucidate the unique stem cell response mechanisms to DNA damage. Because the DNA damage responses in stem cells and progenitor cells are distinctly different, stem and progenitor cells should be considered as two different entities from this point of view. Hematopoietic and mammary stem cells display a unique DNA-damage response, which involves active inhibition of apoptosis, entry into the cell-cycle, symmetric division, partial DNA repair and maintenance of self-renewal. Each of these biological events depends on the up-regulation of the cell-cycle inhibitor p21. Moreover, inhibition of apoptosis and symmetric stem cell division are the consequence of the down-regulation of the tumor suppressor p53, as a direct result of p21 up-regulation. A deeper understanding of these processes is required before these findings can be translated into human anti-aging and anti-cancer therapies. One needs to clarify and dissect the pathways that control p21 regulation in normal and cancer stem cells and define (a) how p21 blocks p53 functions in stem cells and (b) how p21 promotes DNA repair in stem cells. Is this effect dependent on p21s ability to inhibit p53? Such molecular knowledge may pave the way to methods for maintaining short-term tissue reconstitution while retaining long-term cellular and genomic integrity. PMID:24484934

Insinga, Alessandra; Cicalese, Angelo; Pelicci, Pier Giuseppe

2014-04-01

260

Role of donor and host cells in muscle-derived stem cell-mediated bone repair: differentiation vs. paracrine effects.  

PubMed

Murine muscle-derived stem cells (MDSCs) have been shown capable of regenerating bone in a critical size calvarial defect model when transduced with BMP 2 or 4; however, the contribution of the donor cells and their interactions with the host cells during the bone healing process have not been fully elucidated. To address this question, C57/BL/6J mice were divided into MDSC/BMP4/GFP, MDSC/GFP, and scaffold groups. After transplanting MDSCs into the critical-size calvarial defects created in normal mice, we found that mice transplanted with BMP4GFP-transduced MDSCs healed the bone defect in 4 wk, while the control groups (MDSC-GFP and scaffold) demonstrated no bone healing. The newly formed trabecular bone displayed similar biomechanical properties as the native bone, and the donor cells directly participated in endochondral bone formation via their differentiation into chondrocytes, osteoblasts, and osteocytes via the BMP4-pSMAD5 and COX-2-PGE2 signaling pathways. In contrast to the scaffold group, the MDSC groups attracted more inflammatory cells initially and incurred faster inflammation resolution, enhanced angiogenesis, and suppressed initial immune responses in the host mice. MDSCs were shown to attract macrophages via the secretion of monocyte chemotactic protein 1 and promote endothelial cell proliferation by secreting multiple growth factors. Our findings indicated that BMP4GFP-transduced MDSCs not only regenerated bone by direct differentiation, but also positively influenced the host cells to coordinate and promote bone tissue repair through paracrine effects.-Gao, X., Usas, A., Proto, J. D., Lu, A., Cummins, J. H., Proctor, A., Chen, C.-W., Huard, J. Role of donor and host cells in muscle-derived stem cell-mediated bone repair: differentiation vs. paracrine effects. PMID:24843069

Gao, Xueqin; Usas, Arvydas; Proto, Jonathan D; Lu, Aiping; Cummins, James H; Proctor, Alexander; Chen, Chien-Wen; Huard, Johnny

2014-08-01

261

Effect of high glucose on extensive culturing of mesenchymal stem cells derived from subcutaneous fat, omentum fat and bone marrow.  

PubMed

Frontline research progresses the applicability of bone marrow and adipose tissue in regenerative medicine, but fails to account for the functional improvement of the diseased. The justification for the failure in terms of stem cell survival, proliferation and regeneration is unclear. However, hyperglycemia rising during pathological conditions might be one such stumbling block. The prevailing literature accounts for both detrimental and beneficial effect of high glucose on mesenchymal stem cells (MSCs) leading to perplexity. Thus, this study focuses on the effect of high glucose on mesenchymal stem cells derived from subcutaneous fat, omentum fat and bone marrow in extensive cultures. We provide evidence for the retention of MSC characteristics of all sources with regards to surface marker profiling, proliferation, differentiation and karyotyping when cultured extensively under DMEM-HG containing glucose concentration of 25 mmol.l(-1) . Thus, it can be concluded that hyperglycemia in vivo (11 mmol.l(-1) ) might not be a barrier for the ineffective functional improvement of transplanted stem cells. Furthermore, we elucidated subcutaneous and omentum fat as better sources of MSCs when compared with bone marrow, thereby making these sources optimal for therapies during hyperglycemic conditions. However, further research is needed to clear the path for efficient stem cell transplantation. PMID:22729714

Dhanasekaran, M; Indumathi, S; Rajkumar, J S; Sudarsanam, D

2013-01-01

262

Stem cells in neurology - current perspectives.  

PubMed

Central nervous system (CNS) restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective : The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method : Literature review of animal and human clinical experimental trials, using the following key words: "stem cell", "neurogenesis", "Parkinson", "Huntington", "amyotrophic lateral sclerosis", "traumatic brain injury", "spinal cord injury", "ischemic stroke", and "demyelinating diseases". Conclusion : Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS. PMID:24964114

Batista, Chary Ely Marquez; Mariano, Eric Domingos; Marie, Suely Kazue Nagahashi; Teixeira, Manoel Jacobsen; Morgalla, Matthias; Tatagiba, Marcos; Li, Jun; Lepski, Guilherme

2014-06-01

263

Mechanotransduction: Tuning Stem Cells Fate  

PubMed Central

It is a general concern that the success of regenerative medicine-based applications is based on the ability to recapitulate the molecular events that allow stem cells to repair the damaged tissue/organ. To this end biomaterials are designed to display properties that, in a precise and physiological-like fashion, could drive stem cell fate both in vitro and in vivo. The rationale is that stem cells are highly sensitive to forces and that they may convert mechanical stimuli into a chemical response. In this review, we describe novelties on stem cells and biomaterials interactions with more focus on the implication of the mechanical stimulation named mechanotransduction.

D'Angelo, Francesco; Tiribuzi, Roberto; Armentano, Ilaria; Kenny, Jose Maria; Martino, Sabata; Orlacchio, Aldo

2011-01-01

264

Stem Cell Glycolipids  

Microsoft Academic Search

Glycolipids are compounds containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety.\\u000a Because of their expression patterns and the intracellular localization patterns, glycolipids, including stage-specific embryonic\\u000a antigens (SSEA-3, SSEA-4, and possibly SSEA-1) and gangliosides (e.g., GD3, GD2, and A2B5 antigens), have been used as marker\\u000a molecules of stem cells. In this review, I will

Makoto Yanagisawa

265

Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell associations and spermatogonial stem cells in mice.  

PubMed

Recent evidence has linked human phthalate exposure to abnormal reproductive and hormonal effects. Phthalates are plasticizers that confer flexibility and transparency to plastics, but they readily contaminate the body and the environment. In this study, timed pregnant CD1 outbred mice were treated with di-(2-ethylhexyl) phthalate (DEHP) from Embryonic Day 7 (E7) to E14. The subsequent generation (F1) offspring were then bred to produce the F2, F3, and F4 offspring, without any further DEHP treatment. This exposure scheme disrupted testicular germ cell association and decreased sperm count and motility in F1 to F4 offspring. By spermatogonial transplantation techniques, the exposure scheme also disrupted spermatogonial stem cell (SSC) function of F3 offspring. The W/W(V) recipient testes transplanted with F3 offspring germ cells from the DEHP-treated group had a dramatically lower percentage of donor germ cell-derived spermatogenic recovery in seminiferous tubules when compared to the recipient testes transplanted with CD1 control germ cells. Further characterization showed that the major block of donor germ cell-derived spermatogenesis was before the appearance of undifferentiated spermatogonia. Interestingly, the testes transplanted with the F3 offspring germ cells from the DEHP-treated group, when regenerated, replicated testis morphology similar to that observed in the testes from the F1 to F3 offspring of the DEHP-treated group, suggesting that the germ cell disorganization phenotype originates from the stem cells of F3 offspring. In conclusion, embryonic exposure to DEHP was found to disrupt testicular germ cell organization and SSC function in a transgenerational manner. PMID:23536373

Doyle, Timothy J; Bowman, Jennifer L; Windell, Veronica L; McLean, Derek J; Kim, Kwan Hee

2013-05-01

266

Transgenerational Effects of Di-(2-ethylhexyl) Phthalate on Testicular Germ Cell Associations and Spermatogonial Stem Cells in Mice1  

PubMed Central

ABSTRACT Recent evidence has linked human phthalate exposure to abnormal reproductive and hormonal effects. Phthalates are plasticizers that confer flexibility and transparency to plastics, but they readily contaminate the body and the environment. In this study, timed pregnant CD1 outbred mice were treated with di-(2-ethylhexyl) phthalate (DEHP) from Embryonic Day 7 (E7) to E14. The subsequent generation (F1) offspring were then bred to produce the F2, F3, and F4 offspring, without any further DEHP treatment. This exposure scheme disrupted testicular germ cell association and decreased sperm count and motility in F1 to F4 offspring. By spermatogonial transplantation techniques, the exposure scheme also disrupted spermatogonial stem cell (SSC) function of F3 offspring. The W/WV recipient testes transplanted with F3 offspring germ cells from the DEHP-treated group had a dramatically lower percentage of donor germ cell-derived spermatogenic recovery in seminiferous tubules when compared to the recipient testes transplanted with CD1 control germ cells. Further characterization showed that the major block of donor germ cell-derived spermatogenesis was before the appearance of undifferentiated spermatogonia. Interestingly, the testes transplanted with the F3 offspring germ cells from the DEHP-treated group, when regenerated, replicated testis morphology similar to that observed in the testes from the F1 to F3 offspring of the DEHP-treated group, suggesting that the germ cell disorganization phenotype originates from the stem cells of F3 offspring. In conclusion, embryonic exposure to DEHP was found to disrupt testicular germ cell organization and SSC function in a transgenerational manner.

Doyle, Timothy J.; Bowman, Jennifer L.; Windell, Veronica L.; McLean, Derek J.; Kim, Kwan Hee

2013-01-01

267

Stem cells in gastroenterology and hepatology  

Microsoft Academic Search

Cellular and tissue regeneration in the gastrointestinal tract and liver depends on stem cells with properties of longevity, self-renewal and multipotency. Progress in stem cell research and the identification of potential esophageal, gastric, intestinal, colonic, hepatic and pancreatic stem cells provides hope for the use of stem cells in regenerative medicine and treatments for disease. Embryonic stem cells and induced

Michael Quante; Timothy C. Wang

2009-01-01

268

Evaluating the effects of lenalidomide induction therapy on peripheral stem cells collection in patients undergoing autologous stem cell transplant for multiple myeloma  

PubMed Central

Introduction Lenalidomide (LEN) is a relatively new and very effective therapy for multiple myeloma (MM). Prior LEN therapy is associated with an increased risk of peripheral blood stem cell collection (PBSC) failure, particularly with filgrastim (G-CSF) alone. We performed a retrospective chart review of 319 consecutive MM patients who underwent apheresis to collect PBSCs for the first autologous stem cell transplant (ASCT). Results The median number of PBSCs collected in the LEN (+) group was significantly less than the LEN (?) group (6.34 vs. 7.52×106 CD34+ cells/kg; p=0.0004). In addition, the median number of apheresis sessions required for adequate PBSCs collection were significantly more in the LEN (+) group as compared to LEN (?) group (2 vs. 1 sessions; p=0.002). In the LEN (+) group, there was a negative correlation between PBSCs collected and prior number of cycles of LEN (p=0.0001). Rate of PBSC collection failure was 9 % in the LEN (+) group and 5 % in the LEN (?) group (p=0.16). Only six patients who failed PBSC collection with G-CSF were able to collect adequate PBSCs with G-CSF + plerixafor. LEN exposure had no effect on neutrophil or platelet recovery post-ASCT. Conclusions Up to four cycles of LEN exposure have minimal negative impact on PBSC collection. Despite prolong exposure of LEN, PBSC collection was adequate for two ASCTs in the majority of patients and post-ASCT engraftment was not longer than expected; however, clinical relevance (complication rate, quality of life, cost) of prolonged LEN exposure on both PBSC and ASCT, should be evaluated in prospective clinical trials.

Bhutani, Divaya; Zonder, Jeffrey; Valent, Jason; Tageja, Nishant; Ayash, Lois; Deol, Abhinav; Al-Kadhimi, Zaid; Abrams, Judith; Lum, Lawrence; Ratanatharathorn, Voravit; Uberti, Joseph

2013-01-01

269

Cancer stem cell detection and isolation.  

PubMed

Only 10 % of cancer-related deaths result from primary tumors; most are caused by metastatic tumors. It is believed that the metastatic power of tumor cells is attributed to features of a stem cell-like subpopulation of tumor cells known as cancer stem cells (CSCs). Cancer stem cells are resistant to chemotherapeutic treatments and can induce dormancy in tumor cells for long periods. Detection, isolation, and characterization of CSCs in solid tumors are hallmarks of cancer-targeted therapies in recent years. There are inevitable similarities between normal and cancer stem cells; therefore, finding specific methods or markers to differentiate them is critical to cancer therapies. Considering CSCs involvement in tumor relapse and chemotherapeutic resistance, identification of such cells in tumors is imperative for effective targeted therapy. The present review introduces practical and specific protocols used to isolate CSCs from solid tumors from colon, esophagus, liver, breast, brain, and cervix. PMID:25064729

Moghbeli, Meysam; Moghbeli, Faezeh; Forghanifard, Mohammad Mahdi; Abbaszadegan, Mohammad Reza

2014-09-01

270

Effect of vincristine or bleomycin on radiation-induced cell killing of mice spermatogonial stem cells: The importance of sequence and time interval  

SciTech Connect

The effect of single doses of vincristine (VCR) or bleomycin (BLM) on mice spermatogonia was investigated, and the influence of either of these drugs on the radiation response of murine spermatogonial stem cells was examined. When assessed by flow cytometry, VCR (1.0 mg/kg) or BLM (100 mg/kg) reduced the survival in the differentiated spermatogonia to 4% and 37% of controls, respectively (p less than 0.05). VCR reduced the stem cells to 79% of controls (p less than 0.05), whereas BLM had no apparent effect on the stem cells (p greater than 0.05). Drugs were administered intraperitoneally up to 28 days before or after local irradiation with 9 Gy. VCR produced significant enhancement of radiation-induced damage to spermatogonial stem cells, which was most prominent when administered 6 or 12 hr after irradiation. BLM administered before irradiation or 1 hr after radiotherapy produced significant enhancement.

Hansen, P.V.; Sorensen, D. (Danish Cancer Society, Aarhus (Denmark))

1991-02-01

271

Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells  

PubMed Central

Umbilical cord blood (CB) has become, since its first successful use more than two decades ago, an increasingly important source of blood stem cells. In this light, an overview of current usage of CB in the field of unrelated hematopoietic blood stem cell transplantation (HSCT) is given. The three main sources of hematopoietic stem cells: bone marrow (BM), peripheral blood stem cells (PBSC), and cord blood (CB) are compared as regards their current quantitative usage in HSCT. A cost analysis of the named three hematopoietic blood stem cell (HSC) sources, taking into account various factors, is undertaken. The health economical comparison shows significant differences between CB on the one side, and BM and PBSC on the other. The consequences for the public health side and propositions for a possible health care policy, especially regarding future resource allocation towards the different choices for HSCT products, are discussed. An outlook on the possible future usage of BM, PBSC, and CB and its implications on health systems, donor registries, and CB banks is given.

Bart, Thomas

2010-01-01

272

Effects of substrate stiffness on adipogenic and osteogenic differentiation of human mesenchymal stem cells.  

PubMed

Substrate mechanical properties, in addition to biochemical signals, have been shown to modulate cell phenotype. In this study, we inspected the effects of substrate stiffness on human mesenchymal stem cells (hMSCs) derived from adult human bone marrow differentiation into adipogenic and osteogenic cells. A chemically modified extracellular matrix derived and highly biocompatible hydrogel, based on thiol functionalized hyaluronic acid (HA-SH) and thiol functionalized recombinant human gelatin (Gtn-SH), which can be crosslinked by poly (ethylene glycol) tetra-acrylate (PEGTA), was used as a model system. The stiffness of the hydrogel was controlled by adjusting the crosslinking density. Human bone marrow MSCs were cultured on the hydrogels with different stiffness under adipogenic and osteogenic conditions. Oil Red O staining and F-actin staining were applied to assess the change of cell morphologies under adipogenic and osteogenic differentiation, respectively. Gene expression of cells was determined with reverse transcription polymerase chain reaction (RT-PCR) as a function of hydrogel stiffness. Results support the hypothesis that adipogenic and osteogenic differentiation of hMSCs are inclined to occur on substrate with stiffness similar to their in vivo microenvironments. PMID:24857499

Zhao, Wen; Li, Xiaowei; Liu, Xiaoyan; Zhang, Ning; Wen, Xuejun

2014-07-01

273

The effect of mesenchymal stem cell shape on the maintenance of multipotency.  

PubMed

Human mesenchymal stem cells (MSCs) have broad therapeutic potential due to their ability to differentiate into multiple cell types. However, when cultured ex vivo MSCs will spontaneously differentiate and have been shown to lose multipotency after prolonged passaging. Cell culture conditions that promote maintenance of multipotency during in vitro expansion are a critical need to fully realize the therapeutic potential of MSCs. Here we show that by confining MSCs to small islands, we can restrict inappropriate lineage specification and enhance the expression of mesenchymal stem cell markers Stro-1 and Endoglin. Even when released from the islands and reseeded, cells previously cultured in patterns maintain higher expression of MSC markers compared to cells cultured on plastic, while maintaining their ability to differentiate into adipocytes and osteoblasts. Exposure of non-patterned cells to inhibitors of myosin and Rho-associated protein kinase (ROCK) leads to increased expression of stem cell markers. Our findings suggest that maintenance of MSC "stemness" requires a low state of actomyosin contractility. This work will prove useful in the development of culture conditions for the maintenance of multipotent MSCs in vitro and for the design of niche-mimetic biomaterials. PMID:23473964

Zhang, Douglas; Kilian, Kristopher A

2013-05-01

274

Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate cancer stem cells  

PubMed Central

Improved treatments for prostate cancer are in great need to overcome lethal recurrence and metastasis. Targeting the tumorigenic cancer stem cells (CSCs) with self-renewal and differentiation capacity appears to be a promising strategy. Blockade of the hedgehog (Hh) signaling pathway, an important pathway involved in stem cell self-renewal, by cyclopamine leads to long-term prostate cancer regression without recurrence, strongly suggesting the connection between Hh pathway and prostate CSCs. Here we designed a HPMA (N-(2-hydroxypropyl)methacrylamide)-based cyclopamine delivery system as a CSC-selective macromolecular therapeutics with improved drug solubility and decreased systemic toxicity. To this end, HPMA and N-methacryloylglycylphenylalanylleucylglycyl thiazolidine-2-thione were copolymerized using the RAFT (reversible addition-fragmentation chain transfer) process, followed by polymer-analogous attachment of cyclopamine. The selectivity of the conjugate toward CSCs was evaluated on RC-92a/hTERT cells, the human prostate cancer epithelial cells with human telomerase reverse transcriptase transduction. The use of RC-92a/hTERT cells as an in vitro CSC model was validated by stem cell marker expression and prostasphere culture. The bioactivity of cyclopamine was retained after conjugation to the polymer. Furthermore, HPMA polymer-conjugated cyclopamine showed anti-CSC efficacy on RC-92a/hTERT cells as evaluated by decreased stem cell marker expression and CSC viability.

Zhou, Yan; Yang, Jiyuan; Kopecek, Jindrich

2011-01-01

275

95. Effective Genetic Engineering of Human Embryonic Stem Cells Using the Sleeping Beauty Transposon System  

Microsoft Academic Search

Human embryonic stem (ES) cells hold great promise for the study of human development and the generation of new therapeutic approaches to tissue regeneration and their genetic modification will play a key role in this development. While viral vectors have been readily used for gene transfer into human ES cells, only limited success has been achieved using non-viral vectors for

Andrew Wilber; Jonathan L. Linehan; Xinghui Tian; R. Scott McIvor; Dan S. Kaufman

2006-01-01

276

Effects of nicotine on proliferation and survival in human umbilical cord mesenchymal stem cells.  

PubMed

Cigarette smoking is known to have negative effects on tissue repair and healing. The aim of this study is to investigate the effects of nicotine in human umbilical cord mesenchymal stem cells (MSCs). After nicotine treatment, MSCs became pyknotic, vacuoles appeared in the cytoplasm and nucleus, and the nuclear boundary became fuzzy as observed using atomic force microscopy. Cell proliferation was inhibited in a dose-dependent manner (P < 0.05 for all concentrations). The proportion of apoptotic MSCs was significantly increased in a dose-dependent manner. The mitochondrial membrane potential was significantly decreased (P < 0.05). Nicotine-treated MSCs had a significantly higher G0/G1 ratio (P < 0.05). Peptide mass fingerprinting identified 27 proteins that were differentially expressed between MSCs with and without nicotine treatment. These nicotine exerted toxic effects on MSCs are likely related, at least in part, to the altered expression of multiple proteins that are essential to the health and proliferation of these cells. PMID:24488958

Zeng, Hui-Lan; Qin, Yong-Liang; Chen, Hui-Zhong; Bu, Qian-Qian; Li, Yang; Zhong, Qi; Han, Xin-Ai; Chen, Jie; Yu, Pan-Xi; Liu, Ge-Xiu

2014-04-01

277

Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces in vitro: a potential beneficial therapeutic effect.  

PubMed

Aim: Injury of tendons contained within a synovial environment, such as joint, bursa or tendon sheath, frequently fails to heal and releases matrix proteins into the synovial fluid, driving inflammation. This study investigated the effectiveness of cells to seal tendon surfaces and provoke matrix synthesis as a possible effective injectable therapy. Materials & methods: Equine flexor tendon explants were cultured overnight in suspensions of bone marrow and synovium-derived mesenchymal stems cells and, as controls, two sources of fibroblasts, derived from tendon and skin, which adhered to the explants. Release of the most abundant tendon extracellular matrix proteins into the media was assayed, along with specific matrix proteins synthesis by real-time PCR. Results: Release of extracellular matrix proteins was influenced by the coating cell type. Fibroblasts from skin and tendon appeared less capable of preventing the release of matrix proteins than mesenchymal stems cells. Conclusion: The source of cell is an important consideration for cell therapy. PMID:24935042

Garvican, Elaine R; Dudhia, Jayesh; Alves, Ana-Liz; Clements, Lucy E; Plessis, Francois Du; Smith, Roger Kw

2014-05-01

278

Cellular and molecular effects of high-LET radiation on human neural stem cells and neurons  

NASA Astrophysics Data System (ADS)

Because successful operations in space depend in part on the performance capabilities of astronauts, radiation-induced neurological damage could jeopardize the successful completion of mission requirements, as well as have long-term consequences on the health of astronauts. As such, understanding the nature of this risk may be vital to the effective performance of astronauts during future missions in space. This paper describes the neural cell responses to conventional and charged particles radiation in cell culture systems. One of the goals is to characterize radiation-induced neural cell damage pathways; especially those related to apoptosis induction and its modification by pharmacological manipulation. Our laboratory utilizes the method of flow cytometry to measure the induction of apoptosis and necrosis in cells. Neural stem cells (NT2) were exposed to the different ions; we measured a dose-dependent induction of apoptosis. NT2 cells were exposed to graded doses of 1 and 5 GeV/n Fe, 0.29 GeV/n C, 1 GeV/n Ti, and 0.6 GeV/n Si ions and samples were taken at 48 hours after exposure. The percentage of apoptotic cells in culture was measured by FITC-Annexin V by flow cytometry. Similar data obtained from NT2 cells exposed to 255 MeV/n protons and 137Cs are included for comparison. Preliminary RBE calculations demonstrated that iron ions are more effective in inducing apoptosis. Exposure of cells to ionizing radiation produces changes in the expression of many genes as cells react to this insult. At present, the identities of the molecular changes that occur in response to HZE radiation remain largely unknown. In an effort to reveal this information, we screened an array (Superarray) of p53-related genes with RNA purified from NT2 cells mock irradiated or exposed to 50 cGy of 1 GeV/n iron ions. Preliminary results indicated that the expression of numerous critical genes was altered 3 hours after HZE radiation exposure. By performing Western blot analysis on NT2 cells exposed to 5 GeV/n iron ions, we demonstrated a time and dose dependent increase in p53 protein levels. This induction occurred as early as 6 hours post-irradiation, and was detectable with a dose as low as 10 cGy. Meanwhile, the levels of the structural protein actin did not change in these cell samples, assuring accurate protein quantization and equal loading from sample to sample. We have also shown a time and dose dependent increase in p53 protein levels in terminally differentiated human neuronal (hNT) cells exposed to 1 GeV/n iron ions. Using a more detailed protocol of early harvesting times, we determined that p53 accumulated in these neuronal cells within 8 hours after irradiation. Our laboratory's demonstration that HZE radiation exposure results in a dose dependent induction of p53 protein, concomitant with our finding of a dose dependent induction of apoptosis in the neural stem (NT2) cells, strongly implies that p53 plays a major role in this HZE radiation-induced apoptosis response.

Vazquez, M.; Guida, P.; Green, L.; Chang, P.; Otto, S.

279

The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes  

PubMed Central

The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM) on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC—in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE)—has great merits for skin regeneration. In this study, human primary keratinocytes (HKs), which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 ?g/mL) than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05) notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 ?g/mL). AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-?3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration.

Moon, Kyoung Mi; Park, Ye-Hyoung; Lee, Jae Seol; Chae, Yong-Byung; Kim, Moon-Moo; Kim, Dong-Soo; Kim, Byung-Woo; Nam, Soo-Wan; Lee, Jong-Hwan

2012-01-01

280

Induction of Cancerous Stem Cells during Embryonic Stem Cell Differentiation*  

PubMed Central

Stem cell maintenance depends on their surrounding microenvironment, and aberrancies in the environment have been associated with tumorigenesis. However, it remains to be elucidated whether an environmental aberrancy can act as a carcinogenic stress for cellular transformation of differentiating stem cells into cancer stem cells. Here, utilizing mouse embryonic stem cells as a model, it was illustrated that environmental aberrancy during differentiation leads to the emergence of pluripotent cells showing cancerous characteristics. Analogous to precancerous stages, DNA lesions were spontaneously accumulated during embryonic stem cell differentiation under aberrational environments, which activates barrier responses such as senescence and apoptosis. However, overwhelming such barrier responses, piled-up spheres were subsequently induced from the previously senescent cells. The sphere cells exhibit aneuploidy and dysfunction of the Arf-p53 module as well as enhanced tumorigenicity and a strong self-renewal capacity, suggesting development of cancerous stem cells. Our current study suggests that stem cells differentiating in an aberrational environment are at risk of cellular transformation into malignant counterparts.

Fujimori, Hiroaki; Shikanai, Mima; Teraoka, Hirobumi; Masutani, Mitsuko; Yoshioka, Ken-ichi

2012-01-01

281

Histolgical AND Immunohistochemical Study on the Effect of Stem Cell Therapy on Bleomycin Induced Pulmonary Fibrosis in Albino Rat  

PubMed Central

Aim of work: To demonstrate the bleomycin induced histological changes in the lung and the possible protective and/or therapeutic effect of stem cell therapy. Materials and methods: Study was carried out on 36 adult male albino rats, classified into 4 groups: group I (control), group II (bleomycin treated group), group III (early stem cell treated group: immediately after bleomycin), group IV (late stem cell treated group: 7 days after bleomycin). Sections were taken at the 14th day of experiment. stained with Hematoxylin and Eosin, Masson’s trichrome, immunohistochemichal stains for ?-SMA & PCNA. Sections were examined by light & immunofluroscent microscopy. Area percent of collagen fibers, area percent & optical density of ?-SMA immunopositive cells were measured as well as the number of H&E and PCNA stained pneumocytes type II was counted. Results: Group II showed, thickening of septa, extravasation of blood, dividing pneumocytes type II cells with acinar formation, cellular infiltration, fibroblast cells, almost complete loss of normal lung architecture in certain fields, consolidation and replacement of the lung tissue with fibrous tissue in other fields. Restoring of lung tissue with significant decrease in mean area % of collagen fibers, ?-SMA immunopositive cells were detected in group III. Conclusions: Early treatment with bone marrow derived mesenchymal stem cells (BMSCs) immediately after bleomycin administration showed a significant reduction in fibrotic changes, however the late treatment with BMSCs (7 days) after bleomycin administration showed non significant results.

Sabry, Marwa Mohammed; Elkalawy, Seham Abd-Elhamed; Abo-Elnour, Rahma Kamal El-din; Abd-El-Maksod, Dalia Fathy

2014-01-01

282

Monoclonal antibody targeting of IL-3 receptor ? with CSL362 effectively depletes CML progenitor and stem cells.  

PubMed

Despite the remarkable efficacy of tyrosine kinase inhibitors (TKIs) in eliminating differentiated chronic myeloid leukemia (CML) cells, recent evidence suggests that leukemic stem and progenitor cells (LSPCs) persist long term, which may be partly attributable to cytokine-mediated resistance. We evaluated the expression of the interleukin 3 (IL-3) receptor ? subunit (CD123), an established marker of acute myeloid leukemia stem cells, on CML LSPCs and the potential of targeting those cells with the humanized anti-CD123 monoclonal antibody CSL362. Compared with normal donors, CD123 expression was higher in CD34(+)/CD38(-) cells of both chronic phase and blast crisis CML patients, with levels increasing upon disease progression. CSL362 effectively targeted CML LSPCs by selective antibody-dependent cell-mediated cytotoxicity (ADCC)-facilitated lysis of CD123(+) cells and reduced leukemic engraftment in mice. Importantly, not only were healthy donor allogeneic natural killer (NK) cells able to mount an effective CSL362-mediated ADCC response, but so were CML patients' autologous NK cells. In addition, CSL362 also neutralized IL-3-mediated rescue of TKI-induced cell death. Notably, combination of TKI- and CSL362-induced ADCC caused even greater reduction of CML progenitors and further augmented their preferential elimination over normal hematopoietic stem and progenitor cells. Thus, our data support the further evaluation of CSL362 therapy in CML. PMID:24363400

Nievergall, Eva; Ramshaw, Hayley S; Yong, Agnes S M; Biondo, Mark; Busfield, Samantha J; Vairo, Gino; Lopez, Angel F; Hughes, Timothy P; White, Deborah L; Hiwase, Devendra K

2014-02-20

283

Preconditioning Strategy in Stem Cell Transplantation Therapy  

PubMed Central

Stem cell transplantation therapy has emerged as a promising regenerative medicine for ischemic stroke and other neurodegenerative disorders. However, many issues and problems remain to be resolved before successful clinical applications of the cell-based therapy. To this end, some recent investigations have sought to benefit from well-known mechanisms of ischemic/hypoxic preconditioning. Ischemic/hypoxic preconditioning activates endogenous defense mechanisms that show marked protective effects against multiple insults found in ischemic stroke and other acute attacks. As in many other cell types, a sub-lethal hypoxic exposure significantly increases the tolerance and regenerative properties of stem cells and progenitor cells. So far, a variety of preconditioning triggers have been tested on different stem cells and progenitor cells. Preconditioned stem cells and progenitors generally show much better cell survival, increased neuronal differentiation, enhanced paracrine effects leading to increased trophic support, and improved homing to the lesion site. Transplantation of preconditioned cells helps to suppress inflammatory factors and immune responses, and promote functional recovery. Although the preconditioning strategy in stem cell therapy is still an emerging research area, accumulating information from reports over the last few years already indicates it as an attractive, if not essential, prerequisite for transplanted cells. It is expected that stem cell preconditioning and its clinical applications will attract more attention in both the basic research field of preconditioning as well as in the field of stem cell translational research. This review summarizes the most important findings in this active research area, covering the preconditioning triggers, potential mechanisms, mediators, and functional benefits for stem cell transplant therapy.

Yu, Shan Ping; Wei, Zheng; Wei, Ling

2013-01-01

284

Effect of Human Parathyroid Hormone on Hematopoietic Progenitor Cells in NOD/SCID Mice Co-Transplanted with Human Cord Blood Mononuclear Cells and Mesenchymal Stem Cells  

PubMed Central

Purpose We evaluated the effect of human parathyroid hormone (hPTH) on the engraftment and/or in vivo expansion of hematopoietic stem cells in an umbilical cord blood (UCB)-xenotransplantation model. In addition, we assessed its effect on the expression of cell adhesion molecules. Materials and Methods Female NOD/SCID mice received sublethal total body irradiation with a single dose of 250 cGy. Eighteen to 24 hours after irradiation, 1×107 human UCB-derived mononuclear cells (MNCs) and 5×106 human UCB-derived mesenchymal stem cells (MSCs) were infused via the tail vein. Mice were randomly divided into three groups: Group 1 mice received MNCs only, Group 2 received MNCs only and were then treated with hPTH, Group 3 mice received MNCs and MSCs, and were treated with hPTH. Results Engraftment was achieved in all the mice. Bone marrow cellularity was approximately 20% in Group 1, but 70-80% in the hPTH treated groups. Transplantation of MNCs together with MSCs had no additional effect on bone marrow cellularity. However, the proportion of human CD13 and CD33 myeloid progenitor cells was higher in Group 3, while the proportion of human CD34 did not differ significantly between the three groups. The proportion of CXCR4 cells in Group 3 was larger than in Groups 1 and 2 but without statistical significance. Conclusion We have demonstrated a positive effect of hPTH on stem cell proliferation and a possible synergistic effect of MSCs and hPTH on the proportion of human hematopoietic progenitor cells, in a xenotransplantation model. Clinical trials of the use of hPTH after stem cell transplantation should be considered.

Lim, Yeon-Jung; Hwang, Kyoujung; Kim, Miyeon; Cho, Youl-Hee; Lee, Jong-Hwa

2013-01-01

285

Inducible effects of icariin, icaritin, and desmethylicaritin on directional differentiation of embryonic stem cells into cardiomyocytes in vitro  

Microsoft Academic Search

Aim:To investigate the possible inducible effects of icariin, icaritin, and desmethylicaritin on the directional differentiation of embryonic stem (ES) cells into cardiomyocytes in vitro.Methods:ES cells were cultivated as embryoid bodies (EBs) in hanging drops with icariin, icaritin, or desmethylicaritin. ES cells treated with retinoic acid and with solvent were used as positive and negative controls, respectively. The cardiomyocytes derived from

Dan-yan Zhu; Yi-jia Lou

2005-01-01

286

Adenosine potentiates the therapeutic effects of neural stem cells expressing cytosine deaminase against metastatic brain tumors.  

PubMed

Tumor-tropic properties of neural stem cells (NSCs) provide a novel approach with which to deliver targeting therapeutic genes to brain tumors. Previously, we developed a therapeutic strategy against metastatic brain tumors using a human NSC line (F3) expressing cytosine deaminase (F3.CD). F3.CD converts systemically administered 5-fluorocytosine (5-FC), a blood-brain barrier permeable nontoxic prodrug, into the anticancer agent 5-fluorouracil (5-FU). In this study, we potentiated a therapeutic strategy of treatment with nucleosides in order to chemically facilitate the endogenous conversion of 5-FU to its toxic metabolite 5-FU ribonucleoside (5-FUR). In vitro, 5-FUR showed superior cytotoxic activity against MDA-MB-435 cancer cells when compared to 5-FU. Although adenosine had little cytotoxic activity, the addition of adenosine significantly potentiated the in vitro cytotoxicity of 5-FU. When MDA-MB?435 cells were co-cultured with F3.CD cells, F3.CD cells and 5-FC inhibited the growth of MDA-MB-435 cells more significantly in the presence of adenosine. Facilitated 5-FUR production by F3.CD was confirmed by an HPLC analysis of the conditioned media derived from F3.CD cells treated with 5-FC and adenosine. In vivo systemic adenosine treatment also significantly potentiated the therapeutic effects of F3.CD cells and 5-FC in an MDA-MB-435 metastatic brain tumor model. Simple adenosine addition improved the antitumor activity of the NSCs carrying the therapeutic gene. Our results demonstrated an increased therapeutic potential, and thereby, clinical applicability of NSC-based gene therapy. PMID:23828015

Kang, Wonyoung; Seol, Ho Jun; Seong, Dong-Ho; Kim, Jandi; Kim, Yonghyun; Kim, Seung U; Nam, Do-Hyun; Joo, Kyeung Min

2013-09-01

287

Effects of external radiation in a co-culture model of endothelial cells and adipose-derived stem cells  

PubMed Central

Background The inflammatory response clinically observed after radiation has been described to correlate with elevated expression of cytokines and adhesion molecules by endothelial cells. Therapeutic compensation for this microvascular compromise could be an important approach in the treatment of irradiated wounds. Clinical reports describe the potential of adipose-derived stem cells to enhance wound healing, but the underlying cellular mechanisms remain largely unclear. Methods Human dermal microvascular endothelial cells (HDMEC) and human adipose-derived stem cells (ASC) were cultured in a co-culture setting and irradiated with sequential doses of 2 to 12 Gy. Cell count was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the supernatants using enzyme-linked immunosorbent assay (ELISA). Irradiated HDMEC and ASC as well as non-irradiated co-cultures, HDMEC or ASC respectively were used as controls. Results Cell count was significantly reduced in irradiated co-cultures of HDMEC and ASC compared to non-irradiated controls. Levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of the co-cultures were significantly less affected by external radiation in comparison to HDMEC. Conclusion The increased expression of cytokines and adhesion molecules by HDMEC after external radiation is mitigated in the co-culture setting with ASC. These in vitro changes seem to support the clinical observation that ASC may have a stabilizing effect when injected into irradiated wounds.

2013-01-01

288

Bioprinting for stem cell research  

PubMed Central

Recently, there has been a growing interest to apply bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized proteins can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cell of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics.

Tasoglu, Savas; Demirci, Utkan

2012-01-01

289

Doxorubicin has in vivo toxicological effects on ex vivo cultured mesenchymal stem cells.  

PubMed

Doxorubicin (dox) is an effective chemotherapeutic agent that leads to cardiotoxicity. An alternative treatment for dox-cardiotoxicity is autologous mesenchymal stem cells (MSCs) transplantation. It remains unclear if dox has deleterious effects on MSCs from subjects under chemotherapy, therefore this study aimed to evaluate dox in vivo toxicological effects on ex vivo cultured MSCs, inferring whether autologous transplantation may be an alternative treatment in patients who are exposed to the drug. Wistar rats received either dox or saline. Following treatments, animals were sacrificed and bone marrow MSCs were isolated, characterized for cell surface markers and assessed according to their viability, alkaline phosphatase production, and proliferation kinetics. Moreover, MSCs were primed to cardiac differentiation and troponin T and connexin 43 expressions were evaluated. Compared to control, undifferentiated MSCs from dox group kept the pattern for surface marker and had similar viability results. In contrast, they showed lower alkaline phosphatase production, proliferation rate, and connexin 43 expression. Primed MSCs from dox group showed lower troponin T levels. It was demonstrated a toxic effect of dox in host MSCs. This result renders the possibility of autologous MSCs transplantation to treat dox-cardiotoxicity, which could be a non-suitable option for subjects receiving such antineoplastic agent. PMID:24291741

Oliveira, Maira Souza; Carvalho, Juliana Lott; Campos, Ana Carolina De Angelis; Gomes, Dawidson Assis; de Goes, Alfredo Miranda; Melo, Marília Martins

2014-01-30

290

EpCAM is a putative stem marker in retinoblastoma and an effective target for T-cell-mediated immunotherapy  

PubMed Central

Purpose The molecular markers cluster of differentiation (CD)24, CD44, adenosine tri-phosphate (ATP) binding cassette protein G2 (ABCG2), and epithelial cell adhesion molecule (EpCAM) are widely used, individually or in combination, to characterize some types of cancer stem cells. In this study we characterized the EpCAM+ retinoblastoma (RB) cells for their cancer stem-like properties in vitro. Additionally, we targeted RB tumor cells via redirecting T cells using bispecific EpCAM×CD3 antibody. Methods Flow cytometry was used to study the co-expression of EpCAM with putative cancer stem cell markers, such as CD44, CD24, and ABCG2, in RB primary tumors. In vitro methyl thiazol tetrazolium (MTT) assay, invasion assay, and neurosphere formation assay were performed to characterize EpCAM+ cells for their cancer stem/progenitor cell-like properties. We assessed the in vitro efficacy of bispecific EpCAM×CD3 antibody on RB tumor cell proliferation and validated the results by evaluating effector cytokine production in the culture medium with the ELISA method. Results EpCAM was co-expressed with all cancer stem cell markers (CD44, CD24, and ABCG2) in primary RB tumors. EpCAM+ cells showed significantly higher proliferative invasive potential and neurosphere formation in vitro compared to EpCAM– Y79 cells. EpCAM+ cells showed higher ?-catenin expression compared to EpCAM? cells. EpCAM×CD3 significantly retarded proliferation of RB primary tumor cells. EpCAM×CD3 effectively induced the secretion of effector cytokines, such as interferon (IFN)-?, tumor necrosis factor (TNF)-?, interleukin (IL)-10, IL-2, and transforming growth factor (TGF)-?1, and also perforin levels by pre-activated lymphocytes. Conclusions EpCAM might be a novel cancer stem cell marker in RB. EpCAM×CD3 antibody redirecting T cells to attack RB tumor cells may prove effective in RB management. Further preclinical studies are needed to confirm the initial findings of our study.

Mitra, Moutushy; Kandalam, Mallikarjuna; Harilal, Anju; Verma, Rama Shenkar; Krishnan, Uma Maheswari; Swaminathan, Sethuraman

2012-01-01

291

Adult Stem and Progenitor Cells  

NASA Astrophysics Data System (ADS)

The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out, with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether adult stem cells may have a greater plasticity than previously thought. Although cells with some features of embryonic stem cells that, among others, express Oct4, Nanog and SSEA1 are isolated from fresh tissue, it is not clear if the greater differentiation potential is acquired during cell culture. Moreover, adult more pluripotent cells do not have all pluripotent characteristics typical for embryonic stem cells. Recently, some elegant studies were published in which adult cells could be completely reprogrammed to embryonic stem cell-like cells by overexpression of some key transcription factors for pluripotency (Oct4, Sox2, Klf4 and c-Myc). It will be interesting for the future to investigate the exact mechanisms underlying this reprogramming and whether similar transcription factor pathways are present and/or can be activated in adult more pluripotent stem cells.

Geraerts, Martine; Verfaillie, Catherine M.

292

Effectiveness of Partner Social Support Predicts Enduring Psychological Distress after Hematopoietic Stem Cell Transplantation  

PubMed Central

Hematopoietic stem cell transplant survivors who are 1-3 years post-transplant are challenged by the need to resume valued social roles and activities—a task that may be complicated by enduring transplant-related psychological distress common in this patient population. The present study investigated whether transplant survivors who receive adequate social support from their spouse or intimate partner experience lower distress. Effects of receiving a greater quantity of partner support (a common approach to studying enacted support) were compared with effects of receiving more effective partner support (i.e., support that more closely matches their needs in terms of its quantity and quality). Men and women (N = 230) who were 1-3 years post-transplant completed measures of partner support quantity (Manne & Scholl, 2001), partner social support effectiveness (Rini & Dunkel Schetter, 2010), and psychological distress (Brief Symptom Inventory; Derogatis & Spencer, 1982). Potential medical and sociodemographic confounds were controlled in analyses. As hypothesized, survivors reported less distress when they received more effective partner support (p < .001). Quantity of partner support was not associated with distress (p = .23). An interaction revealed that when partner support was effective, the quantity of support survivors received was not associated with their distress (p=.90); however, when partner support was ineffective, receiving a greater quantity of partner support was associated with substantially elevated distress (p = .002). Findings suggest that clinical approaches to addressing or preventing enduring distress after HSCT should target features of partner support related to its appraised effectiveness.

Rini, Christine; Redd, William H.; Austin, Jane; Mosher, Catherine E.; Meschian, Yeraz Markarian; Isola, Luis; Scigliano, Eileen; Moskowitz, Craig H.; Papadopoulos, Esperanza; Labay, Larissa E.; Rowley, Scott; Burkhalter, Jack E.; Schetter, Christine Dunkel; DuHamel, Katherine N.

2013-01-01

293

Contrasting effect of perlecan on adipogenic and osteogenic differentiation of mesenchymal stem cells in vitro.  

PubMed

Perlecan, a basement membrane component, shows diverse functions in different organs and tissues. However, the role of perlecan in differentiation of mesenchymal stem cells (MSCs) has been barely investigated. In this study, we examined the effect of perlecan on adipogenic and osteogenic differentiation of MSCs?in vitro by adding extrinsic perlecan to culture media or blocking the function of intrinsic perlecan expressed into culture media by differentiating MSCs. Extrinsic perlecan suppressed adipogenic differentiation; however, it promoted osteogenic differentiation. These functions were further confirmed by a study of blocking intrinsic perlecan. Perlecan treated with heparitinase-I also showed the suppressive effect on adipogenic differentiation. In contrast, the promotive effect on osteogenic differentiation was found to be heparan sulfate-dependent. Intrinsic perlecan was suggested to be effective at the late stage of adipogenic differentiation by a study of perlecan-blocking performed at distinct periods, but was suggested to be effective at the early stage of osteogenic differentiation. Our results showed perlecan has contrasting effect on adipogenic and osteogenic differentiation of MSCs due to its diverse actions. Based on these outcomes, we recognized that employing extrinsic perlecan or blocking intrinsic perlecan is effective for regulating adipogenic and osteogenic differentiation of MSCs by restricting its direction. PMID:24000897

Nakamura, Ryosuke; Nakamura, Fumio; Fukunaga, Shigeharu

2014-03-01

294

History of Cancer Stem Cells  

Microsoft Academic Search

\\u000a It has been hypothesized for over 40 years that cancers contain the same cell populations as normal tissues: stem cells, proliferating\\u000a transit-amplifying cells, and terminally differentiated (mature cells). The properties of cancer stem cells include the ability\\u000a to transplant the tumor, the ability to grow in vitro and the ability to resist conventional therapies. The idea that cancer\\u000a arose from

Stewart Sell

295

Effect of NK4 Transduction in Bone Marrow-Derived Mesenchymal Stem Cells on Biological Characteristics of Pancreatic Cancer Cells  

PubMed Central

Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF) which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs) strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer.

Sun, Yun-Peng; Zhang, Ben-Long; Duan, Jian-Wen; Wu, Huan-Huan; Wang, Ben-Quan; Yu, Zheng-Ping; Yang, Wen-Jun; Shan, Yun-Feng; Zhou, Meng-Tao; Zhang, Qi-Yu

2014-01-01

296

Auraptene and its effects on the re-emergence of colon cancer stem cells.  

PubMed

Recent studies indicate that auraptene (7-geranyloxycoumarin, AUR), a geranyloxycoumarin extracted from fruits of edible plants belonging to the Rutaceae family, may represent a novel lead compound for dietary colon cancer chemoprevention in rodents. As a continuation of studies aimed to better depict the pharmacological effects and mechanism of action of the title natural compound, the current investigation was undertaken to determine whether AUR would be able to prevent the growth and sphere (surrogate tumors) formation of FOLFOX-resistant colon cancer cells that are highly enriched in cancer stem cells (CSCs). Our results demonstrate that AUR at a concentration of 10 ?M was able to inhibit the growth and formation of colonospheres of FOLFOX-resistant colon cancer HT-29 cells in vitro. The corresponding parental cells were also similarly affected by AUR at the same concentration level. The reduction in the growth and colonospheres formation in FOLFOX-resistant HT-29 was also associated with a concomitant decrease in phospho-epidermal growth factor receptor. These findings suggest that AUR could prevent the re-emergence of CSCs. PMID:22761031

Epifano, Francesco; Genovese, Salvatore; Miller, Rebecca; Majumdar, Adhip P N

2013-05-01

297

Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells.  

PubMed

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer. PMID:24710932

Peng, Gong-ling; Tian, Ye; Lu, Chong; Guo, Hui; Zhao, Xiang-wang; Guo, Ya-wen; Wang, Long-qiang; Du, Qiu-li; Liu, Chun-ping

2014-04-01

298

Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma.  

PubMed

We evaluated a new therapeutic strategy for malignant glioma, which combines intratumoral inoculation of mesenchymal stem cells (MSCs) expressing cytosine deaminase gene with 5-fluorocytosine (5-FC) administration. For in vitro and in vivo experiments, MSCs were transfected with adenovirus carrying either enhanced green fluorescent protein gene (AdexCAEGFP) or cytosine deaminase gene (AdexCACD), to establish MSC-expressing EGFP (MSC-EGFP) or CD (MSC-CD). Co-culture of 9L glioma cells with MSC-CD in a medium containing 5-FC resulted in a remarkable reduction in 9L cell viability. The migratory ability of MSC-EGFP toward 9L cells was demonstrated by double-chamber assay. For the in vivo study, rats harboring 9L brain tumors were inoculated with MSC-EGFP or MSC-CD. Immunohistochemistry of rat brain tumors inoculated with MSC-EGFP showed intratumoral distribution of MSC-EGFP. Survival analysis of rats bearing 9L gliomas treated with intratumoral MSC-CD and intraperitoneal 5-FC resulted in significant prolongation of survival compared with control animals. In conclusion, molecular therapy combining suicide gene therapy and MSCs as a targeting vehicle represents a potential new therapeutic approach for malignant glioma, both with respect to the antitumor potential of this system and its neuroprotective effect on normal brain tissue. PMID:22744211

Kosaka, H; Ichikawa, T; Kurozumi, K; Kambara, H; Inoue, S; Maruo, T; Nakamura, K; Hamada, H; Date, I

2012-08-01

299

Auraptene and its Effects on the Re-emergence of Colon Cancer Stem Cells  

PubMed Central

Recent studies indicate that auraptene (7-geranyloxycoumarin, AUR), a geranyloxycoumarin extracted from fruits of edible plants belonging to the Rutaceae family, may represent a novel lead compound for dietary colon cancer chemoprevention in rodents. As a continuation of studies aimed to better depict the pharmacological effects and mechanism of action of the title natural compound, the current investigation was undertaken to determine whether AUR would be able to prevent the growth and sphere (surrogate tumors) formation of FOLFOX-resistant colon cancer cells that are highly enriched in cancer stem cells (CSCs). Our results demonstrate that AUR at a concentration of 10 µM was able to inhibit the growth and formation of colonospheres of FOLFOX-resistant colon cancer HT-29 cells in vitro. The corresponding parental cells were also similarly affected by AUR at the same concentration level. The reduction in the growth and colonospheres formation in FOLFOX-resistant HT-29 was also associated with a concomitant decrease in phospho-epidermal growth factor receptor (pEGFR). These findings suggest that AUR could prevent the re-emergence of CSCs.

Epifano, Francesco; Genovese, Salvatore; Miller, Rebecca; Majumdar, Adhip P. N.

2012-01-01

300

Effect of the Environmental Pollutant Hexachlorobenzene (HCB) on the Neuronal Differentiation of Mouse Embryonic Stem Cells  

PubMed Central

Exposure to persistent environmental pollutants may constitute an important factor on the onset of a number of neurological disorders such as autism, Parkinson’s disease, and Attention Deficit Disorder (ADD), which have also been linked to reduced GABAergic neuronal function. GABAergic neurons produce ?-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the brain. However, the lack of appropriate models has hindered the study of suspected environmental pollutants on GABAergic function. In this work, we have examined the effect of hexachlorobenzene (HCB), a persistent and bioaccumulative environmental pollutant, on the function and morphology of GABAergic neurons generated in vitro from mouse embryonic stem (ES) cells. We observed that: (1) treatment with 0.5 nM HCB did not affect cell viability, but affected the neuronal differentiation of ES cells; (2) HCB induced the production of reactive oxygen species (ROS); and (3) HCB repressed neurite outgrowth in GABAergic neurons, but this effect was reversed by the ROS scavenger N-acetylcysteine (NAC). Our study also revealed that HCB did not significantly interfere with the function of K+ ion channels in the neuronal soma, which indicates that this pollutant does not affect the maturation of the GABAergic neuronal soma. Our results suggest a mechanism by which environmental pollutants interfere with normal GABAergic neuronal function and may promote the onset of a number of neurological disorders such as autism and ADD.

Addae, Cynthia; Cheng, Henrique; Martinez-Ceballos, Eduardo

2013-01-01

301

Effect of the environmental pollutant hexachlorobenzene (HCB) on the neuronal differentiation of mouse embryonic stem cells.  

PubMed

Exposure to persistent environmental pollutants may constitute an important factor on the onset of a number of neurological disorders such as autism, Parkinson's disease, and Attention Deficit Disorder (ADD), which have also been linked to reduced GABAergic neuronal function. GABAergic neurons produce ?-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the brain. However, the lack of appropriate models has hindered the study of suspected environmental pollutants on GABAergic function. In this work, we have examined the effect of hexachlorobenzene (HCB), a persistent and bioaccumulative environmental pollutant, on the function and morphology of GABAergic neurons generated in vitro from mouse embryonic stem (ES) cells. We observed that: (1) treatment with 0.5 nM HCB did not affect cell viability, but affected the neuronal differentiation of ES cells; (2) HCB induced the production of reactive oxygen species (ROS); and (3) HCB repressed neurite outgrowth in GABAergic neurons, but this effect was reversed by the ROS scavenger N-acetylcysteine (NAC). Our study also revealed that HCB did not significantly interfere with the function of K+ ion channels in the neuronal soma, which indicates that this pollutant does not affect the maturation of the GABAergic neuronal soma. Our results suggest a mechanism by which environmental pollutants interfere with normal GABAergic neuronal function and may promote the onset of a number of neurological disorders such as autism and ADD. PMID:24157519

Addae, Cynthia; Cheng, Henrique; Martinez-Ceballos, Eduardo

2013-10-01

302

Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors  

PubMed Central

Background Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods. Results We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as ?-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration. Conclusions We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also for in vitro applications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.

2013-01-01

303

Genetic approaches identify adult pituitary stem cells  

Microsoft Academic Search

Adult tissues undergo continuous cell turnover in response to stress, damage, or physiological demand. New differentiated cells are generated from dedicated or facultative stem cells or from self-renewing differentiated cells. Here we describe a different stem cell strategy for tissue maintenance, distinct from that observed for dedicated or facultative stem cells. We report the presence of nestin-expressing adult stem cells

Anatoli S. Gleiberman; Tatyana Michurina; Juan M. Encinas; Jose L. Roig; Peter Krasnov; Francesca Balordi; Gord Fishell; Michael G. Rosenfeld; Grigori Enikolopov

2008-01-01

304

Mesenchymal stem cells regulate the proliferation and differentiation of neural stem cells through Notch signaling  

Microsoft Academic Search

The effects of mesenchymal stem cells (MSCs) on proliferation and cell fate determination of neural stem cells (NSCs) have been investigated. NSCs were co-cultured with MSCs or NIH3T3 cells using an in vitro transwell system. After 4 days, immunofluorescence staining showed that the number of cells positive for the cell proliferation antigen, ki-67, in neurospheres in MSCs was greater than

Yang Wang; Wei Tu; Yuanlei Lou; An Xie; Xianliang Lai; Fei Guo; Zhifeng Deng

2009-01-01

305

FDA Warns About Stem Cell Claims  

MedlinePLUS

... Biologics Articulos en Espanol FDA Warns About Stem Cell Claims Search the Consumer Updates Section Researchers hope ... forming system. back to top Regulation of Stem Cells FDA regulates stem cells in the U.S. to ...

306

What's It Like to Donate Stem Cells?  

MedlinePLUS

... learn more What’s it like to donate stem cells? People usually volunteer to donate stem cells for ... autologous transplant. If you want to donate stem cells for someone else People who want to donate ...

307

Sex and stem cell research  

Microsoft Academic Search

This paper discusses the ethical and political issues that stem cell research faces. Stem cell research holds great promise for treating serious diseases but does so by using materials from the very beginning of life. There is a division among different sects of society as some see a important ethical principle being threatened, while others see scientific progress being threatened

John Fielder

2006-01-01

308

Stem Cells from Fetal Membranes  

Microsoft Academic Search

Stem cells that can be derived from fetal membranes represent an exciting field of research that bears tremendous potential for developmental biology and regenerative medicine. In this report we summarize contributions to a workshop in which newest insights into the characteristics, subtypes and molecular determinants of stem cells from trophoblast and endometrial tissues were presented.

M. Hemberger; W. Yang; D. Natale; Thomas L. Brown; C. Dunk; C. E. Gargett; S. Tanaka

2008-01-01

309

Plasticity of Adult Stem Cells  

Microsoft Academic Search

Recent years have seen much excitement over the possibility that adult mammalian stem cells may be capable of differentiating across tissue lineage boundaries, and as such may represent novel, accessible, and very versatile effectors of therapeutic tissue regeneration. Yet studies proposing such “plasticity” of adult somatic stem cells remain controversial, and in general, existing evidence suggests that in vivo such

Amy J Wagers; Irving L Weissman

2004-01-01

310

Attributes of adult stem cells.  

PubMed

While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organ-specific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts. PMID:19085991

Alison, M R; Islam, S

2009-01-01

311

Effect of Lithium Chloride on Proliferation and Bone Differentiation of Rat Marrow-Derived Mesenchymal Stem Cells in Culture  

Microsoft Academic Search

Objective(s) It is believed that the mesenchymal stem cell (MSC) differentiation and proliferation are the results of activation of wnt signaling pathway. On the other hand, lithium chloride is reported to be able to activate this pathway. The objective of this study was to investigate the effect of lithium on in vitro proliferation and bone differentiation of marrow-derived MSC. Materials

Mohamadreza Baghaban Eslaminejad; Mahmood Talkhabi; Bahman Zeynali

2008-01-01

312

Photographic Framing in the Stem Cell Debate: Integrating Eye-Tracking Data for a New Dimension of Media Effects Research  

Microsoft Academic Search

A growing body of research examines media framing of key scientific issues of our time, specifically, those issues that include political and moral components, such as global climate change and stem cell research. In regard to the mass media, framing refers to the process by which the media organize and make sense of the news, which has an effect on

Nicole S. Dahmen

2012-01-01

313

A Double Mechanism for the Mesenchymal Stem Cells' Positive Effect on Pancreatic Islets  

PubMed Central

The clinical usability of pancreatic islet transplantation for the treatment of type I diabetes, despite some encouraging results, is currently hampered by the short lifespan of the transplanted tissue. In vivo studies have demonstrated that co-transplantation of Mesenchymal Stem Cells (MSCs) with transplanted pancreatic islets is more effective with respect to pancreatic islets alone in ensuring glycemia control in diabetic rats, but the molecular mechanisms of this action are still unclear. The aim of this study was to elucidate the molecular mechanisms of the positive effect of MSCs on pancreatic islet functionality by setting up direct, indirect and mixed co-cultures. MSCs were both able to prolong the survival of pancreatic islets, and to directly differentiate into an “insulin-releasing” phenotype. Two distinct mechanisms mediated these effects: i) the survival increase was observed in pancreatic islets indirectly co-cultured with MSCs, probably mediated by the trophic factors released by MSCs; ii) MSCs in direct contact with pancreatic islets started to express Pdx1, a pivotal gene of insulin production, and then differentiated into insulin releasing cells. These results demonstrate that MSCs may be useful for potentiating pancreatic islets' functionality and feasibility.

Scuteri, Arianna; Donzelli, Elisabetta; Rodriguez-Menendez, Virginia; Ravasi, Maddalena; Monfrini, Marianna; Bonandrini, Barbara; Figliuzzi, Marina; Remuzzi, Andrea; Tredici, Giovanni

2014-01-01

314

Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration.  

PubMed

Mesenchymal stem cell (MSC) implantation has been shown previously to arrest disc degeneration. This study aims to assess the effect of severity of disc degeneration on the ability of MSCs to arrest the degeneration. Disc degeneration was induced in New Zealand white rabbits at lumbar levels by annular puncture. The degeneration was allowed to progress for 1 month (early group) or 7 months (late group), followed by intradiscal injection of autologous MSCs. For disc levels that received MSCs treatment, 1 x 10(5) BrdU-labeled MSCs were injected per disc level. For the early group, MSC-injection had no significant effects on disc height or the progression of disc degeneration. For the late group, although the MSC-injected discs displayed lower disc heights than the control discs, they were significantly less degenerated together with near normal level of proteoglycan in localized areas. This is the first pilot study to demonstrate that severity of degeneration can influence the therapeutic effect of MSCs. Future studies of cell-based intervertebral disc regeneration should be carefully controlled in the context of stage of disc degeneration. PMID:18293174

Ho, Grace; Leung, Victor Y L; Cheung, Kenneth M C; Chan, Danny

2008-01-01

315

Effects of chemotherapeutic agents for testicular cancer on rat spermatogonial stem/progenitor cells.  

PubMed

Spermatogonial stem cells (SSCs) are responsible for the production of spermatozoa throughout adulthood and for the recovery of spermatogenesis following exposure to cytotoxic agents. Previously, we have shown that the combined administration of bleomycin, etoposide, and cisplatin (BEP) used in the treatment of testicular cancer causes impaired spermatogenesis and reduced sperm production in the rat. However, definitive evidence about the potential impact of such chemotherapy on SSCs is still lacking. The objective of this study was to determine whether chronic exposure to BEP treatment causes adverse effects on rat SSC activity. We first investigated the effects of BEP treatment on the clonal organization of undifferentiated spermatogonia by staining whole-mount preparations of rat seminiferous tubules for GFRA1 and ZBTB16 (previously known as PLZF), 2 established markers of undifferentiated spermatogonia. We found that BEP treatment drastically reduced the number of A-aligned spermatogonia while sparing A-single and A-paired cells from the effect. Next, we determined the SSC activity following BEP exposure. Adult transgenic rats carrying EGFP expression in the germ line were treated with BEP for 9 weeks, and SSCs were quantified using spermatogonial transplantation. We found that BEP treatment significantly decreased SSC numbers, which were restored to the control level after a 9-week recovery period. These results demonstrate that BEP treatment transiently affects the activity of rat SSCs. PMID:21088230

Marcon, Ludovic; Zhang, Xiangfan; Hales, Barbara F; Robaire, Bernard; Nagano, Makoto C

2011-01-01

316

A double mechanism for the mesenchymal stem cells' positive effect on pancreatic islets.  

PubMed

The clinical usability of pancreatic islet transplantation for the treatment of type I diabetes, despite some encouraging results, is currently hampered by the short lifespan of the transplanted tissue. In vivo studies have demonstrated that co-transplantation of Mesenchymal Stem Cells (MSCs) with transplanted pancreatic islets is more effective with respect to pancreatic islets alone in ensuring glycemia control in diabetic rats, but the molecular mechanisms of this action are still unclear. The aim of this study was to elucidate the molecular mechanisms of the positive effect of MSCs on pancreatic islet functionality by setting up direct, indirect and mixed co-cultures. MSCs were both able to prolong the survival of pancreatic islets, and to directly differentiate into an "insulin-releasing" phenotype. Two distinct mechanisms mediated these effects: i) the survival increase was observed in pancreatic islets indirectly co-cultured with MSCs, probably mediated by the trophic factors released by MSCs; ii) MSCs in direct contact with pancreatic islets started to express Pdx1, a pivotal gene of insulin production, and then differentiated into insulin releasing cells. These results demonstrate that MSCs may be useful for potentiating pancreatic islets' functionality and feasibility. PMID:24416216

Scuteri, Arianna; Donzelli, Elisabetta; Rodriguez-Menendez, Virginia; Ravasi, Maddalena; Monfrini, Marianna; Bonandrini, Barbara; Figliuzzi, Marina; Remuzzi, Andrea; Tredici, Giovanni

2014-01-01

317

Lasers, stem cells, and COPD  

PubMed Central

The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.

2010-01-01

318

Stem cell research for male infertility  

Microsoft Academic Search

Stem cells have the ability both to differentiate into numerous tissues and to self-renew. Because of these unique properties,\\u000a stem cells are promising candidates for use in regenerative medicine. Among stem cell types, embryonic stem (ES) cells have\\u000a been the most studied; however, alternatives such as induced pluripotent stem cells or other adult stem cells are now being\\u000a established. In

Hideyuki Kobayashi; Koichi Nakajima

319

Potent Biology: Stem Cells, Cloning, and Regeneration  

NSDL National Science Digital Library

This lecture series, from the Howard Hughes Medical Institute Biointeractive project, features five lectures: "Understanding Embryonic Stem Cells," "Adult Stem Cells and Regeneration," "Coaxing Embryonic Stem Cells," "Stem Cells and the End of Aging," and "Stem Cell Research: Policies and Ethics." Each lecture, available in Flash and RealPlayer format, contains interviews, animations, and narratives to help students understand more about stem cells, their applications, and further research.

2012-11-05

320

The effect of centrifugation condition on mature adipocytes and adipose stem cell viability.  

PubMed

Different researchers have recommended different lipoaspirate centrifugation speeds and times, probably due to the limits in fat cell viability assays. We assessed fat cell viability using a fluorescein diacetate and propidium iodide (FDA-PI) stain and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay after harvesting syringe liposuction and spun with different centrifugation speeds to determine the optimal conditions. Lipoaspirates, harvested from 13 donors, were transferred into a centrifuge tube and spun at 1000, 3000, and 4000 rpm for 3 minutes. Mature adipocytes and adipose stem cells were isolated and tested with a direct counting of FDA-PI-stained cells under fluorescence microscope and XTT assay. We incubated adipocytes and adipose stem cells for 1 day and 3 days, and we compared both of them with fresh samples to evaluate the influence of culturing condition on fat cell viability. Centrifugation speeds from 1000 rpm to 4000 rpm for 3 minutes showed no change in the percentage of adipocytes and adipose stem cell viability not only in the fresh samples but also in the cultured samples (1 day and 3 days). Centrifugation speeds under 4000 rpm do not change the percentage of fat cell viability. To differentiate viable cells from dying or dead mature adipocytes and oil accurately, combinations of viability tests are essential. PMID:23636113

Son, Daegu; Choi, Taehyun; Yeo, Hyeonjung; Kim, Junhyung; Han, Kihwan

2014-05-01

321

Stem cell mechanics: Auxetic nuclei  

NASA Astrophysics Data System (ADS)

The nuclei of naive mouse embryonic stem cells that are transitioning towards differentiation expand when the cells are stretched and contract when they are compressed. What drives this auxetic phenotype is, however, unclear.

Wang, Ning

2014-06-01

322

CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells  

SciTech Connect

Here, the effect of CD14{sup +} monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-{gamma} (IFN-{gamma}) secretion capacities of CD4{sup +} and CD8{sup +} T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E{sub 2} (PGE{sub 2}) as an important soluble mediator. CD14{sup +} monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1{beta}, either exogenously added or produced by CD14{sup +} monocytes in culture, could trigger expression of high levels of PGE{sub 2} by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE{sub 2} expression, but also reversed the promotional effect of CD14{sup +} monocytes and partially restored CD4{sup +} and CD8{sup +} T cell proliferation and IFN-{gamma} secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

Wang, Ding, E-mail: qqhewd@gmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China) [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Chen, Ke, E-mail: chenke_59@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China) [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Du, Wei Ting, E-mail: duwtpumc@yahoo.com.cn [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); Han, Zhi-Bo, E-mail: zhibohan@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China) [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Ren, He, E-mail: knifesharp2000@hotmail.com [National Engineering Research Center of Cell Products, AmCellGene Co. Ltd, TEDA, Tianjin (China)] [National Engineering Research Center of Cell Products, AmCellGene Co. Ltd, TEDA, Tianjin (China); Chi, Ying, E-mail: caizhuying@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China) [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); and others

2010-09-10

323

Neuroprotective effects of amlodipine besylate and benidipine hydrochloride on oxidative stress-injured neural stem cells.  

PubMed

Hypertension is associated with oxidative stress. Amlodipine besylate (AB) and benidipine hydrochloride (BH), which are Ca(2+) antagonists, have been reported to reduce oxidative stress. In this study, we examined the neuroprotective effects of AB and BH on oxidative stress-injured neural stem cells (NSCs), with a focus on the phosphatidylinositol 3-kinase (PI3K) pathway and the extracellular signal-regulated kinase (ERK) pathway. After treatment with H2O2, the viability of NSCs decreased in a concentration-dependent manner; however, co-treatment with AB or BH restored the viability of H2O2-injured NSCs. H2O2 increased free radical production and apoptosis in NSCs, whereas co-treatment with AB or BH attenuated these effects. To evaluate the effects of AB or BH on the H2O2-inhibited proliferation of NSCs, we performed BrdU labeling and colony formation assays and found that NSC proliferation decreased upon H2O2 treatment but that combined treatment with AB or BH restored this proliferation. Western blot analysis showed that AB and BH increased the expression of cell survival-related proteins that were linked with the PI3K and ERK pathways but decreased the expression of cell death-related proteins. To investigate whether the PI3K and ERK pathways were directly involved in the neuroprotective effects of AB and BH on H2O2-treated NSCs, NSCs were pretreated with the PI3K inhibitor, LY294002, or the ERK inhibitor, FR180204, which significantly blocked the effects of AB and BH. Together, our results suggest that AB and BH restore the H2O2-inhibited viability and proliferation of NSCs by inhibiting oxidative stress and by activating the PI3K and ERK pathways. PMID:24440775

Choi, Na-Young; Choi, Hojin; Park, Hyun-Hee; Lee, Eun-Hye; Yu, Hyun-Jeung; Lee, Kyu-Yong; Joo Lee, Young; Koh, Seong-Ho

2014-03-10

324

Effects of oxytocin on cardiomyocyte differentiation from mouse embryonic stem cells.  

PubMed

This study sought to investigate the presence of oxytocin receptors and the possible biological role of oxytocin as an effective factor in the differentiation of embryonic stem cells (ESCs) into cardiomyocytes. Mouse ESCs were cultivated in hanging drops to form embryoid bodies (EBs). The EBs were then treated with and without oxytocin (experimental and control groups). Up to 30 days after plating, contraction and beating frequency were monitored and evaluated daily. The growth characteristics of the ESC-derived cardiomyocytes were assessed by cardioactive drugs, immunocytochemistry, transmission electron microscopy (TEM) and reverse transcription-polymerase chain reaction (RT-PCR). In the experimental group, the percentage of the EBs with spontaneous contraction was significantly increased from 17th day onward. The spontaneous beating frequency of each EB in both groups was also changed with cardioactive drugs such as Bay K, carbachol, isopernaline and phenylephrine. However, in the experimental group, changes with isopernaline were more pronounced at the early and intermediate stages of cardiomyocyte development. The beating cells of both groups, stained positive with anti alpha-actinin, desmin, cardiac troponin I and connexin antibodies, and revealed similar ultrastructural features. Oxytocin receptors were detected on the ESCs and derived-differentiated cells. In addition, cardiac-specific genes such as cardiac alpha- and beta-myosin heavy chain, myosin light chain-2v, and atrial natriuretic factor were also detected in the ESC-derived differentiated cells of both groups. In the experimental group, all the specific genes, with the exception of alpha-myosin heavy chain, were more pronounced at the early stage of cardiomyocyte development. In conclusion, oxytocin has receptors on undifferentiated ESCs and derived differentiated cells, and in spite of better improvement of the EBs with spontaneous contraction, it can only promote the early maturation of ESC-derived cardiomyocytes in terms of chronotropic responses and expression of cardiac-specific genes, and have no effect on ultrastructural characteristics of cardiomyocytes in any stage of development. PMID:17034884

Hatami, Leili; Valojerdi, Mojtaba Rezazadeh; Mowla, Seyed Javad

2007-04-12

325

Hematopoietic stem cell compartment: Acute and late effects of radiation therapy an chemotherapy  

SciTech Connect

The bone marrow is an important dose-limiting cell renewal tissue for chemotherapy, wide-field irradiation, and autologous bone marrow transplantion. Over the past 5-10 years a great deal has been discovered about the hematopoietic stem cell compartment. Although the toxicity associated with prolonged myelosuppression continue to limit the wider use of chemotherapy and irradiation, ways are being discovered to circumvent this toxicity such as with the increasing use of cytokines. This review describes what is known of how chemotherapy and irradiation damage stem cells and the microenvironment, how cytokines protect hematopoietic cells from radiation damage and speed marrow recovery after chemotherapy or marrow transplantation, and how various types of blood marrow cells contribute to engraftment and long-term hematopoiesis after high doses of cytotoxic agents and/or total body irradiation. 167 refs., 7 figs., 6 tabs.

Mauch, P. [Harvard Medical School, Boston, MA (United States)] [Harvard Medical School, Boston, MA (United States); Constine, L. [Univ. of Rochester Medical School, NY (United States)] [Univ. of Rochester Medical School, NY (United States); Greenberger, J. [Univ. of Pittsburgh Medical Center, PA (United States)] [and others] [Univ. of Pittsburgh Medical Center, PA (United States); and others

1995-03-30

326

Contrasting hypoxic effects on breast cancer stem cell hierarchy is dependent on ER-? status.  

PubMed

Tumor hypoxia is often linked to decreased survival in patients with breast cancer and current therapeutic strategies aim to target the hypoxic response. One way in which this is done is by blocking hypoxia-induced angiogenesis. Antiangiogenic therapies show some therapeutic potential with increased disease-free survival, but these initial promising results are short lived and followed by tumor progression. We hypothesized that this may be due to altered cancer stem cell (CSC) activity resulting from increased tumor hypoxia. We studied the effects of hypoxia on CSC activity, using in vitro mammosphere and holoclone assays as well as in vivo limiting dilution experiments, in 13 patient-derived samples and four cell lines. There was a HIF-1?-dependent CSC increase in ER-?-positive cancers following hypoxic exposure, which was blocked by inhibition of estrogen and Notch signaling. A contrasting decrease in CSC was seen in ER-?-negative cancers. We next developed a xenograft model of cell lines and patient-derived samples to assess the hypoxic CSC response. Varying sizes of xenografts were collected and analyzed for HIF1-? expression and CSC. The same ER-?-dependent contrasting hypoxic-CSC response was seen validating the initial observation. These data suggest that ER-?-positive and negative breast cancer subtypes respond differently to hypoxia and, as a consequence, antiangiogenic therapies will not be suitable for both subgroups. PMID:23248117

Harrison, Hannah; Rogerson, Lynsey; Gregson, Hannah J; Brennan, Keith R; Clarke, Robert B; Landberg, Göran

2013-02-15

327

Neuroprotective effects of mesenchymal stem cells through autophagy modulation in a parkinsonian model.  

PubMed

Autophagy is a major degradation pathway for abnormal aggregated proteins and organelles that cause various neurodegenerative diseases. Current evidence suggests a central role for autophagy in pathogenesis of Parkinson's disease, and that dysfunction in the autophagic system may lead to ?-synuclein accumulation. In the present study, we investigated whether mesenchymal stem cells (MSCs) would enhance autophagy and thus exert a neuroprotective effect through the modulation of ?-synuclein in parkinsonian models. In MPP(+)-treated neuronal cells, coculture with MSCs increased cellular viability, attenuated expression of ?-synuclein, and enhanced the number of LC3-II-positive autophagosomes compared with cells treated with MPP(+) only. In an MPTP-treated animal model of Parkinson's disease, MSC administration significantly increased final maturation of late autophagic vacuoles, fusion with lysosomes. Moreover, MSC administration significantly reduced the level of ?-synuclein in dopaminergic neurons, which was elevated in MPTP-treated mice. These results suggest that MSC treatment significantly enhances autophagolysosome formation and may modulate ?-synuclein expression in parkinsonian models, which may lead to increased neuronal survival in the presence of neurotoxins. PMID:24629674

Park, Hyun Jung; Shin, Jin Young; Kim, Ha Na; Oh, Se Hee; Lee, Phil Hyu

2014-08-01

328

Effects of ECM protein mimetics on adhesion and proliferation of chorion derived mesenchymal stem cells.  

PubMed

Background: We evaluated the effects of fibronectin, collagen, cadherin, and laminin based extracellular matrix (ECM) protein mimetics coated with mussel derived adhesive protein (MAP) on adhesion and proliferation of chorionic mesenchymal stem cells (cMSCs). Methods: Human placental chorionic tissues from term third-trimester pregnancies (n=3) were used. The cMSCs were cultured on rationally designed ECM protein mimetics coated with MAP on plastic surfaces with the addition of reduced fetal bovine serum (0.5%, 1% FBS). Adhesion capabilities were monitored by a real time cell analysis system (RTCA) utilizing an impedance method. Proliferation capabilities were monitored by RTCA and MTS assay. Results: Of the ECM protein mimetics tested, GRGDSP(FN) coated surfaces exhibited the highest adhesion and proliferation capabilities on RTCA at FBS concentration of 0.5% and 1%. When 0.5% FBS was added to ECM protein mimetics during the MTS assay, GRGDSP(FN), REDV(FN), and collagen mimetics, GPKGAAGEPGKP(ColI) showed higher cMSCs proliferation compared with the control. When 1% FBS was added, GRGDSP(FN) and TAIPSCPEGTVPLYS(ColIV) showed significant cMSCs proliferation capacity. Conclusions: Fibronectin mimetics, GRGDSP(FN) amino acid sequence showed the highest adhesion and proliferation capabilities. In addition, results from RTCA assessment of cell viability correlated well with the tetrazolium-based MTS assay. PMID:24516355

Kim, Ji-Hyun; Jekarl, Dong Wook; Kim, Myungshin; Oh, Eun-Jee; Kim, Yonggoo; Park, In Yang; Shin, Jong Chul

2014-01-01

329

Effects of ECM Protein Mimetics on Adhesion and Proliferation of Chorion Derived Mesenchymal Stem Cells  

PubMed Central

Background: We evaluated the effects of fibronectin, collagen, cadherin, and laminin based extracellular matrix (ECM) protein mimetics coated with mussel derived adhesive protein (MAP) on adhesion and proliferation of chorionic mesenchymal stem cells (cMSCs). Methods: Human placental chorionic tissues from term third-trimester pregnancies (n=3) were used. The cMSCs were cultured on rationally designed ECM protein mimetics coated with MAP on plastic surfaces with the addition of reduced fetal bovine serum (0.5%, 1% FBS). Adhesion capabilities were monitored by a real time cell analysis system (RTCA) utilizing an impedance method. Proliferation capabilities were monitored by RTCA and MTS assay. Results: Of the ECM protein mimetics tested, GRGDSP(FN) coated surfaces exhibited the highest adhesion and proliferation capabilities on RTCA at FBS concentration of 0.5% and 1%. When 0.5% FBS was added to ECM protein mimetics during the MTS assay, GRGDSP(FN), REDV(FN), and collagen mimetics, GPKGAAGEPGKP(ColI) showed higher cMSCs proliferation compared with the control. When 1% FBS was added, GRGDSP(FN) and TAIPSCPEGTVPLYS(ColIV) showed significant cMSCs proliferation capacity. Conclusions: Fibronectin mimetics, GRGDSP(FN) amino acid sequence showed the highest adhesion and proliferation capabilities. In addition, results from RTCA assessment of cell viability correlated well with the tetrazolium-based MTS assay.

Kim, Ji-Hyun; Jekarl, Dong Wook; Kim, Myungshin; Oh, Eun-Jee; Kim, Yonggoo; Park, In Yang; Shin, Jong Chul

2014-01-01

330

Stem Cells for Myocardial Regeneration  

Microsoft Academic Search

Abstract—Stem cells are being investigated for their potential use in regenerative medicine. A series of remarkable studies suggested that adult stem cells undergo novel patterns of development,by a process referred to as transdifferentiation or plasticity. These observations fueled an exciting period of discovery and high expectations followed by controversy that emerged from data suggesting cell-cell fusion as an alternate interpretation

Toren Finkel; Roberto Bolli; Donald Orlic; Jonathan M. Hill; Andrew E. Arai

2010-01-01

331

Plasticity of epidermal stem cells  

Microsoft Academic Search

The keratinocyte cell compartment in the continuously renewing epidermis of the skin is maintained by undifferentiated, self-renewing\\u000a stem cells. We show that a small subpopulation of epidermal stem cells (EpiSCs) have the capacity to integrate into multiple\\u000a tissues. These EpiSCs can change their phenotype in direct response of changes in cytokines in vitro, changes in cocultured\\u000a cells, after injection into

Jackie R. Bickenbach; Matthew M. Stern

2005-01-01

332

Effects of Genetically Engineered Stem Cells Expressing Cytosine Deaminase and Interferon-Beta or Carboxyl Esterase on the Growth of LNCaP Prostate Cancer Cells.  

PubMed

The risk of prostate cancer has been increasing in men by degrees. To develop a new prostate cancer therapy, we used a stem cell-derived gene directed prodrug enzyme system using human neural stem cells (hNSCs) that have a tumor-tropic effect. These hNSCs were transduced with the therapeutic genes for bacterial cytosine deaminase (CD), alone or in combination with the one encoding human interferon-beta (IFN-?) or rabbit carboxyl esterase (CE) to generate HB1.F3.CD, HB1.F3.CD.IFN-?, and HB1.F3.CE cells, respectively. CD enzyme can convert the prodrug 5-fluorocytosine (5-FC) into the activated form 5-fluorouracil (5-FU). In addition, CE enzyme can convert the prodrug CPT-11 into a toxic agent, SN-38. In our study, the human stem cells were found to migrate toward LNCaP human prostate cancer cells rather than primary cells. This phenomenon may be due to interactions between chemoattractant ligands and receptors, such as VEGF/VEGFR2 and SCF/c-Kit, expressed as cancer and stem cells, respectively. The HB1.F3.CE, HB.F3.CD, or HB1.F3.CD.IFN-? cells significantly reduced the LNCaP cell viability in the presence of the prodrugs 5-FC or CPT-11. These results indicate that stem cells expressing therapeutic genes can be used to develop a new strategy for selectively treating human prostate cancer. PMID:23202910

Yi, Bo-Rim; Hwang, Kyung-A; Kim, Yun-Bae; Kim, Seung U; Choi, Kyung-Chul

2012-01-01

333

Ectopic ?-catenin Expression Partially Mimics the Effects of Stabilized ?-catenin on Embryonic Stem Cell Differentiation  

PubMed Central

?-catenin, an adherens junction component and key Wnt pathway effector, regulates numerous developmental processes and supports embryonic stem cell (ESC) pluripotency in specific contexts. The ?-catenin homologue ?-catenin (also known as Plakoglobin) is a constituent of desmosomes and adherens junctions and may participate in Wnt signaling in certain situations. Here, we use ?-catenin(+/+) and ?-catenin(?/?) mouse embryonic stem cells (mESCs) to investigate the role of ?-catenin in Wnt signaling and mESC differentiation. Although ?-catenin protein is markedly stabilized upon inhibition or ablation of GSK-3 in wild-type (WT) mESCs, efficient silencing of its expression in these cells does not affect ?-catenin/TCF target gene activation after Wnt pathway stimulation. Nonetheless, knocking down ?-catenin expression in WT mESCs appears to promote their exit from pluripotency in short-term differentiation assays. In ?-catenin(?/?) mESCs, GSK-3 inhibition does not detectably alter cytosolic ?-catenin levels and does not activate TCF target genes. Intriguingly, ?-catenin/TCF target genes are induced in ?-catenin(?/?) mESCs overexpressing stabilized ?-catenin and the ability of these genes to be activated upon GSK-3 inhibition is partially restored when wild-type ?-catenin is overexpressed in these cells. This suggests that a critical threshold level of total catenin expression must be attained before there is sufficient signaling-competent ?-catenin available to respond to GSK-3 inhibition and to regulate target genes as a consequence. WT mESCs stably overexpressing ?-catenin exhibit robust Wnt pathway activation and display a block in tri-lineage differentiation that largely mimics that observed upon overexpression of ?-catenin. However, ?-catenin overexpression appears to be more effective than ?-catenin overexpression in sustaining the retention of markers of naïve pluripotency in cells that have been subjected to differentiation-inducing conditions. Collectively, our study reveals a function for ?-catenin in the regulation of mESC differentiation and has implications for human cancers in which ?-catenin is mutated and/or aberrantly expressed.

Paez-Parent, Sabrina; Mahmood, Sharmeen; Polena, Enio; Cooney, Austin J.; Doble, Bradley W.

2013-01-01

334

Mathematical modelling of adult hippocampal neurogenesis: effects of altered stem cell dynamics on cell counts and bromodeoxyuridine-labelled cells  

PubMed Central

In the adult hippocampus, neurogenesis—the process of generating mature granule cells from adult neural stem cells—occurs throughout the entire lifetime. In order to investigate the involved regulatory mechanisms, knockout (KO) experiments, which modify the dynamic behaviour of this process, were conducted in the past. Evaluating these KOs is a non-trivial task owing to the complicated nature of the hippocampal neurogenic niche. In this study, we model neurogenesis as a multicompartmental system of ordinary differential equations based on experimental data. To analyse the results of KO experiments, we investigate how changes of cell properties, reflected by model parameters, influence the dynamics of cell counts and of the experimentally observed counts of cells labelled by the cell division marker bromodeoxyuridine (BrdU). We find that changing cell proliferation rates or the fraction of self-renewal, reflecting the balance between symmetric and asymmetric cell divisions, may result in multiple time phases in the response of the system, such as an initial increase in cell counts followed by a decrease. Furthermore, these phases may be qualitatively different in cells at different differentiation stages and even between mitotically labelled cells and all cells existing in the system.

Ziebell, Frederik; Martin-Villalba, Ana; Marciniak-Czochra, Anna

2014-01-01

335

The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis.  

PubMed

Mesenchymal stem cells (MSCs) are being explored extensively as a promising treatment for autoimmune diseases. We have recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we examined further the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on T helper type 1 (Th1) and Th17 cells and how long the inhibitory effect lasted, in order to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs decreased the production of Th1 and Th17 cytokines significantly, while the production of Th2 and regulatory T cell (T(reg)) cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-?] was elevated during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humour (AqH) were reduced in MSC-treated rats. Moreover, the ratio of Th17/T(reg) cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can regulate negatively both Th1 and Th17 responses and restore the balance of Th17/T(regs) in the whole course of EAU, which is important for the regression of the disease. PMID:23607419

Li, G; Yuan, L; Ren, X; Nian, H; Zhang, L; Han, Z C; Li, X; Zhang, X

2013-07-01

336

The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis  

PubMed Central

Mesenchymal stem cells (MSCs) are being explored extensively as a promising treatment for autoimmune diseases. We have recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we examined further the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on T helper type 1 (Th1) and Th17 cells and how long the inhibitory effect lasted, in order to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs decreased the production of Th1 and Th17 cytokines significantly, while the production of Th2 and regulatory T cell (Treg) cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-?] was elevated during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humour (AqH) were reduced in MSC-treated rats. Moreover, the ratio of Th17/Treg cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can regulate negatively both Th1 and Th17 responses and restore the balance of Th17/Tregs in the whole course of EAU, which is important for the regression of the disease.

Li, G; Yuan, L; Ren, X; Nian, H; Zhang, L; Han, Z C; Li, X; Zhang, X

2013-01-01

337

Evaluating the Effect of Therapeutic Stem Cells on TRAIL Resistant and Sensitive Medulloblastomas  

PubMed Central

Mesenchymal stem cells (MSC) are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential in medulloblastomas (MB) has not been explored to date. In this study, we engineered human MSC to express a potent and secretable variant of a tumor specific agent, tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL) and assessed the ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and -resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance correlates with the expression of its cognate death receptor (DR)5 and MSC-S-TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines. In TRAIL-resistant MB, we show upregulation of DR4/5 levels when pre-treated with MS-275 and a subsequent sensitization to MSC-S-TRAIL mediated apoptosis. Using intracranially implanted MB and MSC lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that MSC-S-TRAIL has significant anti-tumor effects in mice bearing TRAIL-sensitive and MS-275 pre-treated TRAIL-resistant MBs. To our knowledge, this is the first study that explores the use of human MSC as MB-targeting therapeutic-vehicles in vivo in TRAIL-sensitive and resistant tumors, and has implications for developing effective therapies for patients with medulloblastomas.

Bagci-Onder, Tugba; Anderegg, Maarten; Shah, Khalid

2012-01-01

338

Adult Stem Cells and Diseases of Aging  

PubMed Central

Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.

Boyette, Lisa B.; Tuan, Rocky S.

2014-01-01

339

Immunological characteristics of mesenchymal stem cells  

PubMed Central

Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

Machado, Cintia de Vasconcellos; Telles, Paloma Dias da Silva; Nascimento, Ivana Lucia Oliveira

2013-01-01

340

GPCRs in Stem Cell Function  

PubMed Central

Many tissues of the body cannot only repair themselves, but also self-renew, a property mainly due to stem cells and the various mechanisms that regulate their behavior. Stem cell biology is a relatively new field. While advances are slowly being realized, stem cells possess huge potential to ameliorate disease and counteract the aging process, causing its speculation as the next panacea. Amidst public pressure to advance rapidly to clinical trials, there is a need to understand the biology of stem cells and to support basic research programs. Without a proper comprehension of how cells and tissues are maintained during the adult life span, clinical trials are bound to fail. This review will cover the basic biology of stem cells, the various types of stem cells, their potential function, and the advantages and disadvantages to their use in medicine. We will next cover the role of G-protein coupled receptors in the regulation of stem cells and their potential in future clinical applications.

DOZE, VAN A.; PEREZ, DIANNE M.

2013-01-01

341

Emerging models and paradigms for stem cell ageing  

PubMed Central

Ageing is accompanied by a progressive decline in stem cell function, resulting in less effective tissue homeostasis and repair. Here we discuss emerging invertebrate models that provide insights into molecular pathways of age-related stem cell dysfunction in mammals, and we present various paradigms of how stem cell functionality changes with age, including impaired self-renewal and aberrant differentiation potential.

Jones, D. Leanne; Rando, Thomas A.

2012-01-01

342

PBS Online NewsHour: Adult Stem Cells  

NSDL National Science Digital Library

In-depth coverage of the potential health effects of adult stem cell therapies, together with instructional materials. Includes a lesson plan on the debate over using stem cells, Q-and-A with researchers, stories on stem cell use, and links to related PBS resources. Main story is available in streaming video and RealAudio as well as text.

343

Curcumin enhances the effectiveness of cisplatin by suppressing CD133+ cancer stem cells in laryngeal carcinoma treatment  

PubMed Central

Chemoresistance is one of the major barriers to chemotherapeutic treatment and it has been established that CD133+ cancer stem cells are responsible for drug resistance in laryngeal carcinoma. In the present study, curcumin and cisplatin were used as a combined treatment to induce the sensitivity of CD133+ cancer stem cells to chemotherapeutic agents and to enhance therapeutic effectiveness. The results revealed that in untreated and cisplatin-treated HEp-2 cell groups, the percentage of CD133+ cells was 4.50 and 6.89%, respectively. However, in the combined treatment group, the percentage of CD133+ cells was markedly reduced to 1.49%, indicating that curcumin may increase the sensitivity of CD133+ cells to cisplatin, leading to the suppression of chemoresistance in HEp-2 cells. Furthermore, the expression of ATP-binding cassette sub-family G member 2 (ABCG2), which is an important gene for chemoresistance, was demonstrated to be reduced in CD133+ cancer stem cells following combined treatment. These results suggest that the combined application of curcumin with chemotherapeutic drugs may be a reliable and effective approach for the treatment of laryngeal carcinoma.

ZHANG, HEJIA; YU, TIANYU; WEN, LIANJI; WANG, HUI; FEI, DAN; JIN, CHUNSHUN

2013-01-01

344

Accelerated and enhanced effect of CCR5-transduced bone marrow neural stem cells on autoimmune encephalomyelitis  

PubMed Central

The suppressive effect of neural stem cells (NSCs) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), has been reported. However, the migration of NSCs to inflammatory sites was relatively slow as was the onset of rather limited clinical benefit. Lack of, or low expression of particular chemokine receptors on NSCs could be an important factor underlying the slow migration of NSCs. To enhance the therapeutic effect of NSCs, in the present study we transduced bone marrow (BM)-derived NSCs with CCR5, a receptor for CCL3, CCL4, and CCL5, chemokines that are abundantly produced in CNS-inflamed foci of MS/EAE. After i.v. injection, CCR5-NSCs rapidly reached EAE foci in larger numbers, and more effectively suppressed CNS inflammatory infiltration, myelin damage, and clinical EAE than GFP-NSCs used as controls. CCR5-NSC-treated mice also exhibited augmented remyelination and neuron/oligodendrocyte repopulation compared to PBS- or GFP-NSC-treated mice. We inferred that the critical mechanism underlying enhanced effect of CCR5-transduced NSCs on EAE is the early migration of chemokine receptor-transduced NSCs into the inflamed foci. Such migration at an earlier stage of inflammation enables NSCs to exert more effective immunomodulation, to reduce the extent of early myelin/neuron damage by creating a less hostile environment for remyelinating cells, and possibly to participate in the remyelination/neural re-population process. These features of BM-derived transduced NSCs, combined with their easy availability (the subject’s own BM) and autologous properties, may lay the groundwork for an innovative approach to rapid and highly effective MS therapy.

Yang, Jingxian; Yan, Yaping; Ma, Cun-Gen; Kang, Tingguo; Zhang, Nan; Gran, Bruno; Xu, Hui; Li, Ke; Ciric, Bogoljub; Zangaladze, Andro; Curtis, Mark; Rostami, Abdolmohamad; Zhang, Guang-Xian

2013-01-01

345

Effects of minocycline on endogenous neural stem cells after experimental stroke.  

PubMed

Minocycline has been reported to reduce infarct size after focal cerebral ischemia, due to an attenuation of microglia activation and prevention of secondary damage from stroke-induced neuroinflammation. We here investigated the effects of minocycline on endogenous neural stem cells (NSCs) in vitro and in a rat stroke model. Primary cultures of fetal rat NSCs were exposed to minocycline to characterize its effects on cell survival and proliferation. To assess these effects in vivo, permanent cerebral ischemia was induced in adult rats, treated systemically with minocycline or placebo. Imaging 7 days after ischemia comprised (i) Magnetic Resonance Imaging (MRI), assessing the extent of infarcts, (ii) Positron Emission Tomography (PET) with [(11)C]PK11195, characterizing neuroinflammation, and (iii) PET with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT), detecting proliferating endogenous NSCs. Immunohistochemistry was used to verify ischemic damage and characterize cellular inflammatory and repair processes in more detail. In vitro, specific concentrations of minocycline significantly increased NSC numbers without increasing their proliferation, indicating a positive effect of minocycline on NSC survival. In vivo, endogenous NSC activation in the subventricular zone (SVZ) measured by [(18)F]FLT PET correlated well with infarct volumes. Similar to in vitro findings, minocycline led to a specific increase in endogenous NSC activity in both the SVZ as well as the hippocampus. [(11)C]PK11195 PET detected neuroinflammation in the infarct core as well as in peri-infarct regions, with both its extent and location independent of the infarct size. The data did not reveal an effect of minocycline on stroke-induced neuroinflammation. We show that multimodal PET imaging can be used to characterize and quantify complex cellular processes occurring after stroke, as well as their modulation by therapeutic agents. We found minocycline, previously implied in attenuating microglial activation, to have positive effects on endogenous NSC survival. These findings hold promise for the development of novel treatments in stroke therapy. PMID:22542871

Rueger, M A; Muesken, S; Walberer, M; Jantzen, S U; Schnakenburg, K; Backes, H; Graf, R; Neumaier, B; Hoehn, M; Fink, G R; Schroeter, M

2012-07-26

346

Issues in-depth: Setting FIRES to stem cell research  

NSDL National Science Digital Library

Stem cell research is constantly under "fire" in the media today. Use this effective strategy to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. Using the FIRES (Facts, Incidents, Reasons, Examples, and Statistics) strategy, students evaluate stem cell information from multiple sources and gain a deeper understanding of this sensitive topic.

Miller, Roxanne G.

2005-07-01

347

Reprogramming sertoli cells into pluripotent stem cells.  

PubMed

Abstract Induced pluripotent stem cells (iPSCs) have potential applications in the restoration of fertility, regenerative medicine, and animal biotechnology. In this study, we present the induction of iPSCs from mouse Sertoli cells (SCs) by introducing four factors-Oct4, Sox2, Klf4, and c-Myc. As early as day 3 after induction, expression of these factors was detected and typical embryonic stem-like cells began to form. On day 18, these exogenous genes were silenced and colonies were selected according to morphological characteristics. The iPSCs induced from SCs, termed SCiPSCs, strongly expressed pluripotent markers, showed a normal karyotype, and had proliferation and differentiation characteristics similar to those of embryonic stem cells (ESCs), both in vitro and in vivo. Furthermore, exposure of SCiPSCs to nitric oxide (NO) allowed them to maintain pluripotency through the activation of the pluripotent genes Oct4 and Sox2 and upregulation of Nanog expression. Moreover, NO prevented SCiPSCs from undergoing apoptosis by activating the antiapoptotic genes Bcl2 and Bcl2lll, downregulating the proapoptotic genes Bak1 and Casp7, and blocking the activation of the proapoptotic gene Bac. These effects were reversed by exposure to l-NG-monomethylarginine (l-NMMA), a NO inhibitor. These data demonstrate that iPSCs can be generated from SCs and that the self-renewal and pluripotency of SCiPS cells can be maintained in the presence of NO. PMID:24802333

Sun, Hongyan; Zhang, Guomin; Dong, Fulu; Wang, Feng; Cao, Wenguang

2014-06-01

348

Stem Cell Therapy for Autism  

PubMed Central

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism.

Ichim, Thomas E; Solano, Fabio; Glenn, Eduardo; Morales, Frank; Smith, Leonard; Zabrecky, George; Riordan, Neil H

2007-01-01

349

Encapsulated Glucagon-Like Peptide-1-Producing Mesenchymal Stem Cells Have a Beneficial Effect on Failing Pig Hearts  

PubMed Central

Stem cell therapy is an exciting and emerging treatment option to promote post-myocardial infarction (post-MI) healing; however, cell retention and efficacy in the heart remain problematic. Glucagon-like peptide-1 (GLP-1) is an incretin hormone with cardioprotective properties but a short half-life in vivo. The effects of prolonged GLP-1 delivery from stromal cells post-MI were evaluated in a porcine model. Human mesenchymal stem cells immortalized and engineered to produce a GLP-1 fusion protein were encapsulated in alginate (bead-GLP-1 MSC) and delivered to coronary artery branches. Control groups were cell-free beads and beads containing unmodified MSCs (bead-MSC), n = 4–5 per group. Echocardiography confirmed left ventricular (LV) dysfunction at time of delivery in all groups. Four weeks after intervention, only the bead-GLP-1 MSC group demonstrated LV function improvement toward baseline and showed decreased infarction area compared with controls. Histological analysis showed reduced inflammation and a trend toward reduced apoptosis in the infarct zone. Increased collagen but fewer myofibroblasts were observed in infarcts of the bead-GLP-1 MSC and bead-MSC groups, and significantly more vessels per mm2 were noted in the infarct of the bead-GLP-1 MSC group. No differences were observed in myocyte cross-sectional area between groups. Post-MI delivery of GLP-1 encapsulated genetically modified MSCs provided a prolonged supply of GLP-1 and paracrine stem cell factors, which improved LV function and reduced epicardial infarct size. This was associated with increased angiogenesis and an altered remodeling response. Combined benefits of paracrine stem cell factors and GLP-1 were superior to those of stem cells alone. These results suggest that encapsulated genetically modified MSCs would be beneficial for recovery following MI.

Wright, Elizabeth J.; Farrell, Kelly A.; Malik, Nadim; Kassem, Moustapha; Lewis, Andrew L.; Wallrapp, Christine

2012-01-01

350

The effect of temperature on the viability of human mesenchymal stem cells  

PubMed Central

Introduction Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs. Methods The viability of human MSCs was measured after incubating them at temperatures of 38°C, 48°C and 58°C; durations 45 seconds, 80 seconds and 150 seconds. A control group was kept at 37°C and 5% carbon dioxide for the duration of the investigation (7 days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlue™ assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnett’s test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlue™) and cell viability (Trypan Blue). Results Results showed that cell metabolism was not severely affected up to 48°C/150 seconds, while cells in the 58°C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48°C/150 seconds were compared with the control group. Conclusions The study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48°C for 150 seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations.

2013-01-01

351

The effect of actin disrupting agents on contact guidance of human embryonic stem cells  

Microsoft Academic Search

Mammalian cells respond to their substrates by complex changes in gene expression profiles, morphology, proliferation and migration. We report that substrate nanotopography alters morpohology and proliferation of human embryonic stem cells (hESCs). Fibronectin-coated poly(di-methyl siloxane) substrates with line-grating (600nm ridges with 600nm spacing and 600±150nm feature height) induced hESC alignment and elongation, mediated the organization of cytoskeletal components including actin,

Sharon Gerecht; Christopher J. Bettinger; Zhitong Zhang; Jeffrey T. Borenstein; Gordana Vunjak-Novakovic; Robert Langer

2007-01-01

352

Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells  

PubMed Central

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; 25 µg/ml) and methotrexate (MTX; 50 µg/ml), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptasepolymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.

Yi, Hee; Cho, Hee-Jung; Cho, Soo-Min; Jo, Kyul; Park, Jin-A; Lee, Soo-Han; Chang, Byung-Joon; Kim, Jin-Suk

2012-01-01

353

Effect of anti-CD52 antibody alemtuzumab on ex-vivo culture of umbilical cord blood stem cells  

Microsoft Academic Search

BACKGROUND: Excessive maturation of hematopoietic cells leads to a reduction of long-term proliferative capability during cord blood (CB) expansion. In this study, we report the effects of anit-CD52 (Alemtuzumab, Campath) on both short- and long-term ex vivo expansion of CB hematopoietic stem cells (HSC) by evaluating the potential role of Alemtuzumab in preserving the repopulating capability in CB HSC and

Che K Lim; Li Sun; Qi Feng; Ping Law; Wei T Chua; Shy N Lim; William YK Hwang

2008-01-01

354

Stem cell therapy for the spinal cord.  

PubMed

ABSTRACT: Injury and disease of the spinal cord are generally met with a poor prognosis. This poor prognosis is due not only to the characteristics of the diseases but also to our poor ability to deliver therapeutics to the spinal cord. The spinal cord is extremely sensitive to direct manipulation, and delivery of therapeutics has proven a challenge for both scientists and physicians. Recent advances in stem cell technologies have opened up a new avenue for the treatment of spinal cord disease and injury. Stem cells have proven beneficial in rodent models of spinal cord disease and injury. In these animal models, stem cells have been shown to produce their effect by the dual action of cell replacement and the trophic support of the factors secreted by these cells. In this review we look at the main clinical trials involving stem cell transplant into the spinal cord, focusing on motor neuron diseases and spinal cord injury. We will also discuss the major hurdles in optimizing stem cell delivery methods into the spinal cord. We shall examine current techniques such as functional magnetic resonance imaging guidance and cell labeling and will look at the current research striving to improve these techniques. With all caveats and future research taken into account, this is a very exciting time for stem cell transplant into the spinal cord. We are only beginning to realize the huge potential of stem cells in a central nervous system setting to provide cell replacement and trophic support. Many more trials will need to be undertaken before we can fully exploit the attributes of stem cells. PMID:22776143

Donnelly, Eleanor M; Lamanna, Jason; Boulis, Nicholas M

2012-07-01

355

Stem cell therapy for the spinal cord  

PubMed Central

Injury and disease of the spinal cord are generally met with a poor prognosis. This poor prognosis is due not only to the characteristics of the diseases but also to our poor ability to deliver therapeutics to the spinal cord. The spinal cord is extremely sensitive to direct manipulation, and delivery of therapeutics has proven a challenge for both scientists and physicians. Recent advances in stem cell technologies have opened up a new avenue for the treatment of spinal cord disease and injury. Stem cells have proven beneficial in rodent models of spinal cord disease and injury. In these animal models, stem cells have been shown to produce their effect by the dual action of cell replacement and the trophic support of the factors secreted by these cells. In this review we look at the main clinical trials involving stem cell transplant into the spinal cord, focusing on motor neuron diseases and spinal cord injury. We will also discuss the major hurdles in optimizing stem cell delivery methods into the spinal cord. We shall examine current techniques such as functional magnetic resonance imaging guidance and cell labeling and will look at the current research striving to improve these techniques. With all caveats and future research taken into account, this is a very exciting time for stem cell transplant into the spinal cord. We are only beginning to realize the huge potential of stem cells in a central nervous system setting to provide cell replacement and trophic support. Many more trials will need to be undertaken before we can fully exploit the attributes of stem cells.

2012-01-01

356

Microbioreactors for Stem Cell Research  

NASA Astrophysics Data System (ADS)

During tissue development and regeneration, stem cells respond to the entire milieu of their environment, through dynamic interactions with the surrounding cells, extracellular matrix, and cascades of molecular and physical regulatory factors. A new generation of culture systems is emerging to offer some of the biological fidelity of a whole organism within highly controllable in vitro settings and provide the cultured cells with the combinations of factors they normally encounter in vivo. There is a growing notion that such "biomimetic" systems are essential for unlocking the full potential of stem cells - for tissue regeneration as well as biological research. In this chapter, we discuss the biological principles for designing biologically inspired culture systems for stem cell research and focus on the control of stem cell microenvironment through surface patterning, microfluidics, and electrical stimulation.

Freytes, Donald O.; Vunjak-Novakovic, Gordana

357

Effect of nano-structured bioceramic surface on osteogenic differentiation of adipose derived stem cells.  

PubMed

Tissue engineering strategies to construct vascularized bone grafts potentially revolutionize the treatment of massive bone loss. The surface topography of the grafts plays critical roles on bone regeneration, while adipose derived stem cells (ASCs) are known for their capability to promote osteogenesis and angiogenesis when applied to bone defects. In the present study, the effects of hydroxyapatite (HAp) bioceramic scaffolds with nanosheet, nanorod, and micro-nano-hybrid (the hybrid of nanorod and microrod) surface topographies on attachment, proliferation and osteogenic differentiation, as well as the expression of angiogenic factors of rat ASCs were systematically investigated. The results showed that the HAp bioceramic scaffolds with the micro-/nano-topography surfaces significantly enhanced cell attachment and viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteogenic markers and angiogenic factors of ASCs. More importantly, the biomimetic feature of the hierarchical micro-nano-hybrid surface topography showed the highest stimulatory effect. The activation in Akt signaling pathway was observed in ASCs cultured on HAp bioceramics with nanorod, and micro-nano-hybrid surface topographies. Moreover, these induction effects could be repressed by Akt signaling pathway inhibitor LY294002. Finally, the in vivo bone regeneration results of rat critical-sized calvarial defect models confirmed that the combination of the micro-nano-hybrid surface and ASCs could significantly enhance both osteogenesis and angiogenesis as compared with the control HAp bioceramic scaffold with traditional smooth surface. Our results suggest that HAp bioceramic scaffolds with micro-nano-hybrid surface can act as cell carrier for ASCs, and consequently combine with ASCs to construct vascularized tissue-engineered bone. PMID:25002263

Xia, Lunguo; Lin, Kaili; Jiang, Xinquan; Fang, Bing; Xu, Yuanjin; Liu, Jiaqiang; Zeng, Deliang; Zhang, Maolin; Zhang, Xiuli; Chang, Jiang; Zhang, Zhiyuan

2014-10-01

358

Therapeutic effect of bortezomib for primary plasma cell leukemia followed by auto/allo stem cell transplantation  

PubMed Central

Plasma cell leukemia (PCL) is a rare disease that represents approximately 4% of plasma cell malignant disorders. PCL consists of two variants: primary PCL presents in patients with no previous history of multiple myeloma, while secondary PCL consists of a leukemic transformation in a previously recognized multiple myeloma. Primary PCL is an extremely resistant, rapidly progressive, fatal disease, with a median overall survival of 6.8 months. There is no standard therapeutic strategy, because no treatment option has been prospectively evaluated. We describe a successful case of newly diagnosed primary PCL, treated with a regimen that included bortezomib, followed by auto stem cell transplantation and nonmyeloablative allogeneic stem cell transplantation. Our patient has maintained remission status for over 12 months since undergoing the allogeneic stem cell transplantation. This strategy is promising for PCL, which, though an extremely resistant disease, may become curable.

Ozasa, Ryotaro; Hotta, Masaaki; Yoshimura, Hideaki; Nakanishi, Takahisa; Tamaki, Takeshi; Fujita, Shinya; Nakamichi, Naoto; Miyaji, Michihiko; Ishii, Kazuyoshi; Ito, Tomoki; Nomura, Shosaku

2012-01-01

359

Polyester ?-assay chip for stem cell studies  

PubMed Central

The application of microfluidic technologies to stem cell research is of great interest to biologists and bioengineers. This is chiefly due to the intricate ability to control the cellular environment, the reduction of reagent volume, experimentation time and cost, and the high-throughput screening capabilities of microscale devices. Despite this importance, a simple-to-use microfluidic platform for studying the effects of growth factors on stem cell differentiation has not yet emerged. With this consideration, we have designed and characterized a microfluidic device that is easy to fabricate and operate, yet contains several functional elements. Our device is a simple polyester-based microfluidic chip capable of simultaneously screening multiple independent stem cell culture conditions. Generated by laser ablation and stacking of multiple layers of polyester film, this device integrates a 10?×?10 microwell array for cell culture with a continuous perfusion system and a non-linear concentration gradient generator. We performed numerical calculations to predict the gradient formation and calculate the shear stress acting on the cells inside the device. The device operation was validated by culturing murine embryonic stem cells inside the microwells for 5 days. Furthermore, we showed the ability to maintain the pluripotency of stem cell aggregates in response to concentrations of leukemia inhibitory factor ranging from 0 to ?1000 U/ml. Given its simplicity, fast manufacturing method, scalability, and the cell-compatible nature of the device, it may be a useful platform for long-term stem cell culture and studies.

Piraino, Francesco; Selimovic, Seila; Adamo, Marco; Pero, Alessandro; Manoucheri, Sam; Bok Kim, Sang; Demarchi, Danilo; Khademhosseini, Ali

2012-01-01

360

Polyester ?-assay chip for stem cell studies.  

PubMed

The application of microfluidic technologies to stem cell research is of great interest to biologists and bioengineers. This is chiefly due to the intricate ability to control the cellular environment, the reduction of reagent volume, experimentation time and cost, and the high-throughput screening capabilities of microscale devices. Despite this importance, a simple-to-use microfluidic platform for studying the effects of growth factors on stem cell differentiation has not yet emerged. With this consideration, we have designed and characterized a microfluidic device that is easy to fabricate and operate, yet contains several functional elements. Our device is a simple polyester-based microfluidic chip capable of simultaneously screening multiple independent stem cell culture conditions. Generated by laser ablation and stacking of multiple layers of polyester film, this device integrates a 10?×?10 microwell array for cell culture with a continuous perfusion system and a non-linear concentration gradient generator. We performed numerical calculations to predict the gradient formation and calculate the shear stress acting on the cells inside the device. The device operation was validated by culturing murine embryonic stem cells inside the microwells for 5 days. Furthermore, we showed the ability to maintain the pluripotency of stem cell aggregates in response to concentrations of leukemia inhibitory factor ranging from 0 to ?1000 U/ml. Given its simplicity, fast manufacturing method, scalability, and the cell-compatible nature of the device, it may be a useful platform for long-term stem cell culture and studies. PMID:24278097

Piraino, Francesco; Selimovi?, Seila; Adamo, Marco; Pero, Alessandro; Manoucheri, Sam; Bok Kim, Sang; Demarchi, Danilo; Khademhosseini, Ali

2012-01-01

361

Cell rheology: Stressed-out stem cells  

NASA Astrophysics Data System (ADS)

Experiments have shown that the physical characteristics of the matrix surrounding a stem cell can affect its behaviour. This picture gets further complicated by studies of stem cells and their differentiated counterparts that show that the cells' own softness also has a clear role in how they respond to stress.

Holle, Andrew W.; Engler, Adam J.

2010-01-01

362

Dose Dependent Side Effect of Superparamagnetic Iron Oxide Nanoparticle Labeling on Cell Motility in Two Fetal Stem Cell Populations  

PubMed Central

Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies.

Diana, Valentina; Bossolasco, Patrizia; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

2013-01-01

363

Sources of Stem Cells for Transplant  

MedlinePLUS

... Donor matching for allogeneic transplant Sources of stem cells for transplant There are 3 possible sources of ... blood transplants are being actively studied. Which stem cell source is best? All 3 sources of stem ...

364

Cancer Stem Cells and Radiation  

Microsoft Academic Search

Cancer stem cells have recently been proposed to play a significant role in the initiation and propagation of tumor cells.\\u000a They display indefinite self-renewal capacity and multilineage potential as well as an excessive proliferation capacity. Cancer\\u000a stem cells are quiescent with low mitotic frequencies. They seem to be relatively radioresistant and have been demonstrated\\u000a to increase in relative amount following

David Eriksson; Katrine Riklund; Lennart Johansson; Torgny Stigbrand

365

Stem Cells in the Lung  

PubMed Central

The lung is composed of two major anatomically distinct regions—the conducting airways and gas-exchanging airspaces. From a cell biology standpoint, the conducting airways can be further divided into two major compartments, the tracheobronchial and bronchiolar airways, while the alveolar regions of the lung make up the gas-exchanging airspaces. Each of these regions consists of distinct epithelial cell types with unique cellular physiologies and stem cell compartments. This chapter focuses on model systems with which to study stem cells in the adult tracheobronchial airways, also referred to as the proximal airway of the lung. Important in such models is an appreciation for the diversity of stem cell niches in the conducting airways that provide localized environmental signals to both maintain and mobilize stem cells in the setting of airway injury and normal cellular turnover. Because cellular turnover in airways is relatively slow, methods for analysis of stem cells in vivo have required prior injury to the lung. In contrast, ex vivo and in vitro models for analysis of airway stem cells have used genetic markers to track lineage relationships together with reconstitution systems that mimic airway biology. Over the past decades, several widely acceptable methods have been developed and used in the characterization of adult airway stem/ progenitor cells. These include localization of label-retaining cells (LRCs), retroviral tagging of epithelial cells seeded into xenografts, air–liquid interface cultures to track clonal proliferative potential, and multiple transgenic mouse models. This chapter reviews the biologic context and use of these models while providing detailed methods for several of the more broadly useful models for studying adult airway stem/progenitor cell types.

Liu, Xiaoming; Driskell, Ryan R.; Engelhardt, John F.

2007-01-01

366

Effects of substrate mechanics on contractility of cardiomyocytes generated from human pluripotent stem cells.  

PubMed

Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4-99.7?kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for ?-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies. PMID:22649451

Hazeltine, Laurie B; Simmons, Chelsey S; Salick, Max R; Lian, Xiaojun; Badur, Mehmet G; Han, Wenqing; Delgado, Stephanie M; Wakatsuki, Tetsuro; Crone, Wendy C; Pruitt, Beth L; Palecek, Sean P

2012-01-01

367

Effects of valproic acid on gene expression during human embryonic stem cell differentiation into neurons.  

PubMed

The widely used antiepileptic drug valproic acid (VPA) is known to exhibit teratogenicity in the form of a failure of the neural tube in humans. Embryonic stem cells (ESCs) are reported to be a promising cell source for evaluating chemical teratogenicity, because they are capable of reproducing embryonic developmental model and enable reduction in the number of experimental animals used. We previously investigated 22 genes for which expressions are altered by teratogens, specifically focusing on neural differentiation of mouse ESCs. In the present study, expressions of the investigated genes were evaluated by quantitative real-time PCR and compared during differentiation of human ESCs into neurons with or without VPA. Under the conditions, almost all gene expressions significantly changed in VPA-containing culture. Specifically, in neural development-related genes such as DCX, ARX, MAP2, and NNAT, more than 2-fold expression was observed. The findings suggest that the genes focused on in this study may help to elucidate the teratogenic effects of VPA and might be a useful tool to analyze embryotoxic potential of chemicals in humans. PMID:24849673

Ehashi, Tomo; Suzuki, Noriyuki; Ando, Satoshi; Sumida, Kayo; Saito, Koichi

2014-01-01

368

Xanthones with antiproliferative effects on prostate cancer cells from the stem bark of Garcinia xanthochymus.  

PubMed

Investigations of the constituents of the stem barks of Garcinia xanthochymus have yielded two new compounds, garcinenones X (1) and Y (2), along with five known xanthones, 1,4,5,6-tetrahydroxy-7-(3-methylbut-2-enyl)xanthone (3), 1,4,6-trihydroxy-5-methoxy-7-(3-methylbut-2-enyl)xanthone (4), 1,4,5,6-tetrahydroxy-7,8-di(3-methylbut-2-enyl)xanthone (5), 1,3,5,6-tetrahydroxy-4,7,8-tri(3-methylbut-2-enyl)xanthone (6), and 1,5,6-trihydroxy-7,8-di(3-methylbut-2-enyl)-6',6'dimethylpyrano(2',3':3,4)xanthone (7). The structures of the compounds were determined by spectroscopic methods. The cell growth inhibitory activity of the isolated compounds against the PC-3 cell line was measured. Among them, compounds 2, 3, 5, and 6 exhibited significant inhibitory effects with IG50 values of 14.3, 15.5, 11.1, and 6.8 microM, respectively. PMID:22428244

Ji, Feng; Lia, Zhanlin; Liu, Gaofeng; Niu, Shengli; Zhao, Nan; Liu, Xiaoqiu; Hua, Huiming

2012-01-01

369

Effect of Cardiac Stem Cells in Patients with Ischemic Cardiomyopathy: Initial Results of the SCIPIO Trial  

PubMed Central

Summary Background C-kit+ lineage? cardiac stem cells (CSCs) improve postinfarction left ventricular (LV) dysfunction in animals; however, their efficacy in humans is unknown. Methods In February 2009, we began SCIPIO (Stem Cell Infusion in Patients with Ischemic CardiOmyopathy), a Phase I, randomized, open-label trial of CSCs in patients with postinfarction LV dysfunction (ejection fraction [EF] ? 40%) who underwent coronary bypass surgery. Autologous CSCs were isolated from the right atrial appendage and re-infused intracoronarily 4 ± 1 months after surgery; controls received no treatment. In Stage A, 9 treated and 4 control patients were consecutively enrolled to assess the feasibility and short-term safety of CSCs. Then, in Stage B, patients were randomized to the treated or control arm in a 2:3 ratio using a block randomization scheme and a block size of five. Primary (safety) and secondary (efficacy) endpoints were assessed at serial times after enrollment. Findings Autologous CSCs were successfully isolated and expanded in 80 out of 81 patients. In 16 treated patients, no CSC-related adverse effects have been observed. LVEF (3D echocardiography) increased from 30.3 ± 1.9% before CSC infusion to 38.5 ± 2.8% at 4 months after infusion, (P=0.001, n=14). This was associated with an improvement in regional wall motion score index (echocardiography) (1.91 ± 0.09 vs. 1.73 ± 0.09, P=0.005), NYHA functional class (2.19 ± 0.16 vs. 1.63 ± 0.16, P=0.003), and quality of life (MLHFQ score, 46.44 ± 5.22 vs. 26.69 ± 4.92, P<0.0001). In contrast, in 7 control patients, none of these variables changed appreciably during the corresponding time-interval. Importantly, the salubrious effects of CSCs were even more pronounced at 1 year (e.g., LVEF increased by 12.3 ± 2.1% vs. pre-CSCs, P=0.0007, n=8), suggesting that CSCs continue to improve LV function beyond the first 4 months. In the 7 treated patients in whom cardiac magnetic resonance (cMR) imaging could be performed, infarct size decreased by 7.8 ± 1.7 g (23.8%) at 4 months (P=0.004) and 9.8 ± 3.5 g (30.3%) at 1 year (P=0.04). Interpretation These initial results in humans are very encouraging, and suggest that infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure.

Bolli, Roberto; Chugh, Atul R.; D'Amario, Domenico; Loughran, John H.; Stoddard, Marcus F.; Ikram, Sohail; Beache, Garth M.; Wagner, Stephen G.; Leri, Annarosa; Hosoda, Toru; Elmore, Julius B.; Goihberg, Polina; Cappetta, Donato; Solankhi, Naresh K.; Fahsah, Ibrahim; Rokosh, D. Gregg; Slaughter, Mark S.; Kajstura, Jan; Anversa, Piero

2011-01-01

370

Effect of Labeling with Iron Oxide Particles or Nanodiamonds on the Functionality of Adipose-Derived Mesenchymal Stem Cells  

PubMed Central

Stem cells are increasingly the focus of translational research as well as having emerging roles in human cellular therapy. To support these uses there is a need for improved methods for in vivo cell localization and tracking. In this study, we examined the effects of cell labeling on the in vitro functionality of human adipose-derived mesenchymal stem cells. Our results provide a basis for future in vivo studies investigating implanted cell fate and longevity. In particular, we investigated the effects of two different particles: micron-sized (?0.9 µm) fluorescently labeled (Dragon Green) superparamagnetic iron oxide particles (M-SPIO particles); and, carboxyl