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  1. Cryptococcal meningitis post autologous stem cell transplantation.

    PubMed

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.

  2. [Post-hematopietic stem cell transplant complications].

    PubMed

    de Berranger, Eva; Jubert, Charlotte; Michel, Gérard

    2015-01-01

    Under the long-term monitoring of patients treated in childhood or adolescence for cancer, we present in this article the long-term monitoring and therefore possible effects of patients who underwent allergenic hematopoietic stem cell transplantation. This article is based on a collaborative effort organized by the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which took place during the 4th day of allograft harmonization practices. Patients affected are children and young adults (0-25 years). We defined the monitoring effects beyond 1 year post-transplant. Our recommendations are based on a literature review, in line with the Leucémie Enfant Adulte (LEA) study cohort of long-term monitoring of patients treated for hematological malignancies in childhood, grafted or not. It became important to determine the nature of problems, their risk factors, frequency and monitoring necessary to implement for their detection. We will not address the therapeutic management of sequelae.

  3. Post-hematopoietic stem cell transplantion immune-mediated cytopenias.

    PubMed

    Tsirigotis, Panagiotis D; Resnick, Igor B; Or, Reuven; Elad, Sharon; Zilberman, Irina; Yoffe, Luba; Levovic, Alexander; Miron, Svetlana; Gesundheit, Benjamin; Slavin, Shimon; Shapira, Michael-Yechiel

    2009-01-01

    Immune-mediated cytopenias after allogeneic stem cell transplantation can be categorized as either alloimmune when host or donor immunity reacts against donor or host elements, respectively, or autoimmune when donor immunity reacts against donor hematopoietic tissue, owing to poorly understood mechanisms that result in severe impairment of central and peripheral tolerance. Immune cytopenias are manifested as monolineage or more rarely as bilineage cytopenias, and are usually mediated through humoral immune mechanisms. On the contrary, immune-mediated pancytopenia is a rare event with only few cases reported in the literature. The exact pathogenesis of immune pancytopenia is not well known although it is possible that cellular immunity may play a significant role. The importance of these syndromes lies in the fact that they can cause severe morbidity and mortality. Differential diagnosis from other causes of post-transplant pancytopenia is of extreme value because these disorders can respond to various treatment modalities.

  4. Stem Cells

    MedlinePlus

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

  5. Human Stem Cells Can Differentiate in Post-implantation Mouse Embryos.

    PubMed

    Tam, Patrick P L

    2016-01-07

    The potency of human pluripotent stem cells (hPSCs) to differentiate into germ layer derivatives is conventionally assessed by teratoma induction and in vitro differentiation. In this issue of Cell Stem Cell, Mascetti and Pedersen (2016) demonstrate that the human-mouse post-implantation chimera offers an efficient avenue to test the germ layer differentiation potential of hPSCs in mouse embryos ex vivo.

  6. Prostaglandin E₂ promotes post-infarction cardiomyocyte replenishment by endogenous stem cells.

    PubMed

    Hsueh, Ying-Chang; Wu, Jasmine M F; Yu, Chun-Keung; Wu, Kenneth K; Hsieh, Patrick C H

    2014-04-01

    Although self-renewal ability of adult mammalian heart has been reported, few pharmacological treatments are known to promote cardiomyocyte regeneration after injury. In this study, we demonstrate that the critical period of stem/progenitor cell-mediated cardiomyocyte replenishment is initiated within 7 days and saturates on day 10 post-infarction. Moreover, blocking the inflammatory reaction with COX-2 inhibitors may also reduce the capability of endogenous stem/progenitor cells to repopulate lost cells. Injection of the COX-2 product PGE2 enhances cardiomyocyte replenishment in young mice and recovers cell renewal through attenuating TGF-β1 signaling in aged mice. Further analyses suggest that cardiac stem cells are PGE2-responsive and that PGE2 may regulate stem cell activity directly through the EP2 receptor or indirectly by modulating its micro-environment in vivo. Our findings provide evidence that PGE2 holds great potential for cardiac regeneration.

  7. Post-transcriptional regulation of gene expression in neural stem cells.

    PubMed

    Kim, Do-Yeon

    2016-06-01

    Expression of each gene can be controlled at several steps during the flow of genetic information from DNA to protein. Tight regulation of gene expression is especially important for stem cells because of their greater ripple effects, compared with terminally differentiated cells. Dysregulation of gene expression arising in stem cells can be perpetuated within the stem cell pool via self-renewal throughout life. In addition, transcript profiles within stem cells can determine the selective advantage or disadvantage of each cell, leading to changes in cell fate, such as a tendency for proliferation, death, and differentiation. The identification of neural stem/progenitor cells (NSPCs) and greater understanding of their cellular physiology have raised the possibility of using NSPCs to replace damaged or injured neurons. However, an accurate grasp of gene expression control must take precedence in order to use NSPCs in therapies for neurological diseases. Recently, accumulating evidence has demonstrated the importance of post-transcriptional regulation in NSPC fate decisions. In this review, we will summarize and discuss the recent findings on key mRNA modulators and their vital roles in NSPC homeostasis. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Exclusive multipotency and preferential asymmetric divisions in post-embryonic neural stem cells of the fish retina.

    PubMed

    Centanin, Lázaro; Ander, Janina-J; Hoeckendorf, Burkhard; Lust, Katharina; Kellner, Tanja; Kraemer, Isabel; Urbany, Cedric; Hasel, Eva; Harris, William A; Simons, Benjamin D; Wittbrodt, Joachim

    2014-09-01

    The potency of post-embryonic stem cells can only be addressed in the living organism, by labeling single cells after embryonic development and following their descendants. Recently, transplantation experiments involving permanently labeled cells revealed multipotent neural stem cells (NSCs) of embryonic origin in the medaka retina. To analyze whether NSC potency is affected by developmental progression, as reported for the mammalian brain, we developed an inducible toolkit for clonal labeling and non-invasive fate tracking. We used this toolkit to address post-embryonic stem cells in different tissues and to functionally differentiate transient progenitor cells from permanent, bona fide stem cells in the retina. Using temporally controlled clonal induction, we showed that post-embryonic retinal NSCs are exclusively multipotent and give rise to the complete spectrum of cell types in the neural retina. Intriguingly, and in contrast to any other vertebrate stem cell system described so far, long-term analysis of clones indicates a preferential mode of asymmetric cell division. Moreover, following the behavior of clones before and after external stimuli, such as injuries, shows that NSCs in the retina maintained the preference for asymmetric cell division during regenerative responses. We present a comprehensive analysis of individual post-embryonic NSCs in their physiological environment and establish the teleost retina as an ideal model for studying adult stem cell biology at single cell resolution.

  9. Role of HRCT Chest in Post Stem Cell Transplant Recipients Suspected of Pulmonary Complications

    PubMed Central

    Kumar, R Ravi; Sharma, Ajay; Pannu, S K

    2016-01-01

    Introduction Stem cell transplantation is today’s procedure of choice for management of various hematopoietic malignant and severe immunogenic disorders. High Resolution Computed Tomography (HRCT) is a common technique for the diagnosis of pulmonary complications in stem cell transplant recipients. There are a large number of complications which can complicate the post-transplant period. Aim To study the role of HRCT chest in stem cell transplant patients developing pulmonary complications, detect any evidence of infection, detect clinical signs of lung infections, Graft versus Host Disease (GvHD) or other regimen related toxicities outlined earlier, detect any evidence of GvHD and correlate these clinical signs with radiological changes in the lungs. Materials and Methods The study was a prospective study of 52 participants with indication of stem cell transplantation. The study included recipients of HSCT transplant and the exclusion criteria was patients who failed for engraftment and having an associated history of pulmonary embolism. Patients were screened for pre-transplant chemotherapy, clinical examination, laboratory investigations including blood and biochemical examinations, imaging by ultrasound, chest radiography, baseline HRCT and a follow-up for post-transplant infections and complications with 16 slice Siemens CT scan. Statistical analysis was done using Pearson’s chi-squared test. Results Four patients among the total 56 were excluded due to non-engraftment. The most common associated findings in decreasing order are (these patients died): consolidation, pancytopenia and gastrointestinal tract symptoms with VOD (Veno-Occlusive Disease). These findings were seen on HRCT as consolidation, cavities, ground glass opacities, fibrotic changes, bronchiectatic changes and tree in bud appearance. Conclusion The study highlights the significant positive findings on the HRCT which were missed on routine chest radiograph and can be used for early diagnoses

  10. Haploidentical Hematopoietic Stem Cell Transplantation as Platform for Post-transplant Cellular Therapy

    PubMed Central

    Kongtim, Piyanuch; Lee, Dean A.; Cooper, Laurence J. N.; Kebriaei, Partow; Champlin, Richard E.; Ciurea, Stefan O.

    2016-01-01

    Haploidentical transplantation can extend the opportunity for transplantation to almost all patients who lack an HLA-matched donor. Advances in the field of haploidentical transplantation have led to a marked decrease in treatment-related mortality, allowing investigators to focus on developing rationale pre- and peri-remission therapies aimed at preventing disease relapse post-transplant. Due to widespread availability, low treatment-related mortality and cost, haploidentical donors may become the preferred “alternative” donors for allogeneic hematopoietic stem cell transplantation. One of the major advantages of using a related donor is the possibility to collect or generate additional cellular products from the same immediate available donor, which will not be rejected. Infusion of these cells in the peri-transplant period, derived from the same immune system, is opening the possibility to markedly enhance the anti-tumor effects of the graft and hasten immunologic reconstitution post-transplant. PMID:26172479

  11. Stem cells.

    PubMed

    Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

    2010-10-01

    Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.

  12. Types of Stem Cells

    MedlinePlus

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  13. Role of Nanog in the maintenance of marrow stromal stem cells during post natal bone regeneration

    SciTech Connect

    Bais, Manish V.; Shabin, Zabrina M.; Young, Megan; Einhorn, Thomas A.; Kotton, Darrell N.; Gerstnefeld, Louis C.

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Nanog is related to marrow stromal stem cell maintenance. Black-Right-Pointing-Pointer Increasing Nanog expression is seen during post natal surgical bone repair. Black-Right-Pointing-Pointer Nanog knockdown decreases post surgical bone regeneration. -- Abstract: Post natal bone repair elicits a regenerative mechanism that restores the injured tissue to its pre-injury cellular composition and structure and is believed to recapitulate the embryological processes of bone formation. Prior studies showed that Nanog, a central epigenetic regulator associated with the maintenance of embryonic stem cells (ESC) was transiently expressed during fracture healing, Bais et al. . In this study, we show that murine bone marrow stromal cells (MSCs) before they are induced to undergo osteogenic differentiation express {approx}50 Multiplication-Sign the background levels of Nanog seen in murine embryonic fibroblasts (MEFs) and the W20-17 murine marrow stromal cell line stably expresses Nanog at {approx}80 Multiplication-Sign the MEF levels. Nanog expression in this cell line was inhibited by BMP7 treatment and Nanog lentivrial shRNA knockdown induced the expression of the terminal osteogenic gene osteocalcin. Lentivrial shRNA knockdown or lentiviral overexpression of Nanog in bone MSCs had inverse effects on proliferation, with knockdown decreasing and overexpression increasing MSC cell proliferation. Surgical marrow ablation of mouse tibia by medullary reaming led to a {approx}3-fold increase in Nanog that preceded osteogenic differentiation during intramembranous bone formation. Lentiviral shRNA knockdown of Nanog after surgical ablation led to an initial overexpression of osteogenic gene expression with no initial effect on bone formation but during subsequent remodeling of the newly formed bone a {approx}50% decrease was seen in the expression of terminal osteogenic gene expression and a {approx}50% loss in trabecular bone mass. This

  14. Transcriptional and post-transcriptional regulation of Drosophila germline stem cells and their differentiating progeny.

    PubMed

    White-Cooper, Helen; Caporilli, Simona

    2013-01-01

    In this chapter we will concentrate on the transcriptional and translational regulations that govern the development and differentiation of male germline cells. Our focus will be on the processes that occur during differentiation, that distinguish the differentiating population of cells from their stem cell parents. We discuss how these defining features are established as cells transit from a stem cell character to that of a fully committed differentiating cell. The focus will be on how GSCs differentiate, via spermatogonia, to spermatocytes. We will achieve this by first describing the transcriptional activity in the differentiating spermatocytes, cataloguing the known transcriptional regulators in these cells and then investigating how the transcription programme is set up by processes in the progentior cells. This process is particularly interesting to study from a stem cell perspective as the male GSCs are unipotent, so lineage decisions in differentiating progeny of stem cells, which occurs in many other stem cell systems, do not impinge on the behaviour of these cells.

  15. Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery.

    PubMed

    Marchesi, Francesco; Mengarelli, Andrea

    2016-01-01

    To date, two kinds of Granulocyte Colony-Stimulating Factors (G-CSF) have been approved for autologous peripheral blood hematopoietic stem cell (PBSCs) mobilization and posttransplant hematologic recovery after high-dose chemotherapy: filgrastim (originator and biosimilar) and lenograstim. Biosimilar filgrastim has been approved on the basis of comparable efficacy and safety in clinical studies where it has been used as chemotherapy-induced febrile neutropenia prophylaxis, but no specific pre-registration studies have been published in the transplant setting. Hence, there is still general skepticism about the role of biosimilar G-CSFs in this setting of patients. This review of biochemical, pre-clinical and clinical data suggests significant comparability of biosimilar filgrastim with both originator filgrastim and lenograstim in autologous PBSCs mobilization and post-autograft hematologic recovery.

  16. Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy: an introduction for clinical researchers.

    PubMed

    Wei, Heming; Ooi, Ting Huay; Tan, Genevieve; Lim, Sze Yun; Qian, Ling; Wong, Philip; Shim, Winston

    2010-01-01

    Stem cell-based therapy for patients with post-infarct heart failure is a relatively new and revolutionary concept in cardiology. Despite the encouraging results from pre-clinical studies, outcomes from most clinical trials remain moderately positive while the clinical benefits are largely attributed to transplanted cell-associated paracrine effects in stimulating angiogenesis and protecting endogenous cardiomyocytes. This scenario indicates that there may be a considerably protracted iterative process of conceptual and procedural refinement before true clinical benefits can be fully materialized. At present, many pressing questions regarding cell therapy remain unanswered. In addition to the primary interest in determining the ideal type of stem cells with best cardiogenic potential in vitro and in vivo, there are growing concerns on the impact of the host cardiac milieu on the transplanted cells, including their survival, migration, engraftment, and trans-differentiation as well as contribution to left ventricular function. Effective cell delivery and tracking methods are central to the unraveling of these questions. To date, cell-delivery modalities are yet to be optimized and strategies for safe and effective assessment of cells transplanted in the recipients are to be established. In this review, we discuss cell delivery and tracking modalities that are adopted in the current pre-clinical and clinical studies. We further discussed emerging technologies that are poised to impact the success of cell therapy.

  17. Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency Using Post-Transplantation Cyclophosphamide.

    PubMed

    Shah, Nirali N; Freeman, Alexandra F; Su, Helen; Cole, Kristen; Parta, Mark; Moutsopoulos, Niki M; Baris, Safa; Karakoc-Aydiner, Elif; Hughes, Thomas E; Kong, Heidi H; Holland, Steve M; Hickstein, Dennis D

    2017-03-10

    Dedicator-of-Cytokinesis-8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplant (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/CY) for GVHD prophylaxis. Seven patients with DOCK8 deficiency (median age 20 years, range 7-25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, three days of busulfan, and 200 cGy TBI. Graft-versus host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (PT/CY) 50 mg/kg/day on days +3 and +4, and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (one with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range 9.5 - 31.7 months), 6 of 7 patients are alive and disease-free. Haploidentical related donor HSCT with PT/CY represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor.

  18. Mesenchymal stem cells in post-surgical cavities of large maxillary bone lesions

    PubMed Central

    Bertolai, Roberto; Catelani, Carlo; Signorini, Mattia; Rossi, Alessandro; Giannini, Domenico

    2016-01-01

    Summary Background Recent studies have highlighted that MSCs are capable of regenerating large bone defects when used in combination with bone substitutes and increasing allo-graft osteointegration. We investigated the hypothesis that autologous MSCs may lead to increased bone regeneration and reduced healing time in post-surgical cavities of large maxillary bone lesions. Methods This study involved 10 patients (TEST GROUP) (6 males and 4 females). All patients had expansive mandibular lesions larger than 3 cm. From the surgical point of view, the 10 patients were treated with MSCs (withdrawal of the iliac crest bone marrow BMMSs) directly into the post-surgical cavity, without the addition of filler. Results and radiological data, in the postoperative, were compared to those of patients who did not receive any grafting of MSCs. The 7 patients with mandibular lesions showed a rapid and very good healing with an 85–90% ossification of the major defect at 12 months. Conclusions Through the use of stem cells a greater ossification of the residual cavity (85–90%) was observed at 12 months after surgical enucleation in contenitive defects. PMID:28228785

  19. Accumulation efficiency of cancer stem-like cells post γ-ray and proton irradiation

    NASA Astrophysics Data System (ADS)

    Quan, Yi; Wang, Weikang; Fu, Qibin; Mei, Tao; Wu, Jingwen; Li, Jia; Yang, Gen; Wang, Yugang

    2012-09-01

    Ionizing radiation (IR) has been proven to be a powerful medical treatment in cancer therapy. Rational and effective use of its killing power depends on understanding IR-mediated responses at the molecular, cellular and tissue levels. Increasing evidence supports that cancer stem-like cells (CSCs) play an important role in tumor regrowth and spread post radiotherapy, for they are resistant to various therapy methods including radiation. Presently, SW620 colon carcinoma monolayer culture cells were irradiated with γ-rays and protons of 2 Gy. Then apoptosis, clonogenic survival and the expression of CD133+ protein were examined. The results showed that there was no significantly difference either on long-term clonogenic survival or on short-term apoptosis ratio. However, compared with γ-rays, irradiation with protons was less efficient to accumulate CSCs at the same dose, although both protons and γ-rays can significantly accumulate the CD133+ CSCs subpopulation. In addition, the results of sphere formation assay also confirmed that proton irradiation is less efficient in CSCs accumulation, suggesting proton irradiation might have higher efficiency in CSCs elimination for cancer radiotherapy.

  20. Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.

    PubMed

    Cieri, Nicoletta; Greco, Raffaella; Crucitti, Lara; Morelli, Mara; Giglio, Fabio; Levati, Giorgia; Assanelli, Andrea; Carrabba, Matteo G; Bellio, Laura; Milani, Raffaella; Lorentino, Francesca; Stanghellini, Maria Teresa Lupo; De Freitas, Tiago; Marktel, Sarah; Bernardi, Massimo; Corti, Consuelo; Vago, Luca; Bonini, Chiara; Ciceri, Fabio; Peccatori, Jacopo

    2015-08-01

    Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.

  1. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Luznik, Leo

    2010-01-01

    Graft-versus-host disease, or GVHD, is a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of hematologic malignancies. Here, we describe a novel method for preventing GVHD after alloHSCT using high-dose, post-transplantation cyclophosphamide (Cy). Post-transplantation Cy promotes tolerance in alloreactive host and donor T cells, leading to suppression of both graft rejection and GVHD after alloHSCT. High-dose, post-transplantation Cy facilitates partially HLA-mismatched HSCT without severe GVHD and is effective as sole prophylaxis of GVHD after HLA-matched alloHSCT. By reducing the morbidity and mortality of alloHSCT, post-transplantation Cy may expand the applications of this therapy to the treatment of autoimmune diseases and non-malignant hematologic disorders such as sickle cell disease. PMID:20066512

  2. Alternative donor hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for nonmalignant disorders

    PubMed Central

    Klein, Orly R.; Chen, Allen R.; Gamper, Christopher; Loeb, David; Zambidis, Elias; Llosa, Nicolas; Huo, Jeffrey; Dezern, Amy E.; Steppan, Diana; Robey, Nancy; Holuba, Mary Jo; Cooke, Kenneth R.; Symons, Heather J.

    2016-01-01

    Allogeneic (allo-) hematopoietic stem cell transplant (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft versus host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable to that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted eleven pediatric patients with life-threatening nonmalignant conditions using reduced intensity conditioning (RIC), alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allo-HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted. PMID:26860634

  3. Post implantation fate of adipogenic induced mesenchymal stem cells on Type I collagen scaffold in a rat model.

    PubMed

    Venugopal, Balu; Fernandez, Francis B; Harikrishnan, V S; John, Annie

    2017-02-01

    Regenerative medicine via its application in soft tissue reconstruction through novel methods in adipose tissue engineering (ATE) has gained remarkable attention and investment despite simultaneous reports on clinical incidence of graft resorption and impaired vascularization. The underlying malaise here once identified may play a critical role in optimizing implant function. Our work attempts to determine the fate of donor cells and the implant in recipient micro environment using adipose-derived mesenchymal stem cells (ASCs) on a type I collagen sponge, an established scaffold for ATE. Cell components within the construct were identified 21 days post implantation to delineate cell survival, proliferation & terminal roles in vivo. ASC's are multipotent, while collagen type I is a natural extra cellular matrix component. Commercially available bovine type I collagen was characterized for its physiochemical properties and cyto-compatibility. Nile red staining of induced ASCs identified red globular structures in cell cytoplasm indicating oil droplet accumulation. Similarly, in vivo implantation of the cell seeded collagen construct in rat model for 21 days in the dorsal muscle, showed genesis of chicken wire network of fat-like cells, which was demonstrated histologically using a variety of staining techniques. Furthermore, fluorescent in situ hybridization (FISH) technique established the efficiency of transplantation wherein the male donor cells with labeled Y chromosome was identified 21 days post implantation from female rat model. Retrieved samples at 21 days indicated adipogenesis in situ, with donor cells highlighted via FISH. The study provides an insight to stem cells in ATE from genesis to functionalization.

  4. Post-allogeneic Hematopoietic Stem Cell Transplantation (HSCT) changes in inorganic salivary components.

    PubMed

    Boer, C C; Correa, M E P; Tenuta, L M A; Souza, C A; Vigorito, A C

    2015-09-01

    Recent studies have considered the qualitative and quantitative assessment of salivary flow, as well the biochemical components of saliva, as possible biomarkers that might contribute to the pathogenesis of chronic graft-versus-host disease (cGHVD) in hematopoietic stem cell transplantation (HSCT) patients. The aim of this study was to evaluate prospectively the inorganic salivary status at different periods of allogeneic HSCT. Saliva collection and oral examination were performed prior to the HSCT, ​between days 8 and 10, days 80 and 100, and at the cGVHD onset. Concentrations of calcium (Ca), phosphate (Pi), chloride (Cl), magnesium (Mg), potassium (K), and sodium (Na) were performed using colorimetric reactions and atomic absorption. Fifty-five consecutive patients undergoing first allogeneic HSCT were included in this study. Between days 8 and 10, the salivary flow rate was significantly higher (p = 0.05), Pi concentration was decreased (p = 0.007), and Na and Cl were increased (p = 0.001 and p = 0.001, respectively), compared with the baseline. Salivary flow rate during the same period showed a negative correlation with Pi concentration (p = 0.02) and a positive correlation with Na and Cl concentrations (p = 0.003 and p = 0.001, respectively). The salivary flow rate was decreased between days 80 and 100 (p = 0.02) and Na, Cl, and K concentrations were increased (p = 0.03, p = 0.02, and p = 0.003, respectively). Salivary flow rate showed a negative correlation with Na and Cl (p = 0.01 and p = 0.013, respectively). At cGVHD onset, the salivary flow rate showed no statistical difference compared with the other studied periods. A trend was observed in the higher Na concentration compared with the baseline (p = 0.06) and Pi concentration presented a significant decrease (p = 0.004). Ca and Mg concentrations showed no changes during all evaluation periods. The present study showed changes in inorganic

  5. Stem Cell Information: Glossary

    MedlinePlus

    ... cells (skeletal stem cells) Cell-based therapies Cell culture Cell division Chromosome Clone Cloning Cord blood stem cells Culture medium Differentiation Directed differentiation DNA Ectoderm Embryo Embryoid ...

  6. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2009-01-23

    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.

  7. Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation.

    PubMed

    Stewart, F M; Temeles, D; Lowry, P; Thraves, T; Grosh, W W; Quesenberry, P J

    1993-05-01

    The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP-CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL-1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with

  8. Stem Cell Basics

    MedlinePlus

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  9. Induced pluripotent stem cell intervention rescues ventricular wall motion disparity, achieving biological cardiac resynchronization post-infarction

    PubMed Central

    Yamada, Satsuki; Nelson, Timothy J; Kane, Garvan C; Martinez-Fernandez, Almudena; Crespo-Diaz, Ruben J; Ikeda, Yasuhiro; Perez-Terzic, Carmen; Terzic, Andre

    2013-01-01

    Dyssynchronous myocardial motion aggravates cardiac pump function. Cardiac resynchronization using pacing devices is a standard-of-care in the management of heart failure. Post-infarction, however, scar tissue formation impedes the efficacy of device-based therapy. The present study tests a regenerative approach aimed at targeting the origin of abnormal motion to prevent dyssynchronous organ failure. Induced pluripotent stem (iPS) cells harbour a reparative potential, and were here bioengineered from somatic fibroblasts reprogrammed with the stemness factors OCT3/4, SOX2, KLF4, and c-MYC. In a murine infarction model, within 30 min of coronary ligation, iPS cells were delivered to mapped infarcted areas. Focal deformation and dysfunction underlying progressive heart failure was resolved prospectively using speckle-tracking imaging. Tracked at high temporal and spatial resolution, regional iPS cell transplantation restored, within 10 days post-infarction, the contractility of targeted infarcted foci and nullified conduction delay in adjacent non-infarcted regions. Local iPS cell therapy, but not delivery of parental fibroblasts or vehicle, prevented or normalized abnormal strain patterns correcting the decrease in peak strain, disparity of time-to-peak strain, and pathological systolic stretch. Focal benefit of iPS cell intervention translated into improved left ventricular conduction and contractility, reduced scar, and reversal of structural remodelling, protecting from organ decompensation. Thus, in ischaemic cardiomyopathy, targeted iPS cell transplantation synchronized failing ventricles, offering a regenerative strategy to achieve biological resynchronization. PMID:23568891

  10. Immune recovery and the risk of CMV/ EBV reactivation in children post allogeneic haematopoietic stem cell transplantation

    PubMed Central

    Janeczko, Małgorzata; Mielcarek, Monika; Rybka, Blanka; Ryczan-Krawczyk, Renata; Noworolska-Sauren, Dorota

    2016-01-01

    Immune reconstitution was studied prospectively in 86 children who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We analysed the risk of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence the reactivation of these viruses including: diagnosis, type of HSCT, source of stem cells, type of conditioning, or the occurrence of graft-versus-host disease (GvHD). The absolute number of lymphocyte subpopulations in peripheral blood was evaluated in seven timepoints following HSCT. Significantly lower values of both CD3+ and CD3+CD8+ lymphocytes on day +14 and significantly higher values of both these subsets on day +168 post-transplant in patients with CMV reactivation were observed. Significantly lower values of CD3+CD4+ subpopulation were noted in patients with CMV reactivation on day +28 post allo-HSCT. Significantly lower lymphocyte values in the group with EBV reactivation comparing with the group without EBV reactivation were confirmed only in the case of pan-B lymphocytes (CD19+) subpopulation on day +21, +28, and +84 post allo-HSCT. We identified the impact of CMV reactivation on occurrence of the intestinal acute GvHD, which occurred more frequently in the group with CMV reactivation compared with patients without reactivation. Higher incidence of chronic GvHD was also observed in patients with CMV reactivation compared to the group without reactivation. EBV reactivation occurred more frequently in patients receiving transplants from matched unrelated donors, in particular after peripheral blood stem cell transplantation and while implementing antithymocyte globulin as GvHD prophylaxis. PMID:27833447

  11. Characterization and comparison of post-natal rat Achilles tendon-derived stem cells at different development stages.

    PubMed

    Chen, Jialin; Zhang, Wei; Liu, Zeyu; Zhu, Ting; Shen, Weiliang; Ran, Jisheng; Tang, Qiaomei; Gong, Xiaonan; Backman, Ludvig J; Chen, Xiao; Chen, Xiaowen; Wen, Feiqiu; Ouyang, Hongwei

    2016-03-14

    Tendon stem/progenitor cells (TSPCs) are a potential cell source for tendon tissue engineering. The striking morphological and structural changes of tendon tissue during development indicate the complexity of TSPCs at different stages. This study aims to characterize and compare post-natal rat Achilles tendon tissue and TSPCs at different stages of development. The tendon tissue showed distinct differences during development: the tissue structure became denser and more regular, the nuclei became spindle-shaped and the cell number decreased with time. TSPCs derived from 7 day Achilles tendon tissue showed the highest self-renewal ability, cell proliferation, and differentiation potential towards mesenchymal lineage, compared to TSPCs derived from 1 day and 56 day tissue. Microarray data showed up-regulation of several groups of genes in TSPCs derived from 7 day Achilles tendon tissue, which may account for the unique cell characteristics during this specific stage of development. Our results indicate that TSPCs derived from 7 day Achilles tendon tissue is a superior cell source as compared to TSPCs derived from 1 day and 56 day tissue, demonstrating the importance of choosing a suitable stem cell source for effective tendon tissue engineering and regeneration.

  12. Innovations in Training: Toward Mitigating "Eternal post-docdum" in Stem Cell Research.

    PubMed

    Jacob, K J; Roskams-Edris, D; Illes, Judy

    2015-12-01

    The Networks of Centres of Excellence (NCE) is an innovative model of large-scale research networks that began in Canada in 1989, and has since been adopted by numerous countries around the globe. The Canadian Stem Cell Network (SCN), an NCE that has fostered stem cell research and innovation in Canada, has supported over 1800 trainees since its inception in 2001. In the present study we assess the impact of such a network on its research trainees professional decision-making and movements. A database populated by the SCN between the years 2001-2013 was utilized to describe trainee professional movement between sectors and geographic regions. Focus groups of SCN trainees (n = 27) were carried out and major themes and subthemes were derived from the discourse using a thematic analysis approach. We found that most SCN trainees remained in Canada and in academic positions after leaving the SCN. Trainees expressed a desire to work in environments where their scientific interests and ideas are nurtured, where funding is stable, and where supervisor mentorship is readily accessible. SCN trainees value the unique opportunities provided by the NCE, including opportunities to network with peers, to attend various workshops and to broaden their knowledge and interest base beyond science and academia. Challenges faced by postdoctoral fellows and recommendations for future NCEs are also discussed. The findings here can be used to form evidence-based recommendations for future research networks and for policy pertaining to the recruitment and retention of highly qualified personnel in stem cell research.

  13. Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer

    PubMed Central

    Bagó, Juli R.; Pegna, Guillaume J.; Okolie, Onyi; Hingtgen, Shawn D.

    2016-01-01

    Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC-sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types. PMID:26803410

  14. Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer.

    PubMed

    Bagó, Juli R; Pegna, Guillaume J; Okolie, Onyi; Hingtgen, Shawn D

    2016-04-01

    Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC-sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types.

  15. Freezing of Fresh Wharton's Jelly From Human Umbilical Cords Yields High Post-Thaw Mesenchymal Stem Cell Numbers for Cell-Based Therapies.

    PubMed

    Fong, Chui-Yee; Subramanian, Arjunan; Biswas, Arijit; Bongso, Ariff

    2016-04-01

    Some cord blood banks freeze entire pieces of UC (mixed cord, MC) which after post-thaw yields mixed heterogeneous populations of mesenchymal stem cells (MSCs) from all its microanatomical compartments. Freezing of such entire tissues results in sub-optimal post-thaw cell recovery because of poor cryoprotectant diffusion and intracellular ice-formation, heat and water transport issues, and damage to intercellular junctions. To develop a simple method of harvesting pure homogeneous MSCs for cord blood banks, we compared the post-thaw behavior of three groups of frozen UC tissues: (i) freshly harvested WJ without cell separation; (ii) MSCs isolated from WJ (WJSC); and (iii) MC, WJ, and WJSC produced high post-thaw cell survival rates (93.52 ± 6.12% to 90.83 ± 4.51%) and epithelioid monolayers within 24 h in primary culture whereas post-thaw MC explants showed slow growth with mixed epithelioid and fibroblastic cell outgrowths after several days. Viability and proliferation rates of post-thawed WJ and hWJSC were significantly greater than MC. Post-thaw WJ and WJSC produced significantly greater CD24(+) and CD108(+) fluorescence intensities and significantly lower CD40(+) contaminants. Post-thaw WJ and WJSC produced significantly lesser annexin-V-positive and sub-G1 cells and greater degrees of osteogenic and chondrogenic differentiation compared to MC. qRT-PCR analysis of post-thaw MC showed significant decreases in anti-apoptotic gene expression (SURVIVIN, BCL2) and increases in pro-apoptotic (BAX) and cell cycle regulator genes (P53, P21, ROCK 1) compared to WJ and WJSC. We conclude that freezing of fresh WJ is a simple and reliable method of generating large numbers of clinically utilizable MSCs for cell-based therapies.

  16. Stem Cell Sciences plc.

    PubMed

    Daniels, Sebnem

    2006-09-01

    Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

  17. Late-onset hepatic veno-occlusive disease post autologous peripheral stem cell transplantation successfully treated with oral defibrotide.

    PubMed

    Shah, Mithun S; Jeevangi, Nandish Kumar S; Joshi, Amit; Khattry, Navin

    2009-01-01

    Hepatic veno-occlusive disease (VOD) remains one of the commonest and most serious complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the finding of the triad of painful hepatomegaly, hyperbilirubinemia, and unexplained fluid retention occurring within 21 days of the transplant. However, the uncommon clinical entity of late-onset VOD can occur even beyond 20 days and should be considered in the differential diagnosis of any liver disease of more than 3 weeks' duration. While mild cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide, a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. We describe a patient who presented 55 days post transplant with clinical features suggestive of VOD. Upon treatment with oral defibrotide, he showed complete resolution of the VOD.

  18. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  19. Wound Healing Immediately Post-Thermal Injury Is Improved by Fat and Adipose Derived Stem Cell Isografts

    PubMed Central

    Loder, Shawn; Peterson, Jonathan R.; Agarwal, Shailesh; Eboda, Oluwatobi; Brownley, Cameron; DeLaRosa, Sara; Ranganathan, Kavitha; Cederna, Paul; Wang, Stewart C.; Levi, Benjamin

    2014-01-01

    Objectives Patients with severe burns suffer functional, structural, and aesthetic complications. It is important to explore reconstructive options given that no ideal treatment exists. Transfer of adipose and adipose-derived stem cells (ASCs) has been shown to improve healing in various models. We hypothesize that use of fat isografts and/or ASCs will improve healing in a mouse model of burn injury. Methods Twenty 6–8 week old C57BL/6 male mice received a 30% surface area partial-thickness scald burn. Adipose tissue and ASCs from inguinal fat pads were harvested from a second group of C57BL/6 mice. Burned mice received 500μl subcutaneous injection at burn site of 1) processed adipose, 2) ASCs, 3) mixed adipose (adipose and ASCs), or 4) sham (saline) injection (n=5/group) on the first day post-injury. Mice were followed by serial photography until sacrifice at days 5 and 14. Wounds were assessed for burn depth and healing by Hematoxylin and Eosin (H&E) and immunohistochemistry. Results All treated groups showed improved healing over controls defined by decreased wound depth, area, and apoptotic activity. After 5 days, mice receiving ASCs or mixed adipose displayed a non-significant improvement in vascularization. No significant changes in proliferation were noted at 5 days. Conclusions Adipose isografts improve some early markers of healing post-burn injury. We demonstrate that addition of these grafts improve specific structural markers of healing. This improvement may be due to an increase in early wound vascularity post-graft. Further studies are needed to optimize use of fat or ASC grafts in acute and reconstructive surgery. PMID:25185931

  20. Clinicopathologic spectrum and EBV status of post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Chen, Ding-Bao; Song, Qiu-Jing; Chen, Yun-Xin; Chen, Yu-Hong; Shen, Dan-Hua

    2013-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) are serious, life-threatening complications of solid-organ transplantation (SOT) and bone marrow transplantation, and are associated with high mortality. PTLDs represent a heterogeneous group of lymphoproliferative diseases, which show a spectrum of clinical, morphologic, and molecular genetic features ranging from reactive polyclonal lesions to frank lymphomas. We describe clinicopathologic features of 17 cases of PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which were analyzed by in situ hybridization for EBV and a panel of antibodies directed against numerous antigens, including CD20, PAX5, CD3, bcl-6, CD10, MUM-1/IRF4, CD138, Kappa, Lambda, CD30, CD15, and Ki67. The cases included 13 males and 4 females with a median age of 31 years (range 9-49 years) and the PTLDs developed 1.5-19 months post-transplant (mean 4.7 months). The histological types indicated five cases of early lesions, two of plasmacytic hyperplasia and three of infectious mononucleosis-like PTLD. Eight cases were polymorphic PTLD, and four were monomorphic PTLD, including three of diffuse large B cell lymphoma, and one of plasmablastic lymphoma. Foci and sheets of necrosis were observed in five cases. The infected ratio of EBV was 88.2 %. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion, or anti-CD20 monoclonal rituximab. Eight cases died. The first half year after allo-HSCT is very important for the development of PTLD. The diagnosis of PTLD relies on morphology and immunohistochemistry, and EBV plays an important role in the pathogenesis of PTLD. The prognosis of PTLD is poor, and, notably, PTLD after allo-HSCT exhibits some features different from those of PTLD after SOT.

  1. Lasers, stem cells, and COPD

    PubMed Central

    2010-01-01

    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. PMID:20158898

  2. Liver cancer stem cells.

    PubMed

    Sell, Stewart; Leffert, Hyam L

    2008-06-10

    In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

  3. Stem Cell Transplant

    MedlinePlus

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  4. Exploring the Content of Post-Traumatic Stress Symptoms among Parents after Paediatric Stem Cell Transplant

    PubMed Central

    Forinder, Ulla; Claesson, Lovisa; Szybek, Katharina; Lindahl Norberg, Annika

    2015-01-01

    In the present study the aim was to explore the content in a trauma reported in a self-report questionnaire by parents of children with a life threatening illness. Semi-structured interviews were performed, with the aim to explore the specific cognitive and behavioral content of the trauma related symptoms reported by the individual informant. The transcripts of the interviews were analyzed with content analysis using a direct approach with a-priori categories according to the B and C categories of the DSM-IV diagnostic criteria for PTSD. The results give us the picture of a complex situation, where the self-report instrument PCL captured a spectrum of qualitatively different cognitions. The parents described traumatic thoughts and images relating not only to experiences in the past (i.e., truly post-traumatic), but also to current stressors and expected future events. PMID:25965909

  5. Post-autologous stem cell transplantation administration of rituximab improves the outcome of patients with aggressive B cell non-Hodgkin's lymphoma.

    PubMed

    Tsirigotis, Panagiotis; Dray, Liliane; Resnick, Igor B; Ackerstein, Aliza; Gesundheit, Benjamin; Elad, Sharon; Or, Reuven; Shapira, Michael-Yechiel

    2010-03-01

    The major cause of treatment failure following high-dose therapy with autologous stem cell transplantation (ASCT) for aggressive B cell non-Hodgkin's lymphoma (NHL) is persistent disease or recurrence. We describe our experience with the administration of rituximab post-ASCT, either as maintenance therapy or for the treatment of relapsed disease in patients with aggressive B cell NHL. Fifty-six patients achieved complete remission post-transplant, and 19 of them received maintenance with rituximab. Maintenance with rituximab resulted in statistically significant superior outcome in terms of progression free (PFS; p = 0.002) and overall survival (OS; p = 0.011). The median PFS and OS of patients in the maintenance arm has not been reached yet, while the median PFS and OS of patients in the control arm were 29 and 42 months, respectively. Fifty-four patients had disease progression or relapsed post-ASCT, and 15 of them received rituximab in combination with chemo- and/or radiotherapy in order to achieve disease remission. Therapeutic administration of rituximab resulted in statistically significant prolongation of OS (p = 0.021). The median OS of patients treated with rituximab was 17 months, while median OS of patients in the control group was 10 months. We consider that the results of our study are promising but need to be verified within large randomized trials.

  6. Plant stem cell niches.

    PubMed

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  7. Induction of late graft-versus-host disease in a patient post-allogeneic stem cell transplantation by progesterone in conjunction with donor lymphocyte infusion.

    PubMed

    Gesundheit, Benjamin; Shapira, Michael Y; Maly, Alexander; Samuel, Simcha; Budowski, Einat; Or, Reuven

    2008-03-01

    Patients after stem cell transplantation (SCT), often develop graft-versus-host disease (GVHD) which, although potentially dangerous, is associated with the beneficial graft-versus-leukemia (GVL) effect. Where there is high risk of disease recurrence, donor lymphocyte infusions (DLI) are given to provide long-term disease control. We present a patient treated with DLI 4 years post-SCT, who developed acute GVHD after administration of progesterone to induce menstruation. This rare allergic reaction warrants further investigation.

  8. Nail stem cells.

    PubMed

    Sellheyer, Klaus

    2013-03-01

    Our knowledge on stem cells of the hair follicle has increased exponentially after the bulge was characterized as the stem cell niche two decades ago. In contrast, little is known about stem cells in the nail unit. Whereas hair follicles are plentiful and easy to access, the human body has only twenty nails and they are rarely biopsied. Therefore, examining fetal material offers unique advantages. In the following mini-review, our current knowledge on nail stem cells is summarized and analogies to the hair follicle stem cells are drawn.

  9. Post-transplant lymphoproliferative disease of donor origin, following haematopoietic stem cell transplantation in a patient with blastic plasmacytoid dendritic cell neoplasm.

    PubMed

    Piccin, Andrea; Morello, Enrico; Svaldi, Mirija; Haferlach, Torsten; Facchetti, Fabio; Negri, Giovanni; Vecchiato, Cinzia; Fisogni, Simona; Pusceddu, Irene; Cortelazzo, Sergio

    2012-12-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare condition that originates from dendritic cells. We report on the first case of Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disorder (PTLD) of donor origin in a BPDC patient post-allogeneic haematopoietic stem cell transplantation (HSCT). Flow cytometry study identified a cell population CD4+/CD56+/CD45RA+/CD123+/TCL1+ suggestive of BPDCN diagnosis, which was confirmed by a lymph node biopsy (cells positive for BCL11a, BDCA-2, CD2AP, CD123, TCL1 and S100). Cytogenetic analysis revealed a complex karyotype: (19 metaphase) 47,XX,t(1;6)(q21;q2?5),-13 + 2mar[11]/47, XX, +21 [3]/46,XX [5]. The patient was started on acute myeloid leukaemia (AML) induction schedule, and subsequently an allogeneic HSCT was performed. On day +36 post-HSCT, bone marrow biopsy/aspirate showed complete morphological remission, and chimerism study showed 100% donor chimera. However, on day +37, the patient was found to have enlarged cervical and supraclavicular lymphoadenopathy, splenomegaly and raised lactic dehydrogenase. EBV-DNA copies in blood were elevated, consistent with a lytic cycle. A lymph node biopsy showed EBV encoded RNA and large atypical B cells (CD45dim-, CD4+/CD56+, monoclonal for k-chain, CD19+/CD20+/CD21+/CD22+/CD38+/CD43+/CD79β-/CD5-/CD10-), consistent with PTLD monomorphic type. Chimerism study showed that PTLD was of donor origin. This case together with the recent literature findings on BPDCN and PTLD are discussed.

  10. Learn About Stem Cells

    MedlinePlus

    ... develops and ages, the number and type of stem cells changes. Totipotent cells are no longer present after dividing into the cells that generate the placenta and umbilical cord. Pluripotent cells ... organs and tissues. The stem cells that stay in your body throughout your ...

  11. Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach

    PubMed Central

    Thakkar, Umang G.; Vanikar, Aruna V.; Trivedi, Hargovind L.; Shah, Veena R.; Dave, Shruti D.; Dixit, Satyajit B.; Tiwari, Bharat B.; Shah, Harda H.

    2016-01-01

    Background: Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Materials and Methods: Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Results: Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 104/μL and mean CD34+ of 0.35%, CD45−/90+ and CD45−/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Conclusion: Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs. PMID:27110548

  12. The Structural Basis of Functional Improvement in Response to Human Umbilical Cord Blood Stem Cell Transplantation in Hearts with Post-Infarct LV Remodeling

    PubMed Central

    Chen, Yong; Ye, Lei; Zhong, Jia; Li, Xin; Yan, Chen; Chandler, Margaret P.; Calvin, Steve; Xiao, Feng; Negia, Mesfin; Low, Walter C.; Zhang, Jianyi; Yu, Xin

    2015-01-01

    Cellular therapy for myocardial repair has been one of the most intensely investigated interventional strategies for acute myocardium infarction. Although the therapeutic potential of stem cells has been demonstrated in various studies, the underlying mechanisms for such improvement are poorly understood. In the present study, we investigated the long-term effects of stem cell therapy on both myocardial fiber organization and regional contractile function using a rat model of post-infarct remodeling. Human non-hematopoietic umbilical cord blood stem cells (nh-UCBSCs) were administered via tail vein to rats 2 days after infarct surgery. Animals were maintained without immunosuppressive therapy. In vivo and ex vivo MR imaging was performed on infarct hearts ten months after cell transplantation. Compared to the age-matched rats exposed to the identical surgery, both global and regional cardiac function of the nh-UCBSC-treated hearts, such as ejection fraction, ventricular strain and torsion, were significantly improved. More importantly, the treated hearts exhibited preserved fiber orientation and water diffusivities that were similar to those in sham-operated control hearts. These data provide the first evidence that nh-UCBSC treatment may prevent/delay untoward structural remodeling in post-infarct hearts, which supports the improved LV function observed in vivo in the absence of immunosuppression, suggesting a beneficial paracrine effect that occurred with the cellular therapy. PMID:24332083

  13. Stress and stem cells.

    PubMed

    Tower, John

    2012-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress.

  14. Colorectal cancer stem cells.

    PubMed

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  15. Intraoperative Stem Cell Therapy

    PubMed Central

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

    2013-01-01

    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. PMID:22809140

  16. Myeloproliferative neoplasm stem cells.

    PubMed

    Mead, Adam J; Mullally, Ann

    2017-03-23

    Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC.

  17. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  18. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants A ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  19. In situ cryopreservation of human embryonic stem cells in gas-permeable membrane culture cassettes for high post-thaw yield and good manufacturing practice.

    PubMed

    Amps, K J; Jones, M; Baker, D; Moore, H D

    2010-06-01

    The development of efficient and robust methods for the cryopreservation of human embryonic stem cells (hESCs) is important for the production of master and working cell banks for future clinical applications. Such methods must meet requirements of good manufacturing practice (GMP) and maintain genetic stability of the cell line. We investigated the culture of four Shef hESC lines in gas permeable 'culture cassettes' which met GMP compliance. hESCs adhered rapidly to the membrane and colonies displayed good proliferation and expansion. After 5-7 days of culture, hESCs were cryopreserved in situ using 10% dimethyl sulphoxide in foetal calf serum at approximately 1 degrees C/min. This method was compared with a control of standard flask culture and cryopreservation in vials. Post-thaw cassette culture displayed relative proliferation ratios (fold increase above flask/cryovial culture) of 114 (Shef 4), 8.2 (Shef 5), 195 (shef 6) and 17.5 (Shef 7). The proportion of cells expressing pluripotency markers after cryopreservation was consistently greater in cassette culture than for the control with the markers SSEA3 and SSEA4 exhibiting a significant increase (P> or =0.05). The efficiency of cell line culture in cassette was associated with the overall passage number of the cell line. The procedure enables cryopreservation of relatively large quantities of hESCs in situ, whilst returning high yields of viable, undifferentiated stem cells, thereby increasing capacity to scale up with greater efficacy.

  20. Hematopoietic Stem Cells Therapies.

    PubMed

    Chivu-Economescu, Mihaela; Rubach, Martin

    2017-01-01

    Stem cell-based therapies are recognized as a new way to treat various diseases and injuries, with a wide range of health benefits. The goal is to heal or replace diseased or destroyed organs or body parts with healthy new cells provided by stem cell transplantation. The current practical form of stem cell therapy is the hematopoietic stem cells transplant applied for the treatment of hematological disorders. There are over 2100 clinical studies in progress concerning hematopoietic stem cell therapies. All of them are using hematopoietic stem cells to treat various diseases like: cancers, leukemia, lymphoma, cardiac failure, neural disorders, auto-immune diseases, immunodeficiency, metabolic or genetic disorders. Several challenges are to be addressed prior to developing and applying large scale cell therapies: 1) to explain and control the mechanisms of differentiation and development toward a specific cell type needed to treat the disease, 2) to obtain a sufficient number of desired cell type for transplantation, 3) to overcome the immune rejection and 4) to show that transplanted cells fulfill their normal functions in vivo after transplants.

  1. Stem Cell Organoid Engineering

    PubMed Central

    Yin, Xiaolei; Mead, Benjamin E.; Safaee, Helia; Langer, Robert; Karp, Jeffrey M.; Levy, Oren

    2016-01-01

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies. PMID:26748754

  2. Engineering Stem Cell Organoids.

    PubMed

    Yin, Xiaolei; Mead, Benjamin E; Safaee, Helia; Langer, Robert; Karp, Jeffrey M; Levy, Oren

    2016-01-07

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies.

  3. [On plant stem cells and animal stem cells].

    PubMed

    You, Yun; Jiang, Chao; Huang, Lu-Qi

    2014-01-01

    A comparison of plant and animal stem cells can highlight core aspects of stem-cell biology. In both kingdoms, stem cells are defined by their clonogenic properties and are maintained by intercellular signals. The signaling molecules are different in plants and animals stem cell niches, but the roles of argonaute and polycomb group proteins suggest that there are some molecular similarities.

  4. Human fetal mesenchymal stem cells.

    PubMed

    O'Donoghue, Keelin; Chan, Jerry

    2006-09-01

    Stem cells have been isolated at all stages of development from the early developing embryo to the post-reproductive adult organism. However, the fetal environment is unique as it is the only time in ontogeny that there is migration of stem cells in large numbers into different organ compartments. While fetal neural and haemopoietic stem cells (HSC) have been well characterised, only recently have mesenchymal stem cells from the human fetus been isolated and evaluated. Our group have characterised in human fetal blood, liver and bone marrow a population of non-haemopoietic, non-endothelial cells with an immunophenotype similar to adult bone marrow-derived mesenchymal stem cells (MSC). These cells, human fetal mesenchymal stem cells (hfMSC), are true multipotent stem cells with greater self-renewal and differentiation capacity than their adult counterparts. They circulate in first trimester fetal blood and have been found to traffic into the maternal circulation, engrafting in bone marrow, where they remain microchimeric for decades after pregnancy. Though fetal microchimerism has been implicated in the pathogenesis of autoimmune disease, the biological role of hfMSC microchimerism is unknown. Potential downstream applications of hfMSC include their use as a target cell for non-invasive pre-natal diagnosis from maternal blood, and for fetal cellular and gene therapy. Using hfMSC in fetal therapy offers the theoretical advantages of avoidance of immune rejection, increased engraftment, and treatment before disease pathology sets in. Aside from allogeneic hfMSC in utero transplantation, the use of autologous hfMSC has been brought a step forward with the development of early blood sampling techniques, efficient viral transduction and clonal expansion. Work is ongoing to determine hfMSC fate post-transplantation in murine models of genetic disease. In this review we will examine what is known about hfMSC biology, as well as discussing areas for future research. The

  5. Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents post-traumatic arthritis

    PubMed Central

    Diekman, Brian O.; Wu, Chia-Lung; Louer, Craig R.; Furman, Bridgette D.; Huebner, Janet L.; Kraus, Virginia B.; Olson, Steven A.; Guilak, Farshid

    2014-01-01

    Joint injury dramatically enhances the onset of osteoarthritis (OA) and is responsible for an estimated 12% of OA. Post-traumatic arthritis (PTA) is especially common after intraarticular fracture, and no disease-modifying therapies are currently available. We hypothesized that the delivery of mesenchymal stem cells (MSCs) would prevent PTA by altering the balance of inflammation and regeneration after fracture of the mouse knee. Additionally, we examined the hypothesis that MSCs from the MRL/MpJ (MRL) “superhealer” mouse strain would show increased multilineage and therapeutic potentials as compared to those from C57BL/6 (B6) mice, as MRL mice have shown exceptional in vivo regenerative abilities. A highly purified population of MSCs was prospectively isolated from bone marrow using cell surface markers (CD45−/TER119−/PDGFRα+/Sca-1+). B6 MSCs expanded greater than 100,000 fold in three weeks when cultured at 2% oxygen and displayed greater adipogenic, osteogenic, and chondrogenic differentiation as compared to MRL MSCs. Mice receiving only a control saline injection after fracture demonstrated PTA after 8 weeks, but the delivery of 10,000 B6 or MRL MSCs to the joint prevented the development of PTA. Cytokine levels in serum and synovial fluid were affected by treatment with stem cells, including elevated systemic interleukin-10 at several time points. The delivery of MSCs did not reduce the degree of synovial inflammation but did show increased bone volume during repair. This study provides evidence that intra-articular stem cell therapy can prevent the development of PTA after fracture and has implications for possible clinical interventions after joint injury before evidence of significant OA. PMID:22889498

  6. Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses.

    PubMed

    Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald

    2011-07-01

    Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor.

  7. The evolving art of hematopoietic stem cell transplantation: translational research in post-transplant immune reconstitution and immunosuppression.

    PubMed

    Komanduri, Krishna V; Wieder, Eric D; Benjamin, Cara L; Levy, Robert B

    2013-12-01

    Allogeneic hematopoietic stem cell transplantation (SCT) offers the best chance for cure and/or long-term survival for a broad range of diseases, including many high-risk hematologic malignancies, bone marrow failure states and subsets of inherited metabolic diseases and hemoglobinopathies. Clinical advances in allogeneic SCT have resulted in dramatically improved clinical outcomes over the past two decades, resulting in a significant expansion of transplant utilization to many recipients who would previously have been excluded from consideration, including elderly recipients and individuals lacking matched sibling or unrelated donors. Despite these advances, significant clinical challenges remain, including delayed immune reconstitution and the frequent occurrence of acute and chronic graft-versus-host disease, especially in the unrelated donor transplant setting. Translational laboratory efforts, facilitated by technical advances in our ability to measure thymopoiesis and functional T cell subsets in humans, have resulted in an improved understanding of immune recovery and have provided novel insights that may lead to more rational and selective immunosuppression.

  8. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  9. The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function.

    PubMed

    Mayfield, Audrey E; Tilokee, Everad L; Latham, Nicholas; McNeill, Brian; Lam, Bu-Khanh; Ruel, Marc; Suuronen, Erik J; Courtman, David W; Stewart, Duncan J; Davis, Darryl R

    2014-01-01

    Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the integration of fibronectin and fibrinogen into a supportive intra-capsular matrix. Encapsulation maintained CSC viability under hypoxic stress conditions and, when compared to standard suspended CSC, media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, cardiac structure and function. Single cell encapsulation prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium.

  10. Reversing breast cancer stem cell into breast somatic stem cell.

    PubMed

    Wijaya, L; Agustina, D; Lizandi, A O; Kartawinata, M M; Sandra, F

    2011-02-01

    Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research.

  11. HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning.

    PubMed

    Sugita, Junichi; Kawashima, Naomi; Fujisaki, Tomoaki; Kakihana, Kazuhiko; Ota, Shuichi; Matsuo, Keitaro; Miyamoto, Toshihiro; Akashi, Koichi; Taniguchi, Shuichi; Harada, Mine; Teshima, Takanori

    2015-09-01

    Allogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versus-host disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT.

  12. CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches.

    PubMed

    Williams, Karin; Motiani, Karan; Giridhar, Premkumar Vummidi; Kasper, Susan

    2013-03-01

    The stem cell niche provides a regulatory microenvironment for cells as diverse as totipotent embryonic stem cells to cancer stem cells (CSCs) which exhibit stem cell-like characteristics and have the capability of regenerating the bulk of tumor cells while maintaining self-renewal potential. The transmembrane glycoprotein CD44 is a common component of the stem cell niche and exists as a standard isoform (CD44s) and a range of variant isoforms (CD44v) generated though alternative splicing. CD44 modulates signal transduction through post-translational modifications as well as interactions with hyaluronan, extracellular matrix molecules and growth factors and their cognate receptor tyrosine kinases. While the function of CD44 in hematopoietic stem cells has been studied in considerable detail, our knowledge of CD44 function in tissue-derived stem cell niches remains limited. Here we review CD44s and CD44v in both hematopoietic and tissue-derived stem cell niches, focusing on their roles in regulating stem cell behavior including self-renewal and differentiation in addition to cell-matrix interactions and signal transduction during cell migration and tumor progression. Determining the role of CD44 and CD44v in normal stem cell, CSC and (pre)metastatic niches and elucidating their unique functions could provide tools and therapeutic strategies for treating diseases as diverse as fibrosis during injury repair to cancer progression.

  13. Multipotent Stem Cell and Reproduction.

    PubMed

    Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sobhani, Aligholi

    2016-01-01

    Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. The accessibility and adaptability of these amazing cells create them a great therapeutic choice for different part of medical approaches, and it becomes interesting topic in the scientific researches to found obvious method for the most advantageous use of MSC-based therapies. Recent studies in the field of stem cell biology have provided new perspectives and opportunities for the treatment of infertility disorders.

  14. Stem cell mobilization.

    PubMed

    Cottler-Fox, Michele H; Lapidot, Tsvee; Petit, Isabelle; Kollet, Orit; DiPersio, John F; Link, Dan; Devine, Steven

    2003-01-01

    Successful blood and marrow transplant (BMT), both autologous and allogeneic, requires the infusion of a sufficient number of hematopoietic progenitor/stem cells (HPCs) capable of homing to the marrow cavity and regenerating a full array of hematopoietic cell lineages in a timely fashion. At present, the most commonly used surrogate marker for HPCs is the cell surface marker CD34, identified in the clinical laboratory by flow cytometry. Clinical studies have shown that infusion of at least 2 x 10(6) CD34(+) cells/kg recipient body weight results in reliable engraftment as measured by recovery of adequate neutrophil and platelet counts approximately 14 days after transplant. Recruitment of HPCs from the marrow into the blood is termed mobilization, or, more commonly, stem cell mobilization. In Section I, Dr. Tsvee Lapidot and colleagues review the wide range of factors influencing stem cell mobilization. Our current understanding focuses on chemokines, proteolytic enzymes, adhesion molecules, cytokines and stromal cell-stem cell interactions. On the basis of this understanding, new approaches to mobilization have been designed and are now starting to undergo clinical testing. In Section II, Dr. Michele Cottler-Fox describes factors predicting the ability to mobilize the older patient with myeloma. In addition, clinical approaches to improving collection by individualizing the timing of apheresis and adjusting the volume of blood processed to achieve a desired product are discussed. Key to this process is the daily enumeration of blood CD34(+) cells. Newer methods of enumerating and mobilizing autologous blood HPCs are discussed. In Section III, Dr. John DiPersio and colleagues provide data on clinical results of mobilizing allogeneic donors with G-CSF, GM-CSF and the combination of both as relates to the number and type of cells collected by apheresis. Newer methods of stem cell mobilization as well as the relationship of graft composition on immune reconstitution

  15. Cloning of Mammary Stem Cells

    DTIC Science & Technology

    2001-11-01

    these parity-induced cells do represent a totipotent mammary stem cell population per se, but these cells might support stem cell maintenance as... Stem Cells PRINCIPAL INVESTIGATOR: Dr. Kay-Uwe Wagner CONTRACTING ORGANIZATION: University of Nebraska Medical Center Omaha, Nebraska 68198-6810 REPORT...Mammary Stem Cells DAMD17-00-1-0641 6. AUTHOR(S) Dr. Kay-Uwe Wagner 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT

  16. Stem cells from deciduous tooth repair mandibular defect in swine.

    PubMed

    Zheng, Y; Liu, Y; Zhang, C M; Zhang, H Y; Li, W H; Shi, S; Le, A D; Wang, S L

    2009-03-01

    Stem cells from human exfoliated deciduous teeth have been identified as a new post-natal stem cell population with multipotential differentiation capabilities, including regeneration of mineralized tissues in vivo. To examine the efficacy of utilizing these stem cells in regenerating orofacial bone defects, we isolated stem cells from miniature pig deciduous teeth and engrafted the critical-size bone defects generated in swine mandible models. Our results indicated that stem cells from miniature pig deciduous teeth, an autologous and easily accessible stem cell source, were able to engraft and regenerate bone to repair critical-size mandibular defects at 6 months post-surgical reconstruction. This pre-clinical study in a large-animal model, specifically swine, allows for testing of a stem cells/scaffold construct in the restoration of orofacial skeletal defects and provides rapid translation of stem-cell-based therapy in orofacial reconstruction in human clinical trials.

  17. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  18. Sirolimus for Refractory Autoimmune Hemolytic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review of the Treatment of Post-Transplant Autoimmune Hemolytic Anemia.

    PubMed

    Park, Jeong A; Lee, Hyun-Hee; Kwon, Hyun-Seop; Baik, Chung-Ryul; Song, Sae-Am; Lee, Jung Nye

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) may occur after any type of allogeneic hematopoietic stem cell transplantation (HCT), even ABO-matched transplantation. It tends to be refractory to standard corticosteroid treatment and requires multiple transfusions. Though, there is no consensus regarding the optimal treatment for post-transplant severe AIHA. We present a pediatric patient with refractory AIHA after umbilical cord blood transplantation. She developed severe AIHA at 3months after transplantation and was unresponsive to multiple treatment modalities, including corticosteroids, intravenous immunoglobulin, plasma exchange and rituximab, resulting in persistent transfusion dependency. Sirolimus, a mammalian target of rapamycin inhibitor, was started on day 67 after the onset of AIHA, and this patient was successfully rescued without any complications. Sirolimus induces apoptosis in autoreactive lymphocytes, increases regulatory T cells and has been reported to have a positive effect on AIHA following solid organ transplantation (SOT). We reviewed the literature regarding post-transplant AIHA in the PubMed database and evaluated the treatment outcome of sirolimus in AIHA after SOT.

  19. Fifth Annual Stem Cell Summit.

    PubMed

    Knowlton, Daniel

    2010-04-01

    The Fifth Annual Stem Cell Summit, held in New York, included topics covering new commercial developments in the research field of stem cell-based therapies. This conference report highlights selected presentations on embryonic and adult stem cells, stem cell-based therapies for the treatment of orthopedic and cardiovascular indications and inflammatory diseases, as well as technologies for processing and storing stem cells. Investigational therapies discussed include placental expanded (PLX) cells (Pluristem Therapeutics Inc), StemEx (Gamida-Teva Joint Venture/Teva Pharmaceutical Industries Ltd) and remestemcel-L (Osiris Therapeutics Inc/Genzyme Corp/JCR Pharmaceuticals Co Ltd/ Mochida Pharmaceutical Co Ltd).

  20. Stem Cell Transplants (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Stem Cell Transplants KidsHealth > For Parents > Stem Cell Transplants A A A What's in this article? ... Recovery Coping en español Trasplantes de células madre Stem cells are cells in the body that have the ...

  1. Stem cells and transplant arteriosclerosis.

    PubMed

    Xu, Qingbo

    2008-05-09

    Stem cells can differentiate into a variety of cells to replace dead cells or to repair damaged tissues. Recent evidence indicates that stem cells are involved in the pathogenesis of transplant arteriosclerosis, an alloimmune initiated vascular stenosis that often results in transplant organ failure. Although the pathogenesis of transplant arteriosclerosis is not yet fully understood, recent developments in stem cell research have suggested novel mechanisms of vascular remodeling in allografts. For example, stem cells derived from the recipient may repair damaged endothelial cells of arteries in transplant organs. Further evidence suggests that stem cells or endothelial progenitor cells may be released from both bone marrow and non-bone marrow tissues. Vascular stem cells appear to replenish cells that died in donor vessels. Concomitantly, stem/progenitor cells may also accumulate in the intima, where they differentiate into smooth muscle cells. However, several issues concerning the contribution of stem cells to the pathogenesis of transplant arteriosclerosis are controversial, eg, whether bone marrow-derived stem cells can differentiate into smooth muscle cells that form neointimal lesions of the vessel wall. This review summarizes recent research on the role of stem cells in transplant arteriosclerosis, discusses the mechanisms of stem cell homing and differentiation into mature endothelial and smooth muscle cells, and highlights the controversial issues in the field.

  2. Laser biomodulation on stem cells

    NASA Astrophysics Data System (ADS)

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

    2001-08-01

    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 the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

  3. [Stem cell colloquy: conclusion].

    PubMed

    Tubiana, Maurice

    2002-10-01

    The stem cell data presented and discussed during the symposium raise the hope that important medical progress can be made in several fields: neuro-degenerative diseases, those linked to cellular deficit, some aspects of aging linked to cellular degeneration, and the treatment of cancers that may harm normal tissues at risk of being infiltrated by malignant cells. Three main types of stem cells are available. (i) Those present in normal adult tissue: contrary to what was believed, some data suggest that certain adult stem cells have a great plasticity (they can differentiate into cells different from those in tissues from which they were taken) and can proliferate in vitro without losing their properties. Nevertheless, their use faces several obstacles: in ill or elderly subjects, then these cells can be limited in number or not multiply well in vitro. In this case, auto-grafting of the cells cannot be used. They must be sought in another subject, and allo-grafting causes difficult and sometimes insoluble problems of immunological tolerance. (ii) Embryonic stem cells from surplus human embryos, obtained by in vitro fertilisation, which the parents decide not to use: these cells have a great potential for proliferation and differentiation, but can also encounter problems of immunological intolerance. (iii) Cells obtained from cell nuclear transfer in oocytes: these cells are well tolerated, since they are genetically and immunologically identical to those of the host. All types of stem cells can be obtained with them. However, they do present problems. For obtaining them, female oocytes are needed, which could lead to their commercialization. Moreover, the first steps for obtaining these cells are identical to those used in reproductive cloning. It therefore appears that each type of cell raises difficult scientific and practical problems. More research is needed to overcome these obstacles and to determine which type of stem cell constitutes the best solution for

  4. Neural stem cells: an overview.

    PubMed

    Parati, E A; Pozzi, S; Ottolina, A; Onofrj, M; Bez, A; Pagano, S F

    2004-01-01

    Multipotent stem cells are present in the majority of mammalian tissues where they are a renewable source of specialized cells. According to the several biological portions from which multipotent stem cells can be derived, they are characterized as a) embryonic stem cells (ESCs) isolated from the pluripotent inner-cell mass of the pre-implantation blastocyste-stage embryo; b) multipotent fetal stem cells (FSCs) from aborted fetuses; and c) adult stem cells (ASCs) localized in small zones of several organs known as "niche" where a subset of tissue cells and extracellular substrates can indefinitely house one or more stem cells and control their self-renewal and progeny production in vivo. ECSs have an high self-renewing capacity, plasticity and pluripotency over the years. Pluripotency is a property that makes a stem cell able to give rise to all cell type found in the embryo and adult animals.

  5. Representations of stem cell clinics on Twitter.

    PubMed

    Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

    2014-12-01

    The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients.

  6. Stem cells and healthy aging.

    PubMed

    Goodell, Margaret A; Rando, Thomas A

    2015-12-04

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.

  7. Stem Cells and Female Reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    Several recent findings in stem cell biology have resulted in new opportunities for the treatment of reproductive disease. Endometrial regeneration can be driven by bone marrow derived stem cells. This finding has potential implications for the treatment of uterine disorders. It also supports a new theory for the etiology of endometriosis. The ovaries have been shown to contain stem cells that form oocytes in adults and can be cultured in vitro to develop mature oocytes. Stem cells from the fetus have been demonstrated to lead to microchimerism in the mother and implicated in several maternal diseases. Additionally the placenta may be another source of hematopoietic stem cell. Finally endometrial derived stem cells have been demonstrated to differentiate into non-reproductive tissues. While we are just beginning to understand stem cells and many key questions remain, the potential advantages of stem cells in reproductive biology and medicine are apparent. PMID:19208782

  8. Inflammation and cancer stem cells.

    PubMed

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche.

  9. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  10. Materials as stem cell regulators

    PubMed Central

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

    2014-01-01

    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

  11. Materials as stem cell regulators

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    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.

  12. Information on Stem Cell Research

    MedlinePlus

    ... Home » Current Research » Focus on Research Focus on Stem Cell Research Stem cells possess the unique ability to differentiate into many ... they also retain the ability to produce more stem cells, a process termed self-renewal. There are multiple ...

  13. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

    PubMed Central

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P.; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-01-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. PMID:27365460

  14. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

    PubMed

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-07-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.

  15. Medaka haploid embryonic stem cells.

    PubMed

    Hong, Yunhan

    2010-01-01

    The appearance of diploidy, the presence of two genomes or chromosome sets, is a fundamental hallmark of eukaryotic evolution and bisexual reproduction, because diploidy offers the basis for the bisexual life cycle, allowing for oscillation between diploid and haploid phases. Meiosis produces haploid gametes. At fertilization, male and female gametes fuse to restore diploidy in a zygote, which develops into a new life. At sex maturation, diploid cells enter into meiosis, culminating in the production of haploid gametes. Therefore, diploidy ensures pluripotency, cell proliferation, and functions, whereas haploidy is restricted only to the post-meiotic gamete phase of germline development and represents the end point of cell growth. Diploidy is advantageous for evolution. Haploidy is ideal for genetic analyses, because any recessive mutations of essential genes will show a clear phenotype in the absence of a second gene copy. Recently, my laboratory succeeded in the generation of medaka haploid embryonic stem (ES) cells capable of whole animal production. Therefore, haploidy in a vertebrate is able to support stable cell culture and pluripotency. This finding anticipates the possibility to generate haploid ES cells in other vertebrate species such as zebrafish. These medaka haploid ES cells elegantly combine haploidy and pluripotency, offering a unique yeast-like system for in vitro genetic analyses of molecular, cellular, and developmental events in various cell lineages. This chapter is aimed to describe the strategy of haploid ES cell derivation and their characteristics, and illustrate the perspectives of haploid ES cells for infertility treatment, genetic screens, and analyses.

  16. Stem cells in dentistry--part I: stem cell sources.

    PubMed

    Egusa, Hiroshi; Sonoyama, Wataru; Nishimura, Masahiro; Atsuta, Ikiru; Akiyama, Kentaro

    2012-07-01

    Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties.

  17. Measuring stem cell circadian rhythm.

    PubMed

    Hrushesky, William; Rich, Ivan N

    2015-01-01

    Circadian rhythms are biological rhythms that occur within a 24-h time cycle. Sleep is a prime example of a circadian rhythm and with it melatonin production. Stem cell systems also demonstrate circadian rhythms. This is particularly the case for the proliferating cells within the system. In fact, all proliferating cell populations exhibit their own circadian rhythm, which has important implications for disease and the treatment of disease. Stem cell chronobiology is particularly important because the treatment of cancer can be significantly affected by the time of day a drug is administered. This protocol provides a basis for measuring hematopoietic stem cell circadian rhythm for future stem cell chronotherapeutic applications.

  18. Breast Cancer Stem Cells

    PubMed Central

    Velasco-Velázquez, Marco A.; Homsi, Nora; De La Fuente, Marisol; Pestell, Richard G.

    2012-01-01

    Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44+/CD24−/low or ALDH+ phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics have identified NF-κB, c-Jun, p21CIP1, and Forkhead-like-protein Dach1 in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs. PMID:22249027

  19. Regulation of Mammary Stem Cell Quiescence via Post-Translational Modification of DeltaNp63alpha

    DTIC Science & Technology

    2014-02-01

    Additionally, when we transfected an ALK5-GFP fusion expression vector into H1299 cells and subsequently treated with vehicle or TGFβ, we were able to...show that the fusion protein localizes to the nucleus (Appendix1: Figure 6D). This nuclear accumulation was also found to occur with endogenous ALK5... cervical carcinomas and 28.5% of lung squamous cell carcinomas (http://cbioportal. PLOS ONE | www.plosone.org 1 November 2012 | Volume 7 | Issue 11 | e50066

  20. (Re)defining stem cells.

    PubMed

    Shostak, Stanley

    2006-03-01

    Stem-cell nomenclature is in a muddle! So-called stem cells may be self-renewing or emergent, oligopotent (uni- and multipotent) or pluri- and totipotent, cells with perpetual embryonic features or cells that have changed irreversibly. Ambiguity probably seeped into stem cells from common usage, flukes in biology's history beginning with Weismann's divide between germ and soma and Haeckel's biogenic law and ending with contemporary issues over the therapeutic efficacy of adult versus embryonic cells. Confusion centers on tissue dynamics, whether stem cells are properly members of emerging or steady-state populations. Clarity might yet be achieved by codifying differences between cells in emergent populations, including embryonic stem and embryonic germ (ES and EG) cells in tissue culture as opposed to self-renewing (SR) cells in steady-state populations.

  1. Pancreatic cancer stem cells.

    PubMed

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

    Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever.

  2. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    DTIC Science & Technology

    2012-07-01

    into anabolic therapies for osteoporosis .1 Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a...research into anabolic therapies for osteoporosis .1 Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases...13. SUPPLEMENTARY NOTES 14. ABSTRACT Osteoporosis , both age-related and post-menopausal, is a huge health problem in the United States and indeed

  3. Nuclear receptor regulation of stemness and stem cell differentiation

    PubMed Central

    Jeong, Yangsik

    2009-01-01

    Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cells and tissue-specific adult stem cells. Here, we review the role of the NR superfamily in various aspects of stem cell biology, including their regulation of stemness, forward- and trans-differentiation events; reprogramming of terminally differentiated cells; and interspecies differences. These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell). PMID:19696553

  4. Aging, metabolism and stem cells: Spotlight on muscle stem cells.

    PubMed

    García-Prat, Laura; Muñoz-Cánoves, Pura

    2017-04-15

    All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population.

  5. Stem Cells, Redox Signaling, and Stem Cell Aging

    PubMed Central

    Liang, Raymond

    2014-01-01

    Abstract Significance: Functional stem cell decline has been postulated to result in loss of maintenance of tissue homeostasis leading to organismal decline and diseases of aging. Recent Advances: Recent findings implicate redox metabolism in the control of stem cell pool and stem cell aging. Although reactive oxygen species (ROS) are better known for their damaging properties to DNA, proteins and lipids, recent findings suggest that ROS may also be an integral physiological mediator of cellular signaling in primary cells. Critical Issues: Here we review recent published work on major signaling pathways and transcription factors that are regulated by ROS and mediate ROS regulation of stem cell fate. We will specifically focus on how alterations in this regulation may be implicated in disease and particularly in diseases of stem cell aging. In general, based on the work described here we propose a model in which ROS function as stem cell rheostat. Future Directions: Future work in elucidating how ROS control stem cell cycling, apoptotic machinery, and lineage determination should shed light on mechanisms whereby ROS may control stem cell aging. Antioxid. Redox Signal. 20, 1902–1916. PMID:24383555

  6. FACS Sorting Mammary Stem Cells.

    PubMed

    Iriondo, Oihana; Rábano, Miriam; Vivanco, María D M

    2015-01-01

    Fluorescent-activated cell sorting (FACS) represents one of the key techniques that have been used to isolate and characterize stem cells, including cells from the mammary gland. A combination of approaches, including recognition of cell surface antigens and different cellular activities, has facilitated the identification of stem cells from the healthy mammary gland and from breast tumors. In this chapter we describe the protocol to use FACS to separate breast cancer stem cells, but most of the general principles discussed could be applied to sort other types of cells.

  7. Targeting prostate cancer stem cells.

    PubMed

    Crea, Francesco; Mathews, Lesley A; Farrar, William L; Hurt, Elaine M

    2009-12-01

    Cancer stem cells are the sub-population of cells present within tumors responsible for tumorigenesis. These cells have unique biological properties including self-renewal and the ability to differentiate. Furthermore, it is thought that these cells are more resistant to conventional chemotherapy and, as a result, are responsible for patient relapse. We will discuss the identification of prostate cancer stem cells, their unique properties and how these cells may be targeted for more efficacious therapies.

  8. Stem cells for spine surgery

    PubMed Central

    Schroeder, Joshua; Kueper, Janina; Leon, Kaplan; Liebergall, Meir

    2015-01-01

    In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer’s disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion. PMID:25621119

  9. Stem Cells behind the Barrier

    PubMed Central

    Cangkrama, Michael; Ting, Stephen B.; Darido, Charbel

    2013-01-01

    Epidermal stem cells sustain the adult skin for a lifetime through self-renewal and the production of committed progenitors. These stem cells generate progeny that will undergo terminal differentiation leading to the development of a protective epidermal barrier. Whereas the molecular mechanisms that govern epidermal barrier repair and renewal have been extensively studied, pathways controlling stem cell differentiation remain poorly understood. Asymmetric cell divisions, small non-coding RNAs (microRNAs), chromatin remodeling complexes, and multiple differentiation factors tightly control the balance of stem and progenitor cell proliferation and differentiation, and disruption of this balance leads to skin diseases. In this review, we summarize and discuss current advances in our understanding of the mechanisms regulating epidermal stem and progenitor cell differentiation, and explore new relationships for maintenance of skin barrier function. PMID:23812084

  10. [Stem cell therapy: an update].

    PubMed

    Coulombel, Laure

    2009-03-01

    Medicine will be faced with a major challenge in coming years, namely how to treat for tissue dysfunction due to disease and aging There are two basic options: drug therapy and cell therapy. Stem cells have been the subject of intense speculation and controversy for several years, as they open up radically new therapeutic possibilities. Classical drugs can only smoothen consequences of tissue dysfunction, whereas cell therapy has the potential to restore tissue function by providing fresh cells. Cell therapy is totally different from organ transplantation, which can only benefit a limited number of patients. The use of the generic term "stem cells" to designate a whole variety of cell types that are present throughout life, is a source of confusion and ambiguity. It will take years of cognitive research to unravel the molecular mechanisms that govern a stem cell's multi- or totipotent status before we can fully exploit this therapeutic tool to the full. The younger a stem cell the greater its potential and, probably, the more durable its benefits, but the use of embryonic stem cells raises ethical issues. The redundancy or equivalence of diferent categories of cells is another source of controversy, yet researchers must be able to study stem cells in all their diversity, as complementary rather than competitive alternatives, in an acceptable ethical and regulatory environment. We briefly describe the three types of stem cells: pluripotent embryonic stem cells, fetal and adult stem cells, and pluripotent reprogrammed adult somatic cells. Only the former two categories have physiological functions: the first gives rise to tissues and organs while the second maintains tissue function during adulthood

  11. Stem cells in pharmaceutical biotechnology.

    PubMed

    Zuba-Surma, Ewa K; Józkowicz, Alicja; Dulak, Józef

    2011-11-01

    Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All

  12. The advantages of hair follicle pluripotent stem cells over embryonic stem cells and induced pluripotent stem cells for regenerative medicine.

    PubMed

    Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2010-12-01

    Multipotent adult stem cells have many potential therapeutic applications. Our recent findings suggest that hair follicles are a promising source of easily accessible multipotent stem cells. Stem cells in the hair follicle area express the neural stem cell marker nestin, suggesting that hair-follicle stem cells and neural stem cells have common features. Nestin-expressing hair follicle stem cells can form neurons and other cell types, and thus adult hair follicle stem cells could have important therapeutic applications, particularly for neurologic diseases. Transplanted hair follicle stem cells promote the functional recovery of injured peripheral nerve and spinal cord. Recent findings suggest that direct transplantation of hair-follicle stem cells without culture can promote nerve repair, which makes them potentially clinically practical. Human hair follicle stem cells as well as mouse hair follicle stem cells promote nerve repair and can be applied to test the hypothesis that human hair follicle stem cells can provide a readily available source of neurologically therapeutic stem cells. The use of hair follicle stem cells for nerve regeneration overcomes critical problems of embryonic stem cells or induced pluripotent stem cells in that the hair follicle stem cells are multipotent, readily accessible, non-oncogenic, and are not associated with ethical issues.

  13. Stem cell mitochondria during aging.

    PubMed

    Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Shyh-Chang, Ng

    2016-04-01

    Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future.

  14. Immune privilege of stem cells.

    PubMed

    Ichiryu, Naoki; Fairchild, Paul J

    2013-01-01

    Immune privilege provides protection to vital tissues or cells of the body when foreign antigens are introduced into these sites. The modern concept of relative immune privilege applies to a variety of tissues and anatomical structures, including the hair follicles and mucosal surfaces. Even sites of chronic inflammation and developing tumors may acquire immune privilege by recruiting immunoregulatory effector cells. Adult stem cells are no exception. For their importance and vitality, many adult stem cell populations are believed to be immune privileged. A preimplantation-stage embryo that derives from a totipotent stem cell (i.e., a fertilized oocyte) must be protected from maternal allo-rejection for successful implantation and development to occur. Embryonic stem cells, laboratory-derived cell lines of preimplantation blastocyst-origin, may, therefore, retain some of the immunological properties of the developing embryo. However, embryonic stem cells and their differentiated tissue derivatives transplanted into a recipient do not necessarily have an ability to subvert immune responses to the extent required to exploit their pluripotency for regenerative medicine. In this review, an extended definition of immune privilege is developed and the capacity of adult and embryonic stem cells to display both relative and acquired immune privilege is discussed. Furthermore, we explore how these intrinsic properties of stem cells may one day be harnessed for therapeutic gain.

  15. On hematopoietic stem cell fate.

    PubMed

    Metcalf, Donald

    2007-06-01

    Multipotential hematopoietic stem cells (HSCs) maintain blood-cell formation throughout life. Here, Metcalf considers the origin and heterogeneity of HSCs, their ability to self-generate, and their commitment to the various hematopoietic lineages.

  16. Gastrointestinal stem cell up-to-date.

    PubMed

    Pirvulet, V

    2015-01-01

    Cellular and tissue regeneration in the gastrointestinal tract depends on stem cells with properties of self-renewal, clonogenicity, and multipotency. Progress in stem cell research and the identification of potential gastric, intestinal, colonic stem cells new markers and the signaling pathways provide hope for the use of stem cells in regenerative medicine and treatments for disease. This review provides an overview of the different types of stem cells, focusing on tissue-restricted adult stem cells.

  17. Hematopoetic stem cell transplantation in children

    PubMed Central

    Yeşilipek, Mehmet Akif

    2014-01-01

    Bone marrow transplantation is called hematopoetic stem cell transplantation (HSCT), since peripheral blood and umbilical cord blood can also be used as sources of stem cell currently. In children, bone marrow transplantation is used as a definite treatment method in many diseases including hemoglobinopaties, immune deficiencies, bone marrow failure and congenital metabolic diseases in addition to hematological malignancies. In addition to the underlying disease, the most important factors which have an impact on prognosis include infections which develop during the process of transplantation and graft-versus-host disease. In this article, it was aimed to give brief information on stem cell sources, preparation therapies, HSCT indications and post-transplantation complications in children. PMID:26078642

  18. A Comparison of Culture Characteristics between Human Amniotic Mesenchymal Stem Cells and Dental Stem Cells.

    PubMed

    Yusoff, Nurul Hidayat; Alshehadat, Saaid Ayesh; Azlina, Ahmad; Kannan, Thirumulu Ponnuraj; Hamid, Suzina Sheikh Abdul

    2015-04-01

    In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells.

  19. Germline and Pluripotent Stem Cells.

    PubMed

    Reik, Wolf; Surani, M Azim

    2015-11-02

    Epigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of the totipotent state, which in turn leads to the establishment of pluripotent cells in blastocysts. The latter are the cells from which pluripotent embryonic stem cells are derived and maintained in culture. Following blastocyst implantation, postimplantation epiblast cells develop, which give rise to all somatic cells as well as primordial germ cells, the precursors of sperm and eggs. Pluripotent stem cells in culture can be induced to undergo differentiation into somatic cells and germ cells in culture. Understanding the natural cycles of epigenetic reprogramming that occur in the germline will allow the generation of better and more versatile stem cells for both therapeutic and research purposes.

  20. Bone repair and stem cells.

    PubMed

    Ono, Noriaki; Kronenberg, Henry M

    2016-10-01

    Bones are an important component of vertebrates; they grow explosively in early life and maintain their strength throughout life. Bones also possess amazing capabilities to repair-the bone is like new without a scar after complete repair. In recent years, a substantial progress has been made in our understanding on mammalian bone stem cells. Mouse genetic models are powerful tools to understand the cell lineage, giving us better insights into stem cells that regulate bone growth, maintenance and repair. Recent findings about these stem cells raise new questions that require further investigations.

  1. Bone regeneration and stem cells

    PubMed Central

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  2. GPCRs in Stem Cell Function

    PubMed Central

    DOZE, VAN A.; PEREZ, DIANNE M.

    2013-01-01

    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. PMID:23415095

  3. Plant and animal stem cells: similar yet different.

    PubMed

    Heidstra, Renze; Sabatini, Sabrina

    2014-05-01

    The astonishingly long lives of plants and their regeneration capacity depend on the activity of plant stem cells. As in animals, stem cells reside in stem cell niches, which produce signals that regulate the balance between self-renewal and the generation of daughter cells that differentiate into new tissues. Plant stem cell niches are located within the meristems, which are organized structures that are responsible for most post-embryonic development. The continuous organ production that is characteristic of plant growth requires a robust regulatory network to keep the balance between pluripotent stem cells and differentiating progeny. Components of this network have now been elucidated and provide a unique opportunity for comparing strategies that were developed in the animal and plant kingdoms, which underlie the logic of stem cell behaviour.

  4. Stem cell therapy without the cells

    PubMed Central

    Maguire, Greg

    2013-01-01

    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. PMID:24567776

  5. Myocardial infarction: stem cell transplantation for cardiac regeneration.

    PubMed

    Carvalho, Edmund; Verma, Paul; Hourigan, Kerry; Banerjee, Rinti

    2015-11-01

    It is estimated that by 2030, almost 23.6 million people will perish from cardiovascular disease, according to the WHO. The review discusses advances in stem cell therapy for myocardial infarction, including cell sources, methods of differentiation, expansion selection and their route of delivery. Skeletal muscle cells, hematopoietic cells and mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs)-derived cardiomyocytes have advanced to the clinical stage, while induced pluripotent cells (iPSCs) are yet to be considered clinically. Delivery of cells to the sites of injury and their subsequent retention is a major issue. The development of supportive scaffold matrices to facilitate stem cell retention and differentiation are analyzed. The review outlines clinical translation of conjugate stem cell-based cellular therapeutics post-myocardial infarction.

  6. Stem cells and combinatorial science.

    PubMed

    Fang, Yue Qin; Wong, Wan Qing; Yap, Yan Wen; Orner, Brendan P

    2007-09-01

    Stem cell-based technologies have the potential to help cure a number of cell degenerative diseases. Combinatorial and high throughput screening techniques could provide tools to control and manipulate the self-renewal and differentiation of stem cells. This review chronicles historic and recent progress in the stem cell field involving both pluripotent and multipotent cells, and it highlights relevant cellular signal transduction pathways. This review further describes screens using libraries of soluble, small-molecule ligands, and arrays of molecules immobilized onto surfaces while proposing future trends in similar studies. It is hoped that by reviewing both the stem cell and the relevant high throughput screening literature, this paper can act as a resource to the combinatorial science community.

  7. Stem Cells in the Lung

    PubMed Central

    Liu, Xiaoming; Driskell, Ryan R.; Engelhardt, John F.

    2007-01-01

    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. PMID:17141060

  8. In-Hospital Mortality and Post-Transplant Complications in Elderly Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: a Population-Based Study.

    PubMed

    Sanchez, Larysa; Sylvester, Michael; Parrondo, Ricardo; Mariotti, Veronica; Eloy, Jean Anderson; Chang, Victor T

    2017-03-09

    Autologous hematopoietic stem cell transplantation (auto-HSCT) has improved survival in patients with multiple myeloma (MM) and is increasingly used in elderly patients. The aim of this study was to characterize and compare in-hospital complications and mortality after auto-HSCT in younger (< age 65) vs. elderly (≥ age 65) MM patients utilizing the Nationwide Inpatient Sample (NIS). Over a three-year period (2008-2010), 2209 patients with MM were admitted to U.S. Hospitals for auto-HSCT. The median age was 59 years, with 1650 patients (74.7%) younger than age 65 and 559 patients (25.3%) age 65 or older. Overall, in-hospital mortality in MM patients following auto-HSCT was rare (1.5%) and there was no significant difference in mortality between elderly and younger patients. Elderly patients did have a significantly increased mean length of stay (18.6 days + 10.8 days (standard deviation) vs. 16.8 days + 7.2 days, p<0.001) and mean total hospital charges ($161,117 + $105,008 vs. $151,192 + $78,342, p=0.018) compared to younger pts. Elderly patients were significantly more likely than younger patients to develop major in-hospital post-transplant complications such as severe sepsis (OR 2.70, 95% CI: 1.40-5.21, p=0.003), septic shock, (OR 3.10, 95% CI: 1.43-6.71, p=0.004), pneumonia (OR 1.62, 95% CI: 1.06-2.46, p=0.024), acute respiratory failure (OR 3.44, 95% CI: 1.70-6.96, p=0.001), endotracheal intubation requiring prolonged mechanical ventilation (OR 2.19, 95% CI: 1.06-4.55, p=0.035), acute renal failure (OR 2.14, 95% CI: 1.38-3.33, p=0.001), and cardiac arrhythmias (OR 2.06, 95% CI: 1.52-2.79, <0.001). This data may help guide informed consent discussions and provide a focus for future studies to reduce treatment-related morbidity in elderly MM patients undergoing auto-HSCT.

  9. Dental stem cells and their sources.

    PubMed

    Sedgley, Christine M; Botero, Tatiana M

    2012-07-01

    The search for more accessible mesenchymal stem cells than those found in bone marrow has propelled interest in dental tissues. Human dental stem/progenitor cells (collectively termed dental stem cells [DSCs]) that have been isolated and characterized include dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, periodontal ligament stem cells, and dental follicle progenitor cells. Common characteristics of these cell populations are the capacity for self-renewal and the ability to differentiate into multiple lineages. In vitro and animal studies have shown that DSCs can differentiate into osseous, odontogenic, adipose, endothelial, and neural-like tissues.

  10. Modeling Stem Cell Myogenic Differentiation

    PubMed Central

    Deshpande, Rajiv S.; Spector, Alexander A.

    2017-01-01

    The process of stem cell myogenesis (transformation into skeletal muscle cells) includes several stages characterized by the expression of certain combinations of myogenic factors. The first part of this process is accompanied by cell division, while the second part is mainly associated with direct differentiation. The mechanical cues are known to enhance stem cell myogenesis, and the paper focuses on the stem cell differentiation under the condition of externally applied strain. The process of stem cell myogenic differentiation is interpreted as the interplay among transcription factors, targeted proteins and strain-generated signaling molecule, and it is described by a kinetic multi-stage model. The model parameters are optimally adjusted by using the available data from the experiment with adipose-derived stem cells subjected to the application of cyclic uniaxial strains of the magnitude of 10%. The modeling results predict the kinetics of the process of myogenic differentiation, including the number of cells in each stage of differentiation and the rates of differentiation from one stage to another for different strains from 4% to 16%. The developed model can help better understand the process of myogenic differentiation and the effects of mechanical cues on stem cell use in muscle therapies. PMID:28106095

  11. Diabetes and Stem Cell Function

    PubMed Central

    Fujimaki, Shin; Wakabayashi, Tamami; Takemasa, Tohru; Asashima, Makoto; Kuwabara, Tomoko

    2015-01-01

    Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer's disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment. PMID:26075247

  12. Stem cell therapy for Parkinson's disease.

    PubMed

    Takahashi, Jun

    2007-06-01

    The aim of stem cell therapy for Parkinson's disease is to reconstruct nigro-striatal neuronal pathways using endogenous neural stem/precursor cells or grafted dopaminergic neurons. As an alternative, transplantation of stem cell-derived dopaminergic neurons into the striatum has been attempted, with the aim of stimulating local synapse formation and/or release of dopamine and cytokines from grafted cells. Candidate stem cells include neural stem/precursor cells, embryonic stem cells and other stem/precursor cells. Among these, embryonic stem cells are pluripotent cells that proliferate extensively, making them a good potential donor source for transplantation. However, tumor formation and ethical issues present major problems for embryonic stem cell therapy. This review describes the current status of stem cell therapy for Parkinson's disease, as well as future research approaches from a clinical perspective.

  13. Neural Stem Cells and Glioblastoma

    PubMed Central

    Rispoli, Rossella; Conti, Carlo; Celli, Paolo; Caroli, Emanuela; Carletti, Sandro

    2014-01-01

    Summary Glioblastoma multiforme represents one of the most common brain cancers with a rather heterogeneous cellular composition, as indicated by the term “multiforme". Recent reports have described the isolation and identification of cancer neural stem cells from human adult glioblastoma multiforme, which possess the capacity to establish, sustain, and expand these tumours, even under the challenging settings posed by serial transplantation experiments. Our study focused on the distribution of neural cancer stem cells inside the tumour. The study is divided into three phases: removal of tumoral specimens in different areas of the tumour (centre, periphery, marginal zone) in an operative room equipped with a 1.5 T scanner; isolation and characterization of neural cancer stem cells from human adult glioblastoma multiforme; identification of neural cancer stem cell distribution inside the tumour. PMID:24750704

  14. Stem cells, tissue engineering and periodontal regeneration.

    PubMed

    Han, J; Menicanin, D; Gronthos, S; Bartold, P M

    2014-06-01

    The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.

  15. [Progress in stem cells and regenerative medicine].

    PubMed

    Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

    2015-06-01

    Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

  16. Tracking stem cells in the cardiovascular system.

    PubMed

    Chemaly, Elie R; Yoneyama, Ryuichi; Frangioni, John V; Hajjar, Roger J

    2005-11-01

    Stem cells are a promising approach to cardiovascular therapeutics. Animal experiments have assessed the fate of injected stem cells through ex vivo methods on sacrificed animals. Approaches are needed for in vivo tracking of stem cells. Various imaging techniques and contrast agents for stem cell tracking will be reviewed.

  17. Immunotargeting of cancer stem cells

    PubMed Central

    Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

    2015-01-01

    Cancer stem cells (CSCs) represent a distinctive population of tumour cells that control tumour initiation, progression, and maintenance. Their influence is great enough to risk the statement that successful therapeutic strategy must target CSCs in order to eradicate the disease. Because cancer stem cells are highly resistant to chemo- and radiotherapy, new tools to fight against cancer have to be developed. Expression of antigens such as ALDH, CD44, EpCAM, or CD133, which distinguish CSCs from normal cells, together with CSC immunogenicity and relatively low toxicity of immunotherapies, makes immune targeting of CSCs a promising approach for cancer treatment. This review will present immunotherapeutic approaches using dendritic cells, T cells, pluripotent stem cells, and monoclonal antibodies to target and eliminate CSCs. PMID:25691822

  18. Stem cell potential of the mammalian gonad

    PubMed Central

    Liu, Chia-Feng; Barsoum, Ivraym; Gupta, Rupesh; Hofmann, Marie-Claude; Yao, Humphrey Hung-Chang

    2010-01-01

    Stem cells have enormous potential for therapeutic application because of their ability to self-renew and differentiate into different cell types. Gonads, which consist of somatic cells and germ cells, are the only organs capable of transmitting genetic materials to the offspring. Germ-line stem cells and somatic stem cells have been found in the testis; however, the presence of stem cells in the ovary remains controversial. In this review, we discuss studies focusing on whether stem cell properties are present in the different cell types of male and female gonads and their implications on stem cell research. PMID:19482665

  19. Stem cell applications in diabetes.

    PubMed

    Noguchi, Hirofumi

    2012-01-01

    Diabetes mellitus is a devastating disease and the World Health Organization (WHO) expects that the number of diabetic patients will increase to 300 million by the year 2025. Patients with diabetes experience decreased insulin secretion that is linked to a significant reduction in the number of islet cells. Type 1 diabetes is characterized by the selective destruction of pancreatic β cells caused by an autoimmune attack. Type 2 diabetes is a more complex pathology that, in addition to β cell loss caused by apoptotic programs, includes β cell de-differentiation and peripheric insulin resistance. The success achieved over the last few years with islet transplantation suggests that diabetes can be cured by the replenishment of deficient β cells. These observations are proof of the concept and have intensified interest in treating diabetes or other diseases not only by cell transplantation but also by stem cells. An increasing body of evidence indicates that, in addition to embryonic stem cells, several potential adult stem/progenitor cells derived from the pancreas, liver, spleen, and bone marrow could differentiate into insulin-producing cells in vitro or in vivo. However, significant controversy currently exists in this field. Pharmacological approaches aimed at stimulating the in vivo/ex vivo regeneration of β cells have been proposed as a way of augmenting islet cell mass. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. A new technology, known as protein transduction, facilitates the differentiation of stem cells into insulin-producing cells. Recent progress in the search for new sources of β cells has opened up several possibilities for the development of new treatments for diabetes.

  20. New Insights into Thyroid Stem Cells

    PubMed Central

    Lin, Reigh-Yi

    2009-01-01

    Stem cells exhibit an extraordinary ability for self-renewal. They also give rise to many specialized cells. The potential of stem cells in regenerative medicine, developmental biology, and drug discovery has been well documented. Although advances in stem cell science have raised broad ethical concerns, it is clear that stem cell technology has revolutionized our thinking in modern biology and medicine and provided the basis for understanding many of the mechanisms controlling basic biological processes and disease mechanisms. This review details the nascent field of thyroid stem cell research, exploring the current status of thyroid stem cell differentiation from the perspectives of both developmental biology and cell replacement therapy. It highlights successes to date in the generation of thyroid follicular cells from embryonic stem cells in the laboratory and the identification and characterization of adult stem cells from human thyroid glands and thyroid cancers. Finally, it outlines future challenges with a focus on potential stem cell therapy for thyroid patients. PMID:17727339

  1. Stem cell regulation: Implications when differentiated cells regulate symmetric stem cell division.

    PubMed

    Høyem, Marte Rørvik; Måløy, Frode; Jakobsen, Per; Brandsdal, Bjørn Olav

    2015-09-07

    We use a mathematical model to show that if symmetric stem cell division is regulated by differentiated cells, then changes in the population dynamics of the differentiated cells can lead to changes in the population dynamics of the stem cells. More precisely, the relative fitness of the stem cells can be affected by modifying the death rate of the differentiated cells. This result is interesting because stem cells are less sensitive than differentiated cells to environmental factors, such as medical therapy. Our result implies that stem cells can be manipulated indirectly by medical treatments that target the differentiated cells.

  2. Stem Cells and Liver Regeneration

    PubMed Central

    DUNCAN, ANDREW W.; DORRELL, CRAIG; GROMPE, MARKUS

    2011-01-01

    One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition. PMID:19470389

  3. Stem cells in pediatric cardiology.

    PubMed

    Patel, Pranali; Mital, Seema

    2013-10-01

    The ability to reprogram virtually any cell of human origin to behave like embryonic or pluripotent stem cells is a major breakthrough in stem cell biology. Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study "disease in a dish" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. They also provide an exciting opportunity for drug discovery and drug repurposing for disorders with a known molecular basis including childhood onset heart disease, particularly cardiac genetic disorders. The review will discuss their use in drug discovery, efficacy and toxicity studies with emphasis on challenges in pediatric-focused drug discovery. Issues that will need to be addressed in the coming years include development of maturation protocols for iPSC-derived cardiac lineages, use of iPSCs to study not just cardiac but extra-cardiac phenotypes in the same patient, scaling up of stem cell platforms for high-throughput drug screens, translating drug testing results to clinical applications in the paradigm of personalized medicine, and improving both the efficiency and the safety of iPSC-derived lineages for future stem cell therapies.

  4. [Therapeutic use of stem cells].

    PubMed

    Uzan, Georges

    2004-09-15

    Stem cells display important capacities of self renewing, proliferation and differentiation. Because those present in the embryo have the more remarkable properties, their potential use in the therapy of until now incurable degenerative diseases have been envisioned. Embryonic stem (ES) cells are located in the inner mass of the balstocyst at early stages of the development. Even in long-term cultures they still retain their undifferentiated features. Under specific culture conditions, ES cells can be committed into a variety of differentiation pathways, giving rise to large amounts of cells corresponding to different tissues (neurones, cardiomyocytes, skeletal muscle, etc.). However, producing these tissues from already established ES cell lines would lead to immune rejection when transplanted to patients. To prevent this pitfall and using the expertise accumulated by animal cloning by nucleus transfer, it has been proposed to adapt this technique to human ES cells. The therapeutic cloning consists in transferring the nucleus of somatic stem cells isolated from the patient into an enucleated oocyte, to allow blastocyst development from which ES cells will be derived. From these stem cells, compatible tissues will be then produced. The problem is that it is in theoretically possible to reimplant the cloned blastocyst into a surrogate mother for obtaining a baby genetically identical to the donor. This is called reproductive cloning. This worrying risk raises important ethic and legal questions.

  5. Epigenetics in cancer stem cells.

    PubMed

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  6. Stem cells' exodus: a journey to immortality.

    PubMed

    Zhou, Yi; Lewallen, Michelle; Xie, Ting

    2013-01-28

    Stem cell niches provide a regulatory microenvironment that retains stem cells and promotes self-renewal. Recently in Developmental Cell, Rinkevich et al. (2013) showed that cell islands (CIs) of Botryllus schlosseri, a colonial chordate, provide niches for maintaining cycling stem cells that migrate from degenerated CIs to newly formed buds.

  7. Stem-cell ecology and stem cells in motion

    PubMed Central

    Scadden, David T.

    2008-01-01

    This review highlights major scientific developments over the past 50 years or so in concepts related to stem-cell ecology and to stem cells in motion. Many thorough and eloquent reviews have been presented in the last 5 years updating progress in these issues. Some paradigms have been challenged, others validated, or new ones brought to light. In the present review, we will confine our remarks to the historical development of progress. In doing so, we will refrain from a detailed analysis of controversial data, emphasizing instead widely accepted views and some challenging novel ones. PMID:18398055

  8. Targeting Aggressive Cancer Stem Cells in Glioblastoma

    PubMed Central

    Seymour, Tracy; Nowak, Anna; Kakulas, Foteini

    2015-01-01

    Glioblastoma (GBM) is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM) is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12–15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem-like cells (GSCs) within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance, and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggest that GSCs share critical signaling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors, SOX2, OCT4, and Nanog homeobox, demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse, and achieve a cure for these patients. PMID:26258069

  9. Common stemness regulators of embryonic and cancer stem cells

    PubMed Central

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies. PMID:26516408

  10. Introduction to stem cells and regenerative medicine.

    PubMed

    Kolios, George; Moodley, Yuben

    2013-01-01

    Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent). There are several sources of stem cells with varying potencies. Pluripotent cells are embryonic stem cells derived from the inner cell mass of the embryo and induced pluripotent cells are formed following reprogramming of somatic cells. Pluripotent cells can differentiate into tissue from all 3 germ layers (endoderm, mesoderm, and ectoderm). Multipotent stem cells may differentiate into tissue derived from a single germ layer such as mesenchymal stem cells which form adipose tissue, bone, and cartilage. Tissue-resident stem cells are oligopotent since they can form terminally differentiated cells of a specific tissue. Stem cells can be used in cellular therapy to replace damaged cells or to regenerate organs. In addition, stem cells have expanded our understanding of development as well as the pathogenesis of disease. Disease-specific cell lines can also be propagated and used in drug development. Despite the significant advances in stem cell biology, issues such as ethical controversies with embryonic stem cells, tumor formation, and rejection limit their utility. However, many of these limitations are being bypassed and this could lead to major advances in the management of disease. This review is an introduction to the world of stem cells and discusses their definition, origin, and classification, as well as applications of these cells in regenerative medicine.

  11. Multipotent Stem Cell and Current Application.

    PubMed

    Sobhani, Aligholi; Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sargolzaei Aval, Fereydoon

    2017-01-01

    Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. Multipotent Stem cells have been applying in treatment of different disorders such as spinal cord injury, bone fracture, autoimmune diseases, rheumatoid arthritis, hematopoietic defects, and fertility preservation.

  12. Commercial Nanoparticles for Stem Cell Labeling and Tracking

    PubMed Central

    Wang, Yaqi; Xu, Chenjie; Ow, Hooisweng

    2013-01-01

    Stem cell therapy provides promising solutions for diseases and injuries that conventional medicines and therapies cannot effectively treat. To achieve its full therapeutic potentials, the homing process, survival, differentiation, and engraftment of stem cells post transplantation must be clearly understood. To address this need, non-invasive imaging technologies based on nanoparticles (NPs) have been developed to track transplanted stem cells. Here we summarize existing commercial NPs which can act as contrast agents of three commonly used imaging modalities, including fluorescence imaging, magnetic resonance imaging and photoacoustic imaging, for stem cell labeling and tracking. Specifically, we go through their technologies, industry distributors, applications and existing concerns in stem cell research. Finally, we provide an industry perspective on the potential challenges and future for the development of new NP products. PMID:23946821

  13. Stem cell cultivation in bioreactors.

    PubMed

    Rodrigues, Carlos A V; Fernandes, Tiago G; Diogo, Maria Margarida; da Silva, Cláudia Lobato; Cabral, Joaquim M S

    2011-01-01

    Cell-based therapies have generated great interest in the scientific and medical communities, and stem cells in particular are very appealing for regenerative medicine, drug screening and other biomedical applications. These unspecialized cells have unlimited self-renewal capacity and the remarkable ability to produce mature cells with specialized functions, such as blood cells, nerve cells or cardiac muscle. However, the actual number of cells that can be obtained from available donors is very low. One possible solution for the generation of relevant numbers of cells for several applications is to scale-up the culture of these cells in vitro. This review describes recent developments in the cultivation of stem cells in bioreactors, particularly considerations regarding critical culture parameters, possible bioreactor configurations, and integration of novel technologies in the bioprocess development stage. We expect that this review will provide updated and detailed information focusing on the systematic production of stem cell products in compliance with regulatory guidelines, while using robust and cost-effective approaches.

  14. Stem cells in orthopaedics and fracture healing.

    PubMed

    Alwattar, Basil J; Schwarzkopf, Ran; Kirsch, Thorsten

    2011-01-01

    Stem cell application is a burgeoning field of medicine that is likely to influence the future of orthopaedic surgery. Stem cells are associated with great promise and great controversy. For the orthopaedic surgeon, stem cells may change the way that orthopaedic surgery is practiced and the overall approach of the treatment of musculoskeletal disease. Stem cells may change the field of orthopaedics from a field dominated by surgical replacements and reconstructions to a field of regeneration and prevention. This review will introduce the basic concepts of stem cells pertinent to the orthopaedic surgeon and proceed with a more in depth discussion of current developments in the study of stem cells in fracture healing.

  15. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  16. Epigenetic Regulation of Hematopoietic Stem Cells

    PubMed Central

    Sharma, Shilpa; Gurudutta, Gangenahalli

    2016-01-01

    Hematopoietic stem cells are endowed with a distinct potential to bolster self-renewal and to generate progeny that differentiate into mature cells of myeloid and lymphoid lineages. Both hematopoietic stem cells and mature cells have the same genome, but their gene expression is controlled by an additional layer of epigenetics such as DNA methylation and post-translational histone modifications, enabling each cell-type to acquire various forms and functions. Until recently, several studies have largely focussed on the transcription factors andniche factors for the understanding of the molecular mechanisms by which hematopoietic cells replicate and differentiate. Several lines of emerging evidence suggest that epigenetic modifications eventually result in a defined chromatin structure and an “individual” gene expression pattern, which play an essential role in the regulation of hematopoietic stem cell self-renewal and differentiation. Distinct epigenetic marks decide which sets of genes may be expressed and which genes are kept silent. Epigenetic mechanisms are interdependent and ensure lifelong production of blood and bone marrow, thereby contributing to stem cell homeostasis. The epigenetic analysis of hematopoiesis raises the exciting possibility that chromatin structure is dynamic enough for regulated expression of genes. Though controlled chromatin accessibility plays an essential role in maintaining blood homeostasis; mutations in chromatin impacts on the regulation of genes critical to the development of leukemia. In this review, we explored the contribution of epigenetic machinery which has implications for the ramification of molecular details of hematopoietic self-renewal for normal development and underlying events that potentially co-operate to induce leukemia. PMID:27426084

  17. Targeting the pathway of GSK-3β/nerve growth factor to attenuate post-infarction arrhythmias by preconditioned adipose-derived stem cells.

    PubMed

    Lee, Tsung-Ming; Harn, Horng-Jyh; Chiou, Tzyy-Wen; Chuang, Ming-Hsi; Chen, Chun-Hung; Lin, Po-Cheng; Lin, Shinn-Zong

    2017-03-01

    Adipose-derived stem cell (ADSC) transplantation is a promising new therapy to improve cardiac function after myocardial infarction. However, its low efficacy of transdifferentiation hampers its usefulness. Glycogen synthase kinase-3β (GSK-3β) signal has been shown to play a role in preconditioning-induced cardioprotection. We assessed whether n-butylidenephthalide (BP) primed ADSCs can attenuate arrhythmias by a GSK-3β-dependent pathway after myocardial infarction. Male Wistar rats after coronary ligation was randomly allocated to receive intramyocardial injection of vehicle, ADSCs, BP-preconditioned ADSCs, (BP+lithium)-preconditioned ADSCs, (BP+SB216763)-preconditioned ADSCs, and (BP+LY294002)-preconditioned ADSCs. ADSCs were primed for 16h before implantation. After 4weeks of implantation, ADSCs were retained in myocardium, reduced fibrosis and improved cardiac function. Sympathetic hyperinnervation was blunted after administering ADSCs, assessed by immunofluorescent analysis, and Western blotting and real-time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during programmed stimulation in the ADSC-treated infarcted rats were significantly lower than vehicle. BP-preconditioned ADSCs had superior cardioprotection, greater ADSC engraftment and transdifferentiation, and antiarrhythmic effects compared with ADSCs alone. Simultaneously, BP increased the levels of phospho-Akt and down-regulated GSK-3β activity. The effects of BP against sympathetic hyperinnervation were blocked by LY294002, a PI3K inhibitor. Addition of either lithium or SB216763 did not have additional effects compared with BP alone. Compared with ADSC alone, BP-primed ADSC implantation improved stem cell engraftment and attenuated sympathetic hyperinnervation and arrhythmias through a PI3K/Akt/GSK-3β-dependent pathway, suggesting that a synergic action was achieved between BP pretreatment and ADSCs.

  18. Comparison of Three Distinct Prophylactic Agents Against Invasive Fungal Infections in Patients Undergoing Haplo-identical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

    PubMed Central

    El-Cheikh, Jean; Crocchiolo, Roberto; Vai, Andrea; Furst, Sabine; Bramanti, Stefania; Sarina, Barbara; Granata, Angela; Faucher, Catherine; Mohty, Bilal; Harbi, Samia; Bouabdallah, Reda; Vey, Norbert; Santoro, Armando; Chabannon, Christian; Castagna, Luca; Blaise, Didier

    2015-01-01

    Over the past decade, invasive fungal infections (IFIs) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to bedetermined. We conducted a retrospective analysis, comparing the safety and efficacy of micafungin 50mg/day vs. fluconazole 400mg/day vs. itraconazole 200mg/day as prophylaxis for adult patients with various haematological diseases receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) followed by high-dose cyclophosphamide (PT-Cy). Overall, 99 patients were identified: 30 patients received micafungin, 50 and 19 patients received itraconazole and fluconazole, respectively. After a median follow-up of 12 months (range: 1–51), proven or probable IFIs were reported in 3 patients (10%) in the micafungin, 5 patients in the itraconazole (10%) and 2 patients (11%) in the fluconazole group (p=0.998). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 3 [6%] in the itraconazole vs. 2 [11%] in the fluconazole group, p=0.589). Four patients (13%) in the micafungin group vs 13 (26%) patients in the itraconazole group and 10 (53%) patients in the fluconazole received empirical antifungal therapy (P = 0.19). No serious adverse events related to treatment were reported by patients, and there was no treatment discontinuation because of drug-related adverse events in both groups. The present analysis shows that micafungin did better than fluconazole in preventing invasive aspergillosis after transplant in these high-risk hematological diseases, as expected. In addition, micafungin was more effective than itraconazole in preventing all IFI episodes when also considering possible fungal infections. Future prospective studies would shed light on this issue, concerning this increasingly used transplant platform. PMID:26401237

  19. Adult stem cell therapy: dream or reality?

    PubMed

    Moraleda, Jose M; Blanquer, Miguel; Bleda, Patricia; Iniesta, Paqui; Ruiz, Francisco; Bonilla, Sonia; Cabanes, Carmen; Tabares, Lucía; Martinez, Salvador

    2006-12-01

    Adult stem cells may be an invaluable source of plastic cells for tissue regeneration. The bone marrow contains different subpopulations of adult stem cells easily accessible for transplantation. However the therapeutic value of adult stem cell is a question of debate in the scientific community. We have investigated the potential benefits of adult hematopoietic stem cell transplantation in animal models of demyelinating and motor neuron diseases. Our results suggest that transplantation of HSC have direct and indirect neuroregenerative and neuroprotective effects.

  20. Emerging molecular approaches in stem cell biology.

    PubMed

    Jaishankar, Amritha; Vrana, Kent

    2009-04-01

    Stem cells are characterized by their ability to self-renew and differentiate into multiple adult cell types. Although substantial progress has been made over the last decade in understanding stem cell biology, recent technological advances in molecular and systems biology may hold the key to unraveling the mystery behind stem cell self-renewal and plasticity. The most notable of these advances is the ability to generate induced pluripotent cells from somatic cells. In this review, we discuss our current understanding of molecular similarities and differences among various stem cell types. Moreover, we survey the current state of systems biology and forecast future needs and direction in the stem cell field.

  1. Mesenchymal Stem Cells as Therapeutics

    PubMed Central

    Parekkadan, Biju; Milwid, Jack M.

    2013-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID:20415588

  2. Ethics and Governance of Stem Cell Banks.

    PubMed

    Chalmers, Donald; Rathjen, Peter; Rathjen, Joy; Nicol, Dianne

    2017-01-01

    This chapter examines the ethical principles and governance frameworks for stem cell banks. Good governance of stem cell banks should balance facilitation of the clinical use of stem cells with the proper respect and protection of stem cell sample providers and stem cell recipients and ensure compliance with national regulatory requirements to foster public trust in the use of stem cell technology. Stem cell banks must develop with regard to the science, the needs of scientists, and the requirements of the public, which will benefit from this science. Given the international reach of this promising research and its clinical application, it is necessary for stem cell bank governance frameworks to be harmonized across jurisdictions.

  3. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  4. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  5. Can Stem Cell 'Patch' Help Heart Failure?

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_164475.html Can Stem Cell 'Patch' Help Heart Failure? Small improvement seen over ... Scientists report another step in the use of stem cells to help treat people with debilitating heart failure. ...

  6. Stem cell technology for neurodegenerative diseases.

    PubMed

    Lunn, J Simon; Sakowski, Stacey A; Hur, Junguk; Feldman, Eva L

    2011-09-01

    Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

  7. Early lymphocyte recovery at 28 d post-transplant is predictive of reduced risk of relapse in patients with acute myeloid leukemia transplanted with peripheral blood stem cell grafts.

    PubMed

    Michelis, Fotios V; Messner, Hans A; Loach, David; Uhm, Jieun; Gupta, Vikas; Lipton, Jeffrey H; Seftel, Matthew D; Kuruvilla, John; Kim, Dennis D

    2014-10-01

    Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for acute myeloid leukemia (AML). Impact of lymphocyte recovery on post-transplant outcomes has been suggested but reports are conflicting. We evaluated the impact of lymphocyte recovery at 28 d post-HCT in 191 AML patients using peripheral blood stem cells as graft. Patients were divided into those with absolute lymphocyte count (ALC) ≥ 0.5 × 10(9) /L (n = 111, 58%; high ALC group) and those with ALC < 0.5 × 10(9) /L (n = 80, 42%; low ALC group), at day 28 post-transplant. With a median follow-up of 49 months, overall survival (OS) was significantly improved in the high ALC group (59% at 3 yr) vs. patients with low ALC (40% at 3 yr, P = 0.03). Cumulative incidence of relapse (CIR) was significantly lower in the high ALC group (16% at 3 yr) vs. low ALC group (36% at 3 yr, P = 0.001). Multivariable analysis for CIR demonstrated high ALC group as an independent factor decreasing relapse risk (P = 0.03, HR = 0.49, 95% CI = 0.26-0.92). Multivariable analysis for OS and non-relapse mortality did not demonstrate ALC ≥ 0.5 × 10(9) /L at 28 d post-transplant to be predictive. We conclude that lymphocyte recovery with ALC ≥ 0.5 × 10(9) /L at day 28 post-transplant is associated with less relapse in AML patients undergoing allogeneic peripheral blood HCT, but without survival benefit.

  8. Iatrogenic limbal stem cell deficiency.

    PubMed Central

    Holland, E J; Schwartz, G S

    1997-01-01

    PURPOSE: To describe a group of patients with limbal stem cell (SC) deficiency without prior diagnosis of a specific disease entity known to be causative of SC deficiency. METHODS: We performed a retrospective review of the records of all patients with ocular surface disease presenting to the University of Minnesota between 1987 and 1996. Patients were categorized according to etiology of limbal deficiency. Patients who did not have a specific diagnosis previously described as being causative for limbal deficiency were analyzed. Risk factors, clinical findings and sequelae were evaluated. RESULTS: Eight eyes of six patients with stem cell deficiency not secondary to a known diagnosis were described. All eyes had prior ocular surgery involving the corneoscleral limbus. Six eyes had been on chronic topical medications and all eyes had concurrent external disease such as pterygium, keratoconjunctivitis sicca, rosacea or herpes simplex virus keratitis. All eyes had superior quadrants affected corresponding to areas of prior limbal surgery. Sequelae of disease included corneal scarring and neo-vascularization, and five eyes had with visual acuity of 20/200 or worse. CONCLUSIONS: Because the epitheliopathy started peripherally and extended centrally in all patients, we feel it represents a stem cell deficiency. The fact that all patients were affected superiorly, at sites of a prior limbal surgical incision, points to surgical trauma to the SC as the likely major etiologic factor for the deficiency. The surgical trauma to the limbal SC probably made these cells more susceptible to damage from other external disease influences and toxicity from chronic topical medications. Because the stem cell deficiency is secondary to prior ocular surgery and chronic topical medications, we propose the term "iatrogenic limbal stem cell deficiency". Images FIGURE 1 FIGURE 2A FIGURE 2B FIGURE 3A FIGURE 3B PMID:9440165

  9. Modeling Stem Cell Induction Processes

    PubMed Central

    Grácio, Filipe; Cabral, Joaquim; Tidor, Bruce

    2013-01-01

    Technology for converting human cells to pluripotent stem cell using induction processes has the potential to revolutionize regenerative medicine. However, the production of these so called iPS cells is still quite inefficient and may be dominated by stochastic effects. In this work we build mass-action models of the core regulatory elements controlling stem cell induction and maintenance. The models include not only the network of transcription factors NANOG, OCT4, SOX2, but also important epigenetic regulatory features of DNA methylation and histone modification. We show that the network topology reported in the literature is consistent with the observed experimental behavior of bistability and inducibility. Based on simulations of stem cell generation protocols, and in particular focusing on changes in epigenetic cellular states, we show that cooperative and independent reaction mechanisms have experimentally identifiable differences in the dynamics of reprogramming, and we analyze such differences and their biological basis. It had been argued that stochastic and elite models of stem cell generation represent distinct fundamental mechanisms. Work presented here suggests an alternative possibility that they represent differences in the amount of information we have about the distribution of cellular states before and during reprogramming protocols. We show further that unpredictability and variation in reprogramming decreases as the cell progresses along the induction process, and that identifiable groups of cells with elite-seeming behavior can come about by a stochastic process. Finally we show how different mechanisms and kinetic properties impact the prospects of improving the efficiency of iPS cell generation protocols. PMID:23667423

  10. [Genetic regulation of plant shoot stem cells].

    PubMed

    Al'bert, E V; Ezhova, T A

    2013-02-01

    This article describes the main features of plant stem cells and summarizes the results of studies of the genetic control of stem cell maintenance in the apical meristem of the shoot. It is demonstrated that the WUS-CLV gene system plays a key role in the maintenance of shoot apical stem cells and the formation of adventitious buds and somatic embryos. Unconventional concepts of plant stem cells are considered.

  11. Stem cells in kidney diseases.

    PubMed

    Soler, María José; José Tomas, Ortiz-Pérez

    2012-01-01

    Circulating bone marrow-derived endothelial progenitor cells (EPCs) seem to play a crucial role in both vasculogenesis and vascular homeostasis. Chronic kidney disease is a state of endothelial dysfunction, accelerated progression of atherosclerosis and high cardiovascular risk. As a consequence, cardiovascular disorders are the main cause of death in end-stage renal disease (ESRD). It has been shown that patients with advanced renal failure have decreased number of bone marrow-derived endothelial progenitor cells and impaired EPCs function. Moreover, in kidney transplant patients, renal graft function significantly correlated with EPC number. The reduced number of EPCs in patients with ESRD has been ascribed to the uremia. Therefore, therapies that improve the uremic status in dialysis patients such as nocturnal hemodialysis are associated with restoration of impaired EPCs number and migratory function. In fact, some of the common treatments for patients with chronic kidney disease such as erythropoietin, statins and angiotensin II receptor antagonist increase the number of EPCs. Nowadays, there is growing evidence indicating that, under pathophysiological conditions, stem cells (SCs) derived from bone marrow are able to migrate in the injured kidney, and they seem to play a role in glomerular and tubular regeneration. After acute tubular renal injury, surviving tubular epithelial cells and putative renal stem cells proliferate and differentiate into tubular epithelial cells to promote structural and functional repair. Moreover, bone marrow stem cells, including hematopoietic stem cells and mesenchymal stem cells can also participate in the repair process by proliferation and differentiation into renal lineages. For instance, mesenchymal SCs have been shown to decrease inflammation and enhance renal regeneration. The administration of ex vivo expanded bone marrow-derived mesenchymal SCs have been proved to be beneficial in various experimental models of acute

  12. An introduction to stem cell biology.

    PubMed

    Hemmat, Shirin; Lieberman, David M; Most, Sam P

    2010-10-01

    The field of stem cell biology has undergone tremendous expansion over the past two decades. Scientific investigation has continued to expand our understanding of these complex cells at a rapidly increasing rate. This understanding has produced a vast array of potential clinical applications. This article will serve as an overview of the current state of stem cell research as it applies to scientific and medical applications. Included in the discussion is a review of the many different types of stem cells, including but not limited to adult, embryonic, and perinatal stem cells. Also, this article describes somatic cell nuclear transfer, an exciting technology that allows the production of totipotent stem cells from fully differentiated cells, thereby eliminating the use of embryonic sources. This discussion should serve as a review of the field of stem cell biology and provide a foundation for the reader to better understand the interface of stem cell technology and facial plastic and reconstructive surgery.

  13. Stem/Progenitor cells in vascular regeneration.

    PubMed

    Zhang, Li; Xu, Qingbo

    2014-06-01

    A series of studies has been presented in the search for proof of circulating and resident vascular progenitor cells, which can differentiate into endothelial and smooth muscle cells and pericytes in animal and human studies. In terms of pluripotent stem cells, including embryonic stem cells, iPS, and partial-iPS cells, they display a great potential for vascular lineage differentiation. Development of stem cell therapy for treatment of vascular and ischemic diseases remains a major challenging research field. At the present, there is a clear expansion of research into mechanisms of stem cell differentiation into vascular lineages that are tested in animal models. Although there are several clinical trials ongoing that primarily focus on determining the benefits of stem cell transplantation in ischemic heart or peripheral ischemic tissues, intensive investigation for translational aspects of stem cell therapy would be needed. It is a hope that stem cell therapy for vascular diseases could be developed for clinic application in the future.

  14. Epidermal stem cells and their epigenetic regulation.

    PubMed

    Shen, Qi; Jin, Hongchuan; Wang, Xian

    2013-08-30

    Stem cells play an essential role in embryonic development, cell differentiation and tissue regeneration. Tissue homeostasis in adults is maintained by adult stem cells resident in the niches of different tissues. As one kind of adult stem cell, epidermal stem cells have the potential to generate diversified types of progeny cells in the skin. Although its biology is still largely unclarified, epidermal stem cells are widely used in stem cell research and regenerative medicine given its easy accessibility and pluripotency. Despite the same genome, cells within an organism have different fates due to the epigenetic regulation of gene expression. In this review, we will briefly discuss the current understanding of epigenetic modulation in epidermal stem cells.

  15. College Students' Conceptions of Stem Cells, Stem Cell Research, and Cloning

    ERIC Educational Resources Information Center

    Concannon, James P.; Siegel, Marcelle A.; Halverson, Kristy; Freyermuth, Sharyn

    2010-01-01

    In this study, we examined 96 undergraduate non-science majors' conceptions of stem cells, stem cell research, and cloning. This study was performed at a large, Midwest, research extensive university. Participants in the study were asked to answer 23 questions relating to stem cells, stem cell research, and cloning in an on-line assessment before…

  16. Stem cells and colorectal carcinogenesis

    PubMed Central

    Stoian, M; Stoica, V; Radulian, G

    2016-01-01

    Abstract Colorectal cancer represents an important cause of mortality and morbidity. Unfortunately, the physiopathology is still under study. There are theories about carcinogenesis and it is known that not only a single factor is responsible for the development of a tumor, but several conditions. Stem cells are a promising target for the treatment of colorectal cancer, along with the environment that has an important role. It has been postulated that mutations within the adult colonic stem cells may induce neoplastic changes. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumor and therefore they are responsible for recurrence. It is important to know that a new way of treatment needs to be found, since these cells are resistant to chemotherapy and radiotherapy. PMID:27713769

  17. [Cell transplant and regenerative stem cell therapy].

    PubMed

    Prosper, F

    2008-01-01

    The derivation of the first human embryonic stem cell lines as well as the notion of the unexpected plasticity and potential of the adult stem cells has significantly impacted the biomedical research. Many of the tissues long believe to lack any regenerative capacity has demonstrated otherwise. Patients alike physicians expectations for treatment of incurable diseases have also fuelled this field and in occasions have led to unrealistic expectations. In the next pages I review some of the tissue specific stem cells that have been used either in preclinical models or even in clinical research. Despite the effort of numerous investigators, more questions that answers remain in the field of cell therapy and only careful and independent -not biased- research will allow us to translate some of this findings into clinical application.

  18. Setting FIRES to Stem Cell Research

    ERIC Educational Resources Information Center

    Miller, Roxanne Grietz

    2005-01-01

    The goal of this lesson is to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. One of the challenges of discussing stem cell research is that the field is constantly evolving and the most current information changes almost daily. Few…

  19. Retinal stem cells and potential cell transplantation treatments.

    PubMed

    Lin, Tai-Chi; Hsu, Chih-Chien; Chien, Ke-Hung; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Chen, Shih-Jen

    2014-11-01

    The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone) and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells). The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  20. Haploidentical T Cell-Replete Transplantation with Post-Transplantation Cyclophosphamide for Patients in or above the Sixth Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an Human Leukocyte Antigen-Matched Related or Unrelated Donor.

    PubMed

    Blaise, Didier; Fürst, Sabine; Crocchiolo, Roberto; El-Cheikh, Jean; Granata, Angela; Harbi, Samia; Bouabdallah, Reda; Devillier, Raynier; Bramanti, Stephania; Lemarie, Claude; Picard, Christophe; Chabannon, Christian; Weiller, Pierre-Jean; Faucher, Catherine; Mohty, Bilal; Vey, Norbert; Castagna, Luca

    2016-01-01

    It has recently been shown that a T cell-replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD). All 3 groups were comparable, except for their conditioning. Patients in haplo-ID group received 2 days of post-transplantation high-dose cyclophosphamide followed by cyclosporine A and mycophenolate mofetil, whereas patients in other groups received pretransplantation antithymocyte globulin, cyclosporine A, and additional mycophenolate mofetil in case of 1-antigen mismatch. All patients but 1 in the haplo-ID group engrafted. The incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) was not statistically different between recipients from haplo-ID (cumulative incidence, 23%) and MRD (cumulative incidence, 21%) transplantations but it was lower than after UD HSCT (cumulative incidence, 44%). No patient in the haplo-ID group developed severe chronic GVHD, compared with cumulative incidences of 16% and 14% after MRD (P = .02) and UD (P = .03) grafts, respectively. The cumulative incidences of relapse were similar in the 3 groups, whereas nonrelapse mortality after UD HSCT was 3-fold higher than after haplo-ID or MRD HSCT. Overall, 2-year overall survival (70%), progression-free survival (67%), and progression and severe chronic GVHD-free survival (67%) probabilities after haplo-ID did not statistically differ from MRD transplantation (78%, 64%, and 51%, respectively), although they were higher than after UD transplantation (51% [P = .08], 38% [P = .02], and 31% [P = .007]). We conclude that T cell-replete haplo-ID HSCT followed by post-transplantation high

  1. Stem Cells for Neurovascular Repair in Stroke

    PubMed Central

    Shinozuka, Kazutaka; Dailey, Travis; Tajiri, Naoki; Ishikawa, Hiroto; Kim, Dae Won; Pabon, Mibel; Acosta, Sandra; Kaneko, Yuji; Borlongan, Cesar V

    2013-01-01

    Stem cells exert therapeutic effects against ischemic stroke via transplantation of exogenous stem cells or stimulation of endogenous stem cells within the neurogenic niches of subventricular zone and subgranular zone, or recruited from the bone marrow through peripheral circulation. In this paper, we review the different sources of stem cells that have been tested in animal models of stroke. In addition, we discuss specific mechanisms of action, in particular neurovascular repair by endothelial progenitor cells, as key translational research for advancing the clinical applications of stem cells for ischemic stroke. PMID:24077523

  2. Somatic stem cell biology and periodontal regeneration.

    PubMed

    Zhu, Bin; Liu, Yihan; Li, Dehua; Jin, Yan

    2013-01-01

    Somatic stem cells have been acknowledged for their ability to differentiate into multiple cell types and their capacity for self-renewal. Some mesenchymal stem cells play a dominant role in the repair and reconstruction of periodontal tissues. Both dental-derived and some non-dental-derived mesenchymal stem cells possess the capacity for periodontal regeneration under certain conditions with induced differentiation, proliferation, cellular secretion, and their interactions. Stem cell-based tissue engineering technology promises to bring improvements to periodontal regeneration, biologic tooth repair, and bioengineered implants. The present review discusses the roles and values of various somatic stem cells in periodontal regeneration.

  3. Cancer Stem Cells in Lung Tumorigenesis

    PubMed Central

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2011-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continued research in the field of lung cancer stem cell biology is vital, as ongoing efforts promise to yield new prognostic and therapeutic targets. PMID:20493987

  4. Notch signaling in cancer stem cells.

    PubMed

    Wang, Jialiang; Sullenger, Bruce A; Rich, Jeremy N

    2012-01-01

    Subpopulations of cancer cells with stem cell-like characteristics, termed cancer stem cells, have been identified in a wide range of human cancers. Cancer stem cells are defined by their ability to self-renew as well as recapitulate the original heterogeneity of cancer cells in culture and in serial xenotransplants. Not only are cancer stem cells highly tumorigenic, but these cells are implicated in tumor resistance to conventional chemotherapy and radiotherapy, thus highlighting their significance as therapeutic targets. Considerable similarities have been found between cancer stem cells and normal stem cells on their dependence on certain signaling pathways. More specifically, the core stem cell signaling pathways, such as the Wnt, Notch and Hedgehog pathways, also critically regulate the self-renewal and survival of cancer stem cells. While the oncogenic functions of Notch pathway have been well documented, its role in cancer stem cells is just emerging. In this chapter, we will discuss recent advances in cancer stem cell research and highlight the therapeutic potential of targeting Notch in cancer stem cells.

  5. Methods for Stem Cell Production and Therapy

    NASA Technical Reports Server (NTRS)

    Claudio, Pier Paolo (Inventor); Valluri, Jagan V. (Inventor)

    2015-01-01

    The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

  6. Nuclear Mechanics and Stem Cell Differentiation.

    PubMed

    Mao, Xinjian; Gavara, Nuria; Song, Guanbin

    2015-12-01

    Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

  7. Stem Cells in Prostate

    DTIC Science & Technology

    2005-03-01

    disease upon aging, specifically prostate cancer and benign prostatic hyperplasia . In order to study the cell differentiation lineage associated with...specifically prostate cancer and benign prostatic hyperplasia . In order to study the cell differentiation lineage associated with normal and diseased prostate

  8. Isolation and Characterization of Pluripotent Human Spermatogonial Stem Cell-Derived Cells

    PubMed Central

    Kossack, Nina; Meneses, Juanito; Shefi, Shai; Nguyen, Ha Nam; Chavez, Shawn; Nicholas, Cory; Gromoll, Joerg; Turek, Paul J; Reijo-Pera, Renee A

    2009-01-01

    Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells) from spermatogonial stem cells obtained from the adult mouse testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a testis biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus, and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8 weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming. PMID:18927477

  9. Stem cell strategies, future and beyond.

    PubMed

    Sugaya, Kiminobu

    2003-01-01

    The use of stem cells for neuroreplacement therapy is no longer science fiction--it is science fact. We have succeeded in the development of neural and mesenchymal stem cell transplantation to produce neural cells in the brain. We have seen the improvement of cognitive function in a memory-impaired aged animal model following stem cell transplantation. These results may promise a bright future for stem cell strategies. Before we begin to think about clinical applications beyond the present preclinical studies or even consider the pathophysiological environments of individual diseases, we must address and weigh the factors that may affect stem cell biology. Here, we not only show the potential for therapeutic applications for stem cell strategies in neuropathological conditions, but we also discuss the effects on the biology of stem cells of those factors that are altered under disease conditions.

  10. Endometrial stem cells in regenerative medicine.

    PubMed

    Verdi, Javad; Tan, Aaron; Shoae-Hassani, Alireza; Seifalian, Alexander M

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo.

  11. Minimal residual disease (MRD) status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL.

    PubMed

    Bader, P; Hancock, J; Kreyenberg, H; Goulden, N J; Niethammer, D; Oakhill, A; Steward, C G; Handgretinger, R; Beck, J F; Klingebiel, T

    2002-09-01

    We have retrospectively investigated the relationship between the level of minimal residual disease (MRD) detected in bone marrow taken prior to conditioning therapy and outcome following stem cell transplantation for high risk childhood ALL. Forty-one patients, in whom both a molecular marker of MRD and sufficient archival material was available, were included in the study. All were in remission at BMT: eight in CR1, 32 in CR2 and five in greater than CR2. MRD was measured by PCR amplification of antigen receptor gene rearrangements and clone-specific oligoprobing, the median sensitivity of detection being one leukaemic cell in 10000 normals. Results were classified as high-level positive (if a clonal band was evident after electrophoresis), low-level positive (if MRD was detected only after oligoprobing) and negative. MRD was detected at high levels in 17 patients, at low levels in 10 patients and 14 patients were MRD negative at the time of transplant. The 5-year event-free survival for these groups was 23%, 48% and 78%, respectively (P = 0.022). Limited multivariate analysis confirmed the significance of MRD (P = 0.0095) vs CR status, donor type, sex, immunophenotype and acute GvHD. This study confirms the strong relationship between MRD level and outcome following allogeneic transplantation. In contrast to a previous study we observed that a minority of children with high-level pre-BMT MRD can enter long lasting remission. The possible role for acute GVHD coupled with a graft-versus-leukaemia effect in the clearance of high level MRD in patients with ALL is discussed.

  12. Stem cells: are we ready for therapy?

    PubMed

    Schroeder, Insa S

    2014-01-01

    Cell therapy as a replacement for diseased or destroyed endogenous cells is a major component of regenerative medicine. Various types of stem cells are or will be used in clinical settings as autologous or allogeneic products. In this chapter, the progress that has been made to translate basic stem cell research into pharmaceutical manufacturing processes will be reviewed. Even if in public perception, embryonic stem (ES) cells and more recently induced pluripotent stem (iPS) cells dominate the field of regenerative medicine and will be discussed in great detail, it is the adult stem cells that are used for decades as therapeutics. Hence, these cells will be compared to ES and iPS cells. Finally, special emphasis will be placed on the scientific, technical, and economic challenges of developing stem cell-based in vitro model systems and cell therapies that can be commercialized.

  13. Challenges for heart disease stem cell therapy

    PubMed Central

    Hoover-Plow, Jane; Gong, Yanqing

    2012-01-01

    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. PMID:22399855

  14. Embryonic stem cell patents and human dignity.

    PubMed

    Resnik, David B

    2007-09-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells.

  15. Embryonic Stem Cell Patents and Human Dignity

    PubMed Central

    Resnik, David B.

    2009-01-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. PMID:17922198

  16. Stem cell maintenance in a different niche

    PubMed Central

    Ahn, Ji Yeon; Lee, Seung Tae

    2013-01-01

    To overcome the difficulty of controlling stem cell fate and function in applications to regenerative medicine, a number of alternative approaches have been made. Recent reports demonstrate that a non-cellular niche modulating the biophysical microenvironment with chemical factors can support stem cell self-renewal. In our previous studies, early establishment was executed to optimize biophysical factors and it was subsequently found that the microgeometry of the extracellular matrix made huge differences in stem cell behavior and phenotype. We review here a three-dimensional, non-cellular niche designed to support stem cell self-renewal. The characteristics of stem cells under the designed system are further discussed. PMID:23875159

  17. Magnetically Targeted Stem Cell Delivery for Regenerative Medicine

    PubMed Central

    Cores, Jhon; Caranasos, Thomas G.; Cheng, Ke

    2015-01-01

    Stem cells play a special role in the body as agents of self-renewal and auto-reparation for tissues and organs. Stem cell therapies represent a promising alternative strategy to regenerate damaged tissue when natural repairing and conventional pharmacological intervention fail to do so. A fundamental impediment for the evolution of stem cell therapies has been the difficulty of effectively targeting administered stem cells to the disease foci. Biocompatible magnetically responsive nanoparticles are being utilized for the targeted delivery of stem cells in order to enhance their retention in the desired treatment site. This noninvasive treatment-localization strategy has shown promising results and has the potential to mitigate the problem of poor long-term stem cell engraftment in a number of organ systems post-delivery. In addition, these same nanoparticles can be used to track and monitor the cells in vivo, using magnetic resonance imaging. In the present review we underline the principles of magnetic targeting for stem cell delivery, with a look at the logic behind magnetic nanoparticle systems, their manufacturing and design variants, and their applications in various pathological models. PMID:26133387

  18. Kidney stem cells in development, regeneration and cancer.

    PubMed

    Dziedzic, Klaudyna; Pleniceanu, Oren; Dekel, Benjamin

    2014-12-01

    The generation of nephrons during development depends on differentiation via a mesenchymal to epithelial transition (MET) of self-renewing, tissue-specific stem cells confined to a specific anatomic niche of the nephrogenic cortex. These cells may transform to generate oncogenic stem cells and drive pediatric renal cancer. Once nephron epithelia are formed the view of post-MET tissue renal growth and maintenance by adult tissue-specific epithelial stem cells becomes controversial. Recently, genetic lineage tracing that followed clonal evolution of single kidney cells showed that the need for new cells is constantly driven by fate-restricted unipotent clonal expansions in varying kidney segments arguing against a multipotent adult stem cell model. Lineage-restriction was similarly maintained in kidney organoids grown in culture. Importantly, kidney cells in which Wnt was activated were traced to give significant clonal progeny indicating a clonogenic hierarchy. In vivo nephron epithelia may be endowed with the capacity akin to that of unipotent epithelial stem/progenitor such that under specific stimuli can clonally expand/self renew by local proliferation of mature differentiated cells. Finding ways to ex vivo preserve and expand the observed in vivo kidney-forming capacity inherent to both the fetal and adult kidneys is crucial for taking renal regenerative medicine forward. Some of the strategies used to achieve this are sorting human fetal nephron stem/progenitor cells, growing adult nephrospheres or reprogramming differentiated kidney cells toward expandable renal progenitors.

  19. Mesenchymal stem cell exosomes.

    PubMed

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Lim, Sai Kiang

    2015-04-01

    MSCs are an extensively used cell type in clinical trials today. The initial rationale for their clinical testing was based on their differentiation potential. However, the lack of correlation between functional improvement and cell engraftment or differentiation at the site of injury has led to the proposal that MSCs exert their effects not through their differentiation potential but through their secreted product, more specifically, exosomes, a type of extracellular vesicle. We propose here that MSC exosomes function as an extension of MSC's biological role as tissue stromal support cells. Like their cell source, MSC exosomes help maintain tissue homeostasis for optimal tissue function. They target housekeeping biological processes that operate ubiquitously in all tissues and are critical in maintaining tissue homeostasis, enabling cells to recover critical cellular functions and begin repair and regeneration. This hypothesis provides a rationale for the therapeutic efficacy of MSCs and their secreted exosomes in a wide spectrum of diseases. Here, we give a brief introduction of the biogenesis of MSC exosomes, review their physiological functions and highlight some of their biochemical potential to illustrate how MSC exosomes could restore tissue homeostasis leading to tissue recovery and repair.

  20. Klotho, stem cells, and aging

    PubMed Central

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders. PMID:26346243

  1. Klotho, stem cells, and aging.

    PubMed

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.

  2. Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.

    PubMed

    Widmann, Thomas; Kneer, Harald; König, Jochem; Herrmann, Markus; Pfreundschuh, Michael

    2008-01-01

    Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells after triple stem cell transplantation with prolonged stem cell replication during the first year after stem cell transplantation.

  3. Plasticity of hematopoietic stem cells.

    PubMed

    Ogawa, Makio; LaRue, Amanda C; Mehrotra, Meenal

    2015-01-01

    Almost two decades ago, a number of cell culture and preclinical transplantation studies suggested the striking concept of the tissue-reconstituting ability of hematopoietic stem cells (HSCs). While this heralded an exciting time of radically new therapies for disorders of many organs and tissues, the concept was soon mired by controversy and remained dormant. This chapter provides a brief review of evidence for HSC plasticity including our findings based on single HSC transplantation in mouse. These studies strongly support the concept that HSCs are pluripotent and may be the source for the majority, if not all, of the cell types in our body.

  4. Clinical trials for stem cell therapies

    PubMed Central

    2011-01-01

    In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun. PMID:21569277

  5. Stem Cells News Update: A Personal Perspective

    PubMed Central

    Wong, SC

    2013-01-01

    This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy. PMID:24778557

  6. Stem cells news update: a personal perspective.

    PubMed

    Wong, Sc

    2013-12-01

    This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy.

  7. [Stem cells and tissue engineering techniques].

    PubMed

    Sica, Gigliola

    2013-01-01

    The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

  8. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-19

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

  9. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches

    PubMed Central

    Akram, Khondoker M.; Patel, Neil; Spiteri, Monica A.; Forsyth, Nicholas R.

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  10. Stem Cells, Science, and Public Reasoning

    ERIC Educational Resources Information Center

    Hurlbut, J. Benjamin; Robert, Jason Scott

    2012-01-01

    These are interesting days in the scientific, social, and political debates about human embryonic stem cell research. Pluripotent stem cells--cells that can, in principle, give rise to the body's full range of cell types--were previously derivable only from human embryos that were destroyed in the process. Now, a variety of somatic cell types can…

  11. Stem cells, mitochondria and aging.

    PubMed

    Ahlqvist, Kati J; Suomalainen, Anu; Hämäläinen, Riikka H

    2015-11-01

    Decline in metabolism and regenerative potential of tissues are common characteristics of aging. Regeneration is maintained by somatic stem cells (SSCs), which require tightly controlled energy metabolism and genomic integrity for their homeostasis. Recent data indicate that mitochondrial dysfunction may compromise this homeostasis, and thereby contribute to tissue degeneration and aging. Progeroid Mutator mouse, accumulating random mtDNA point mutations in their SSCs, showed disturbed SSC homeostasis, emphasizing the importance of mtDNA integrity for stem cells. The mechanism involved changes in cellular redox-environment, including subtle increase in reactive oxygen species (H₂O₂and superoxide anion), which did not cause oxidative damage, but disrupted SSC function. Mitochondrial metabolism appears therefore to be an important regulator of SSC fate determination, and defects in it in SSCs may underlie premature aging. Here we review the current knowledge of mitochondrial contribution to SSC dysfunction and aging. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.

  12. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  13. Effects of nanotopography on stem cell phenotypes

    PubMed Central

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

    2009-01-01

    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. PMID:21607108

  14. Stem cell directed gene therapy.

    PubMed

    Engel, B C; Kohn, D B

    1999-05-01

    A potential therapeutic approach to HIV-1 infection is the genetic modification of cells of a patient to make them resistant to HIV-1. Hematopoietic stem cells are an attractive target for gene therapy of AIDS because of their ability to generate a broad repertoire of mature T lymphocytes, as well as the monocytic cells (macrophages, dendritic cells and microglia) which are also involved in HIV-1 pathogenesis. A number of synthetic "anti-HIV-1 genes" have been developed which inhibit HIV-1 replication. However, current methods for gene transfer into human hematopoietic stem cells, using retroviral vectors derived from the Moloney murine leukemia virus, have been minimally effective. Clinical trials performed to date in which hematopoietic cells from HIV-1-positive patients have been transduced with retroviral vectors and then reinfused have produced low to undetectable levels of gene-containing peripheral blood leukocytes. New vector delivery systems, such as lentiviral vectors, need to be developed to ensure efficient gene transfer and persistent transgene expression to provide life-long resistance to the cells targeted by HIV-1.

  15. Cancer stem cells and metastasis.

    PubMed

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

    Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

  16. Embryonic stem cells: testing the germ-cell theory.

    PubMed

    Hochedlinger, Konrad

    2011-10-25

    The exact cellular origin of embryonic stem cells remains elusive. Now a new study provides compelling evidence that embryonic stem cells, established under conventional culture conditions, originate from a transient germ-cell state.

  17. Haematopoietic stem cells: past, present and future

    PubMed Central

    Ng, Ashley P; Alexander, Warren S

    2017-01-01

    The discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as a source of haematopoietic cells capable of protecting an organism from otherwise lethal irradiation led to the intense search for their identity and characteristics. Using functional assays along with evolving techniques for isolation of haematopoietic cells, haematopoietic stem cell populations were able to be enriched and their characteristics analysed. The key haematopoietic stem cell characteristics of pluripotentiality and the ability for self-renewal have emerged as characteristics of several haematopoietic stem cell populations, including those that have recently challenged the conventional concepts of the haematopoietic hierarchy. Human allogeneic stem cell therapy relies on these functional characteristics of haematopoietic stem cells that can be isolated from peripheral blood, bone marrow or cord blood, with the additional requirement that immunological barriers need to be overcome to allow sustained engraftment while minimising risk of graft-versus-host disease developing in the recipient of transplanted stem cells. Current and future research will continue to focus on the identification of haematopoietic stem cell regulators and methods for in vitro and in vivo stem cell manipulation, including genome editing, to expand the scope, potential and safety of therapy using haematopoietic stem cells. PMID:28180000

  18. Making new beta cells from stem cells.

    PubMed

    Colman, Alan

    2004-06-01

    In 2000, Shapiro et al. provided compelling "proof of principle" data showing that the transplantation of human islets, purified from cadaveric material, could restore severely diabetic, Type 1 patients to insulin independence. This demonstration prompted renewed efforts to find an alternative and sustainable source of surrogate islet cells for cell therapy. Experiments involving adult ductal and liver "stem" cells, or embryonic stem cells, are prominent amongst these endeavors and are reviewed in this article. Whilst there are many published claims to success in converting ES cells into insulin secreting, glucose responsive cells, all require careful reinterpretation in the light of findings that cells can adsorb insulin present in growth media. It is likely that work with adult cells is less prone to this potential artifact and significant progress has been made in producing insulin-secreting cells. Assessment of in vivo function in the surrogate cells is most frequently made using cell transplantation into toxin-induced, diabetic mice, but this model is rarely used to maximal advantage. In many cases, it remains unclear whether reductions in the hyperglycemia result from insulin secretion from the transplanted cells or are due to recovery of endogenous islet function. In this latter context, experiments are reviewed where endogenous stimulation of recovery is engendered even by irradiated donor cells.

  19. Breast Cancer Stem Cells in Antiestrogen Resistance

    DTIC Science & Technology

    2013-08-01

    stimulated by antiestrogens. The effects of antiestrogens on the ER-positive breast cancer stem/progenitor involve changes of both proliferation and...self-renewal capabilities of breast cancer stem/progenitor cells. The effects of antiestrogens on the ER- positive breast cancer stem/progenitor...potent tumor-seeding efficiency. . Fig 3. The effects of antiestrogens on the differentiation of ER-positive breast cancer stem cells expressing

  20. Stem Cells in the Nervous System

    PubMed Central

    Maldonado-Soto, Angel R.; Oakley, Derek H.; Wichterle, Hynek; Stein, Joel; Doetsch, Fiona K.; Henderson, Christopher E.

    2014-01-01

    Given their capacity to regenerate cells lost through injury or disease, stem cells offer new vistas into possible treatments for degenerative diseases and their underlying causes. As such, stem cell biology is emerging as a driving force behind many studies in the field of regenerative medicine. This review focuses on our current understanding of the applications of stem cells in treating ailments of the human brain, with an emphasis on neurodegenerative diseases. Two types of neural stem cells are discussed: endogenous neural stem cells residing within the adult brain, and pluripotent stem cells capable of forming neural cells in culture. Endogenous neural stem cells give rise to neurons throughout life, but they are restricted to specialized regions in the brain. Elucidating the molecular mechanisms regulating these cells is key in determining their therapeutic potential, as well as finding mechanisms to activate dormant stem cells outside of these specialized microdomains. In parallel, patient-derived stem cells can be used to generate neural cells in culture, providing new tools for disease modeling, drug testing and cell-based therapies. Turning these technologies into viable treatments will require the integration of basic science with clinical skills in rehabilitation. PMID:24800720

  1. Engineering Stem Cells for Biomedical Applications.

    PubMed

    Yin, Perry T; Han, Edward; Lee, Ki-Bum

    2016-01-07

    Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer.

  2. Reforming craniofacial orthodontics via stem cells.

    PubMed

    Mohanty, Pritam; Prasad, N K K; Sahoo, Nivedita; Kumar, Gunjan; Mohanty, Debapreeti; Sah, Sushila

    2015-01-01

    Stem cells are the most interesting cells in cell biology. They have the potential to evolve as one of the most powerful technologies in the future. The future refers to an age where it will be used extensively in various fields of medical and dental sciences. Researchers have discovered a number of sources from which stem cells can be derived. Craniofacial problems are very common and occur at all ages. Stem cells can be used therapeutically in almost every field of health science. In fact, many procedures will be reformed after stem cells come into play. This article is an insight into the review of the current researches being carried out on stem cells and its use in the field of orthodontics, which is a specialized branch of dentistry. Although the future is uncertain, there is a great possibility that stem cells will be used extensively in almost all major procedures of orthodontics.

  3. Lung stem cell update: promise and controversy.

    PubMed

    Neuringer, I P; Randell, S H

    2006-03-01

    Currently, there is great enthusiasm about potential stem cell therapies for intractable diseases. We previously reviewed the topic of stem cells in lung injury and repair, including the role of endogenous, tissue (somatic) stem cells and the contribution of circulating cells to the lung parenchyma. Our purpose here is to provide a concise update in this fast-moving field. New information and ongoing debate focus attention on basic issues in lung stem cell biology and highlight the need for additional studies to establish the feasibility of cell therapies to prevent or treat lung diseases.

  4. Stem Cells for Augmenting Tendon Repair

    PubMed Central

    Gulotta, Lawrence V.; Chaudhury, Salma; Wiznia, Daniel

    2012-01-01

    Tendon healing is fraught with complications such as reruptures and adhesion formation due to the formation of scar tissue at the injury site as opposed to the regeneration of native tissue. Stem cells are an attractive option in developing cell-based therapies to improve tendon healing. However, several questions remain to be answered before stem cells can be used clinically. Specifically, the type of stem cell, the amount of cells, and the proper combination of growth factors or mechanical stimuli to induce differentiation all remain to be seen. This paper outlines the current literature on the use of stem cells for tendon augmentation. PMID:22190960

  5. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    SciTech Connect

    Varga, Nora; Vereb, Zoltan; Rajnavoelgyi, Eva; Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs; Apati, Agota

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  6. Stem Cells in the Cornea

    PubMed Central

    Hertsenberg, Andrew J.; Funderburgh, James L.

    2017-01-01

    The cornea is the tough, transparent tissue through which light first enters the eye and functions as a barrier to debris and infection as well as two-thirds of the refractive power of the eye. Corneal damage that is not promptly treated will often lead to scarring and vision impairment. Due to the limited options currently available to treat corneal scars, the identification and isolation of stem cells in the cornea has received much attention, as they may have potential for autologous, cell-based approaches to the treatment of damaged corneal tissue. PMID:26310147

  7. What Is a Blood and Marrow Stem Cell Transplant?

    MedlinePlus

    ... and Bone Marrow Transplant Also known as hematopoietic stem cell transplant, hematopoietic cell transplant, autologous transplant, or allogeneic ... or bone marrow transplant replaces abnormal blood-forming stem cells with healthy cells. When the healthy stem cells ...

  8. PEDF & stem cells: niche vs. nurture.

    PubMed

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

    2014-01-01

    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.

  9. Mesenchymal dental stem cells in regenerative dentistry.

    PubMed

    Rodríguez-Lozano, Francisco-Javier; Insausti, Carmen-Luisa; Iniesta, Francisca; Blanquer, Miguel; Ramírez, María-del-Carmen; Meseguer, Luis; Meseguer-Henarejos, Ana-Belén; Marín, Noemí; Martínez, Salvador; Moraleda, José-María

    2012-11-01

    In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in the known of growth factors and signalling molecules implicated in tooth development and regeneration of different structures of teeth. Furthermore, these cells need a fabulous scaffold that facility their integration, differentiation, matrix synthesis and promote multiple specific interactions between cells. In this review, we give a brief description of tooth development and anatomy, definition and classification of stem cells, with special attention of mesenchymal stem cells, commonly used in the cellular therapy for their trasdifferentiation ability, non ethical problems and acceptable results in preliminary clinical trials. In terms of tissue engineering, we provide an overview of different types of mesenchymal stem cells that have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs), growth factors implicated in regeneration teeth and types of scaffolds for dental tissue regeneration.

  10. Induced Pluripotent Stem Cells: Characteristics and Perspectives

    NASA Astrophysics Data System (ADS)

    Cantz, Tobias; Martin, Ulrich

    The induction of pluripotency in somatic cells is widely considered as a major breakthrough in regenerative medicine, because this approach provides the basis for individualized stem cell-based therapies. Moreover, with respect to cell transplantation and tissue engineering, expertise from bioengineering to transplantation medicine is now meeting basic research of stem cell biology.

  11. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    DTIC Science & Technology

    2015-07-01

    stem cells (CSCs)- stem cell like cells in tumors that have stem cell properties and tumor initiating ability- retain epigenetic memories of their...months showing megacephaly. Abb: ctx=cortex, cb= cerebellum, hp= hippocampus Page 5 of 12 To circumvent early lethality associated with PIK3CA

  12. Mammary stem cells have myoepithelial cell properties

    PubMed Central

    Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  13. Establishment of a Mesenchymal Stem Cell Bank

    PubMed Central

    Cooper, Khushnuma; Viswanathan, Chandra

    2011-01-01

    Adult stem cells have generated great amount of interest amongst the scientific community for their potential therapeutic applications for unmet medical needs. We have demonstrated the plasticity of mesenchymal stem cells isolated from the umbilical cord matrix. Their immunological profile makes it even more interesting. We have demonstrated that the umbilical cord is an inexhaustible source of mesenchymal stem cells. Being a very rich source, instead of discarding this tissue, we worked on banking these cells for regenerative medicine application for future use. The present paper gives a detailed account of our experience in the establishment of a mesenchymal stem cell bank at our facility. PMID:21826152

  14. Pancreatic cancer stem cells: fact or fiction?

    PubMed

    Bhagwandin, Vikash J; Shay, Jerry W

    2009-04-01

    The terms cancer-initiating or cancer stem cells have been the subject of great interest in recent years. In this review we will use pancreatic cancer as an overall theme to draw parallels with historical findings to compare to recent reports of stem-like characteristics in pancreatic cancer. We will cover such topics as label-retaining cells (side-population), ABC transporter pumps, telomerase, quiescence, cell surface stem cell markers, and epithelial-mesenchymal transitions. Finally we will integrate the available findings into a pancreatic stem cell model that also includes metastatic disease.

  15. Un(MaSC)ing Stem Cell Dynamics in Mammary Branching Morphogenesis.

    PubMed

    Greenwood, Erin; Wrenn, Emma D; Cheung, Kevin J

    2017-02-27

    The properties of stem cells that participate in mammary gland branching morphogenesis remain contested. Reporting in Nature, Scheele et al. (2017) establish a model for post-pubertal mammary branching morphogenesis in which position-dependent, lineage-restricted stem cells undergo cell mixing in order to contribute to long-term growth.

  16. Effect of aging on stem cells

    PubMed Central

    Ahmed, Abu Shufian Ishtiaq; Sheng, Matilda HC; Wasnik, Samiksha; Baylink, David J; Lau, Kin-Hing William

    2017-01-01

    Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of aging-associated disorders, but also in future development of novel effective stem cell-based therapies to treat aging-associated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects. PMID:28261550

  17. Patenting human genes and stem cells.

    PubMed

    Martin-Rendon, Enca; Blake, Derek J

    2007-01-01

    Cell lines and genetically modified single cell organisms have been considered patentable subjects for the last two decades. However, despite the technical patentability of genes and stem cell lines, social and legal controversy concerning their 'ownership' has surrounded stem cell research in recent years. Some granted patents on stem cells with extremely broad claims are casting a shadow over the commercialization of these cells as therapeutics. However, in spite of those early patents, the number of patent applications related to stem cells is growing exponentially. Both embryonic and adult stem cells have the ability to differentiate into several cell lineages in an organism as a result of specific genetic programs that direct their commitment and cell fate. Genes that control the pluripotency of stem cells have been recently identified and the genetic manipulation of these cells is becoming more efficient with the advance of new technologies. This review summarizes some of the recent published patents on pluripotency genes, gene transfer into stem cells and genetic reprogramming and takes the hematopoietic and embryonic stem cell as model systems.

  18. Stem cell niche engineering through droplet microfluidics.

    PubMed

    Allazetta, Simone; Lutolf, Matthias P

    2015-12-01

    Stem cells reside in complex niches in which their behaviour is tightly regulated by various biochemical and biophysical signals. In order to unveil some of the crucial stem cell-niche interactions and expedite the implementation of stem cells in clinical and pharmaceutical applications, in vitro methodologies are being developed to reconstruct key features of stem cell niches. Recently, droplet-based microfluidics has emerged as a promising strategy to build stem cell niche models in a miniaturized and highly precise fashion. This review highlights current advances in using droplet microfluidics in stem cell biology. We also discuss recent efforts in which microgel technology has been interfaced with high-throughput analyses to engender screening paradigms with an unparalleled potential for basic and applied biological studies.

  19. Stem cells in the light of evolution

    PubMed Central

    Chakraborty, Chiranjib; Agoramoorthy, Govindasamy

    2012-01-01

    All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells. PMID:22825600

  20. Of Microenvironments and Mammary Stem Cells

    SciTech Connect

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  1. Stem cells and bone diseases: new tools, new perspective.

    PubMed

    Riminucci, Mara; Remoli, Cristina; Robey, Pamela G; Bianco, Paolo

    2015-01-01

    Postnatal skeletal stem cells are a unique class of progenitors with biological properties that extend well beyond the limits of stemness as commonly defined. Skeletal stem cells sustain skeletal tissue homeostasis, organize and maintain the complex architectural structure of the bone marrow microenvironment and provide a niche for hematopoietic progenitor cells. The identification of stem cells in the human post-natal skeleton has profoundly changed our approach to the physiology and pathology of this system. Skeletal diseases have been long interpreted essentially in terms of defective function of differentiated cells and/or abnormal turnover of the matrix that they produce. The notion of a skeletal stem cell has brought forth multiple, novel concepts in skeletal biology that provide potential alternative concepts. At the same time, the recognition of the complex functions played by skeletal progenitors, such as the structural and functional organization of the bone marrow, has provided an innovative, unifying perspective for understanding bone and bone marrow changes simultaneously occurring in many disorders. Finally, the possibility to isolate and highly enrich for skeletal progenitors, enables us to reproduce perfectly normal or pathological organ miniatures. These, in turn, provide suitable models to investigate and manipulate the pathogenetic mechanisms of many genetic and non-genetic skeletal diseases. This article is part of a Special Issue entitled Stem cells and Bone.

  2. [Bioethical challenges of stem cell tourism].

    PubMed

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

    2013-08-01

    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.

  3. Stem cells: classifications, controversies, and clinical applications.

    PubMed

    Fortier, Lisa A

    2005-01-01

    The application of stem cells in regenerative and reparative therapies is emerging in surgery. Published information can lead to an over simplified view of stem cells with respect to their definitions, tissues of origin, abilities to differentiate into tissue lineages, and their capacity for functional tissue regeneration. The goals of this review article are to define embryonic and adult stem cells, compare differences between them, and summarize their potential clinical applications.

  4. Programming Retinal Stem Cells into Cone Photoreceptors

    DTIC Science & Technology

    2015-12-01

    to program human stem cells directly into cones. Using RNA -seq, we identified several genes that are upregulated in advance of the earliest...reverse vision loss. 15. SUBJECT TERMS Cone photoreceptor, retina, retinal stem cell, Otx2, Onecut1, Blimp1, RNA -seq., transcription factors, and...1 Keywords: 1. Cone photoreceptor 2. Retina 3. Retinal stem cell 4. Otx2 5. Onecut1 6. Blimp1 7. RNA -seq. 8. Transcription factors 9

  5. Telomeres, stem cells, and hematology

    PubMed Central

    2008-01-01

    Telomeres are highly dynamic structures that adjust the cellular response to stress and growth stimulation based on previous cell divisions. This critical function is accomplished by progressive telomere shortening and DNA damage responses activated by chromosome ends without sufficient telomere repeats. Repair of critically short telomeres by telomerase or recombination is limited in most somatic cells, and apoptosis or cellular senescence is triggered when too many uncapped telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germ line that typically express high levels of telomerase. In somatic cells, the telomere length typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Loss of (stem) cells via telomere attrition provides strong selection for abnormal cells in which malignant progression is facilitated by genome instability resulting from uncapped telomeres. The critical role of telomeres in cell proliferation and aging is illustrated in patients with 50% of normal telomerase levels resulting from a mutation in one of the telomerase genes. Here, the role of telomeres and telomerase in human biology is reviewed from a personal historical perspective. PMID:18263784

  6. Stem cell reprogramming: A 3D boost

    NASA Astrophysics Data System (ADS)

    Abilez, Oscar J.; Wu, Joseph C.

    2016-03-01

    Biophysical factors in an optimized three-dimensional microenvironment enhance the reprogramming efficiency of human somatic cells into pluripotent stem cells when compared to traditional cell-culture substrates.

  7. Ocular stem cells: a status update!

    PubMed Central

    2014-01-01

    Stem cells are unspecialized cells that have been a major focus of the field of regenerative medicine, opening new frontiers and regarded as the future of medicine. The ophthalmology branch of the medical sciences was the first to directly benefit from stem cells for regenerative treatment. The success stories of regenerative medicine in ophthalmology can be attributed to its accessibility, ease of follow-up and the eye being an immune-privileged organ. Cell-based therapies using stem cells from the ciliary body, iris and sclera are still in animal experimental stages but show potential for replacing degenerated photoreceptors. Limbal, corneal and conjunctival stem cells are still limited for use only for surface reconstruction, although they might have potential beyond this. Iris pigment epithelial, ciliary body epithelial and choroidal epithelial stem cells in laboratory studies have shown some promise for retinal or neural tissue replacement. Trabecular meshwork, orbital and sclera stem cells have properties identical to cells of mesenchymal origin but their potential has yet to be experimentally determined and validated. Retinal and retinal pigment epithelium stem cells remain the most sought out stem cells for curing retinal degenerative disorders, although treatments using them have resulted in variable outcomes. The functional aspects of the therapeutic application of lenticular stem cells are not known and need further attention. Recently, embryonic stem cell-derived retinal pigment epithelium has been used for treating patients with Stargardts disease and age-related macular degeneration. Overall, the different stem cells residing in different components of the eye have shown some success in clinical and animal studies in the field of regenerative medicine. PMID:25158127

  8. Plant stem cells as innovation in cosmetics.

    PubMed

    Moruś, Martyna; Baran, Monika; Rost-Roszkowska, Magdalena; Skotnicka-Graca, Urszula

    2014-01-01

    The stem cells thanks to their ability of unlimited division number or transformation into different cell types creating organs, are responsible for regeneration processes. Depending on the organism in which the stem cells exists, they divide to the plant or animal ones. The later group includes the stem cells existing in both embryo's and adult human's organs. It includes, among others, epidermal stem cells, located in the hair follicle relieves and also in its basal layers, and responsible for permanent regeneration of the epidermis. Temporary science looks for method suitable for stimulation of the epidermis stem cells, amongst the other by delivery of e.g., growth factors for proliferation that decrease with the age. One of the methods is the use of the plant cell culture technology, including a number of methods that should ensure growth of plant cells, issues or organs in the environment with the microorganism-free medium. It uses abilities of the different plant cells to dedifferentiation into stem cells and coming back to the pluripotent status. The extracts obtained this way from the plant stem cells are currently used for production of both common or professional care cosmetics. This work describes exactly impact of the plant stem cell extract, coming from one type of the common apple tree (Uttwiler Spätlauber) to human skin as one of the first plant sorts, which are used in cosmetology and esthetic dermatology.

  9. Alternative splicing modulates stem cell differentiation.

    PubMed

    Fu, Ru-Huei; Liu, Shih-Ping; Ou, Chen-Wei; Yu, Hsiu-Hui; Li, Kuo-Wei; Tsai, Chang-Hai; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2009-01-01

    Stem cells have the surprising potential to develop into many different cell types. Therefore, major research efforts have focused on transplantation of stem cells and/or derived progenitors for restoring depleted diseased cells in degenerative disorders. Understanding the molecular controls, including alternative splicing, that arise during lineage differentiation of stem cells is crucial for developing stem cell therapeutic approaches in regeneration medicine. Alternative splicing to allow a single gene to encode multiple transcripts with different protein coding sequences and RNA regulatory elements increases genomic complexities. Utilizing differences in alternative splicing as a molecular marker may be more sensitive than simply gene expression in various degrees of stem cell differentiation. Moreover, alternative splicing maybe provide a new concept to acquire induced pluripotent stem cells or promote cell-cell transdifferentiation for restorative therapies and basic medicine researches. In this review, we highlight the recent advances of alternative splicing regulation in stem cells and their progenitors. It will hopefully provide much needed knowledge into realizing stem cell biology and related applications.

  10. Mesenchymal stem cells, aging and regenerative medicine

    PubMed Central

    Raggi, Chiara; Berardi, Anna C.

    2012-01-01

    Summary Tissue maintenance and regeneration is dependent on stem cells and increasing evidence has shown to decline with age. Stem cell based-aging is thought to influence therapeutic efficacy. Mesenchymal stromal cells (MSCs) are involved in tissue regeneration. Here, we discuss the effects of age-related changes on MSC properties considering their possible use in research or regenerative medicine. PMID:23738303

  11. Nanomaterials for Engineering Stem Cell Responses.

    PubMed

    Kerativitayanan, Punyavee; Carrow, James K; Gaharwar, Akhilesh K

    2015-08-05

    Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial-stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial-stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications.

  12. Stomach development, stem cells and disease.

    PubMed

    Kim, Tae-Hee; Shivdasani, Ramesh A

    2016-02-15

    The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms.

  13. Paediatric idiopathic limbal stem cell deficiency.

    PubMed

    Vincent, Stephen J; Lee, Graham A

    2017-03-20

    Acquired limbal stem cell deficiency (LSCD) describes a condition in which the corneal limbal stem cells are altered or destroyed, typically due to ocular trauma, chronic allergy or inflammation. Idiopathic LSCD is a term used to describe limbal stem cell failure in the absence of any identifiable causative factor. While several cases of adult-onset LSCD have been identified previously, this case report describes a rare presentation of bilateral asymmetric idiopathic paediatric limbal stem cell deficiency in a sixteen-year-old male with an otherwise unremarkable ocular history.

  14. Wnt Signaling in Cancer Stem Cell Biology

    PubMed Central

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  15. Genetic and epigenetic instability of stem cells.

    PubMed

    Rajamani, Karthyayani; Li, Yuan-Sheng; Hsieh, Dean-Kuo; Lin, Shinn-Zong; Harn, Horng-Jyh; Chiou, Tzyy-Wen

    2014-01-01

    Recently, research on stem cells has been receiving an increasing amount of attention, both for its advantages and disadvantages. Genetic and epigenetic instabilities among stem cells have been a recurring obstacle to progress in regenerative medicine using stem cells. Various reports have stated that these instabilities can transform stem cells when transferred in vivo and thus have the potential to develop tumors. Previous research has shown that various extrinsic and intrinsic factors can contribute to the stability of stem cells. The extrinsic factors include growth supplements, growth factors, oxygen tension, passage technique, and cryopreservation. Controlling these factors based on previous reports may assist researchers in developing strategies for the production and clinical application of "safe" stem cells. On the other hand, the intrinsic factors can be unpredictable and uncontrollable; therefore, to ensure the successful use of stem cells in regenerative medicine, it is imperative to develop and implement appropriate strategies and technique for culturing stem cells and to confirm the genetic and epigenetic safety of these stem cells before employing them in clinical trials.

  16. Pituitary stem cells: where do we stand?

    PubMed

    Vankelecom, Hugo; Chen, Jianghai

    2014-03-25

    Some 5 years ago, the stem cells of the adult pituitary gland were discovered. Subsequent in-depth characterization revealed expression of several stemness markers and embryo-typical factors. Now, the quest is open to decipher their role in the gland. When and how pituitary stem cells differentiate to contribute to the mature hormone-producing cell populations is not known. New research models support their involvement in cell regeneration after injury in the gland, and suggest a possible role in pituitary tumor formation. From their expression phenotype, pituitary stem cells seem to re-use embryonic developmental programs during the creation of new hormonal cells. Here, we will review the latest progression in the domain of pituitary stem cells, including the uncovering of some new molecular flavors and of the first potential functions. Eventually, we will speculate on their differentiation programs towards hormonal cells, with a particular focus on gonadotropes.

  17. Dental Pulp Stem Cells Differentiation Reveals New Insights in Oct4A Dynamics

    PubMed Central

    D'Aurizio, Federica; Puppato, Elisa; Pandolfi, Maura; Beltrami, Antonio Paolo; Cesselli, Daniela; Falini, Giuseppe; Beltrami, Carlo Alberto; Curcio, Francesco

    2012-01-01

    Although the role played by the core transcription factor network, which includes c-Myc, Klf4, Nanog, and Oct4, in the maintenance of embryonic stem cell (ES) pluripotency and in the reprogramming of adult cells is well established, its persistence and function in adult stem cells are still debated. To verify its persistence and clarify the role played by these molecules in adult stem cell function, we investigated the expression pattern of embryonic and adult stem cell markers in undifferentiated and fully differentiated dental pulp stem cells (DPSC). A particular attention was devoted to the expression pattern and intracellular localization of the stemness-associated isoform A of Oct4 (Oct4A). Our data demonstrate that: Oct4, Nanog, Klf4 and c-Myc are expressed in adult stem cells and, with the exception of c-Myc, they are significantly down-regulated following differentiation. Cell differentiation was also associated with a significant reduction in the fraction of DPSC expressing the stem cell markers CD10, CD29 and CD117. Moreover, a nuclear to cytoplasm shuttling of Oct4A was identified in differentiated cells, which was associated with Oct4A phosphorylation. The present study would highlight the importance of the post-translational modifications in DPSC stemness maintenance, by which stem cells balance self-renewal versus differentiation. Understanding and controlling these mechanisms may be of great importance for stemness maintenance and stem cells clinical use, as well as for cancer research. PMID:22844522

  18. Current Biosafety Considerations in Stem Cell Therapy

    PubMed Central

    Mousavinejad, Masoumeh; Andrews, Peter W.; Shoraki, Elham Kargar

    2016-01-01

    Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient’s life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies. PMID:27540533

  19. Lineage tracing quantification reveals symmetric stem cell division in Drosophila male germline stem cells.

    PubMed

    Salzmann, Viktoria; Inaba, Mayu; Cheng, Jun; Yamashita, Yukiko M

    2013-12-01

    In the homeostatic state, adult stem cells divide either symmetrically to increase the stem cell number to compensate stem cell loss, or asymmetrically to maintain the population while producing differentiated cells. We have investigated the mode of stem cell division in the testes of Drosophila melanogaster by lineage tracing and confirm the presence of symmetric stem cell division in this system. We found that the rate of symmetric division is limited to 1-2% of total germline stem cell (GSC) divisions, but it increases with expression of a cell adhesion molecule, E-cadherin, or a regulator of the actin cytoskeleton, Moesin, which may modulate adhesiveness of germ cells to the stem cell niche. Our results indicate that the decision regarding asymmetric vs. symmetric division is a dynamically regulated process that contributes to tissue homeostasis, responding to the needs of the tissue.

  20. Single-cell sequencing in stem cell biology.

    PubMed

    Wen, Lu; Tang, Fuchou

    2016-04-15

    Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

  1. Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging.

    PubMed

    Asumda, Faizal Z

    2013-05-14

    Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient's own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging.

  2. Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging

    PubMed Central

    2013-01-01

    Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient’s own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging. PMID:23673056

  3. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    PubMed

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

  4. Nonclinical safety strategies for stem cell therapies

    SciTech Connect

    Sharpe, Michaela E.; Morton, Daniel; Rossi, Annamaria

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  5. Cancer stem cells in glioblastoma

    PubMed Central

    Lathia, Justin D.; Mack, Stephen C.; Mulkearns-Hubert, Erin E.; Valentim, Claudia L.L.; Rich, Jeremy N.

    2015-01-01

    Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial. PMID:26109046

  6. Enhancing spontaneous stem cell healing (Review)

    PubMed Central

    MAGUIRE, GREG; FRIEDMAN, PETER

    2014-01-01

    Adult stem cells are distributed throughout the human body and are responsible to a great extent for the body’s ability to maintain and heal itself. Accumulating data since the 1990s regarding stem cells have demonstrated that the beneficial effects of stem cells are not restricted to their ability to differentiate and are more likely due to their ability to release a multitude of molecules. Recent studies indicated that ≤80% of the therapeutic benefit of adult stem cells is manifested by the stem cell released molecules (SRM) rather than the differentiation of the stem cells into mature tissue. Stem cells may release potent combinations of factors that modulate the molecular composition of the cellular milieu to evoke a multitude of responses from neighboring cells. A multitude of pathways are involved in cellular and tissue function and, when the body is in a state of disease or trauma, a multitude of pathways are involved in the underlying mechanisms of that disease or trauma. Therefore, stem cells represent a natural systems-based biological factory for the production and release of a multitude of molecules that interact with the system of biomolecular circuits underlying disease or tissue damage. Currently, efforts are aimed at defining, stimulating, enhancing and harnessing SRM mechanisms, in order to develop systems-based methods for tissue regeneration, develop drugs/biologics or other therapeutics and enhance the release of SRM into the body for natural healing through proper dietary, exercise and other lifestyle strategies. PMID:24649089

  7. Glial cell derived neurotrophic factor induces spermatogonial stem cell marker genes in chicken mesenchymal stem cells.

    PubMed

    Boozarpour, Sohrab; Matin, Maryam M; Momeni-Moghaddam, Madjid; Dehghani, Hesam; Mahdavi-Shahri, Naser; Sisakhtnezhad, Sajjad; Heirani-Tabasi, Asieh; Irfan-Maqsood, Muhammad; Bahrami, Ahmad Reza

    2016-06-01

    Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage differentiation. Advances in differentiation technology have also resulted in the conversion of MSCs to other kinds of stem cells. MSCs are considered as a suitable source of cells for biotechnology purposes because they are abundant, easily accessible and well characterized cells. Nowadays small molecules are introduced as novel and efficient factors to differentiate stem cells. In this work, we examined the potential of glial cell derived neurotrophic factor (GDNF) for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were isolated and characterized from chicken and cultured under treatment with all-trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression analysis of specific genes after 7days of RA treatment, as examined by RT-PCR, proved positive for some germ cell markers such as CVH, STRA8, PLZF and some genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as well as other genes which were induced after RA treatment. These data illustrated that GDNF is relatively more effective in diverting chicken MSCs towards Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent to obtain transgenic poultry, nevertheless, exploitability of these cells should be verified by more experiments.

  8. Stem cells of the skin epithelium

    PubMed Central

    Alonso, Laura; Fuchs, Elaine

    2003-01-01

    Tissue stem cells form the cellular base for organ homeostasis and repair. Stem cells have the unusual ability to renew themselves over the lifetime of the organ while producing daughter cells that differentiate into one or multiple lineages. Difficult to identify and characterize in any tissue, these cells are nonetheless hotly pursued because they hold the potential promise of therapeutic reprogramming to grow human tissue in vitro, for the treatment of human disease. The mammalian skin epithelium exhibits remarkable turnover, punctuated by periods of even more rapid production after injury due to burn or wounding. The stem cells responsible for supplying this tissue with cellular substrate are not yet easily distinguishable from neighboring cells. However, in recent years a significant body of work has begun to characterize the skin epithelial stem cells, both in tissue culture and in mouse and human skin. Some epithelial cells cultured from skin exhibit prodigious proliferative potential; in fact, for >20 years now, cultured human skin has been used as a source of new skin to engraft onto damaged areas of burn patients, representing one of the first therapeutic uses of stem cells. Cell fate choices, including both self-renewal and differentiation, are crucial biological features of stem cells that are still poorly understood. Skin epithelial stem cells represent a ripe target for research into the fundamental mechanisms underlying these important processes. PMID:12913119

  9. Transdifferentiation of Stem Cells: A Critical View

    NASA Astrophysics Data System (ADS)

    Gruh, Ina; Martin, Ulrich

    Recently a large amount of new data on the plasticity of stem cells of various lineages have emerged, providing new perspectives especially for the therapeutic application of adult stem cells. Previously unknown possibilities of cell differentiation beyond the known commitment of a given stem cell have been described using keywords such as "blood to liver," or "bone to brain." Controversies on the likelihood, as well as the biological significance, of these conversions almost immediately arose within this young field of stem cell biology. This chapter will concentrate on these controversies and focus on selected examples demonstrating the technical aspects of stem cell transdifferentiation and the evaluation of the tools used to analyze these events.

  10. Isolation and Culture of Embryonic Stem Cells, Mesenchymal Stem Cells, and Dendritic Cells from Humans and Mice.

    PubMed

    Kar, Srabani; Mitra, Shinjini; Banerjee, Ena Ray

    2016-01-01

    Stem cells are cells capable of proliferation, self-renewal, and differentiation into specific phenotypes. They are an essential part of tissue engineering, which is used in regenerative medicine in case of degenerative diseases. In this chapter, we describe the methods of isolating and culturing various types of stem cells, like human embryonic stem cells (hESCs), human umbilical cord derived mesenchymal stem cells (hUC-MSCs), murine bone marrow derived mesenchymal stem cells (mBM-MSCs), murine adipose tissue derived mesenchymal stem cells (mAD-MSCs), and murine bone marrow derived dendritic cells (mBMDCs). All these cell types can be used in tissue engineering techniques.

  11. Isolation and manipulation of mouse trophoblast stem cells.

    PubMed

    Hayakawa, Koji; Himeno, Emi; Tanaka, Satoshi; Kunath, Tilo

    2015-02-02

    The isolation of stable trophoblast stem (TS) cell lines from early mouse embryos has provided a useful cell culture model to study trophoblast development. TS cells are derived from pre-implantation blastocysts or from the extraembryonic ectoderm of early post-implantation embryos. The derivation and maintenance of mouse TS cells is dependent upon continuous fibroblast growth factor (FGF) signaling. Gene expression analysis, differentiation in culture, and chimera formation show that TS cells accurately model the mouse trophoblast lineage. This unit describes how to derive, maintain, and manipulate TS cells, including DNA transfection and chimera formation.

  12. Epigenetic targeting of ovarian cancer stem cells.

    PubMed

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer.

  13. Epigenetic Targeting of Ovarian Cancer Stem Cells

    PubMed Central

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P.; Matei, Daniela

    2014-01-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer (OC). As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cell (OCSC). In this study, we tested the hypothesis that DNA hypomethylating agents may be able to reset OCSC towards a differentiated phenotype, by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH+ OC cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low dose SGI-110 reduced the stem-like properties of ALDH+ cells, including their tumor initiating capacity, resensitized these OCSCs to platinum, and induced re-expression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by re-programming residual cancer stem-like cells. Further, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  14. Improving Stem Cell Therapeutics with Mechanobiology

    PubMed Central

    Shin, Jae-Won; Mooney, David J.

    2017-01-01

    In recent years, it has become clear that mechanical cues play an integral role in maintaining stem cell functions. Here we discuss how integrating physical approaches and engineering principles in stem cell biology, including culture systems, preclinical models, and functional assessment, may improve clinical application in regenerative medicine. PMID:26748752

  15. Stem Cell Research and Health Education

    ERIC Educational Resources Information Center

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2008-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the…

  16. Stem Cell Transplants in Cancer Treatment

    Cancer.gov

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  17. Stem cell banking: between traceability and identifiability.

    PubMed

    Knoppers, Bartha M; Isasi, Rosario

    2010-10-05

    Stem cell banks are increasingly seen as an essential resource of biological materials for both basic and translational research. Stem cell banks support transnational access to quality-controlled and ethically sourced stem cell lines from different origins and of varying grades. According to the Organisation for Economic Co-operation and Development, advances in regenerative medicine are leading to the development of a bioeconomy, 'a world where biotechnology contributes to a significant share of economic output'. Consequently, stem cell banks are destined to constitute a pillar of the bioeconomy in many countries. While certain ethical and legal concerns are specific to the nature of stem cells, stem cell banking could do well to examine the approaches fostered by tissue banking generally. Indeed, the past decade has seen a move to simplify and harmonize biological tissue and data banking so as to foster international interoperability. In particular, the issues of consent and of traceability illustrate not only commonalities but the opportunity for stem cell banking to appreciate the lessons learned in biobanking generally. This paper analyzes convergence and divergence in issues surrounding policy harmonization, transnational sharing, informed consent, traceability and return of results in the context of stem cell banks.

  18. Pathological modifications of plant stem cell destiny

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

  19. Organ or Stem Cell Transplant and Your Mouth

    MedlinePlus

    ... Stem Cell Transplant and Your Mouth Organ or Stem Cell Transplant and Your Mouth Main Content Key Points​ ... Your Dentist Before Transplant Before an organ or stem cell transplant, have a dental checkup. Your mouth should ...

  20. Epigenetics and chromatin plasticity in embryonic stem cells

    PubMed Central

    Přikrylová, Terézia; Pacherník, Jiří; Kozubek, Stanislav; Bártová, Eva

    2013-01-01

    The study of embryonic stem cells is in the spotlight in many laboratories that study the structure and function of chromatin and epigenetic processes. The key properties of embryonic stem cells are their capacity for self-renewal and their pluripotency. Pluripotent stem cells are able to differentiate into the cells of all three germ layers, and because of this property they represent a promising therapeutic tool in the treatment of diseases such as Parkinson’s disease and diabetes, or in the healing of lesions after heart attack. As the basic nuclear unit, chromatin is responsible for the regulation of the functional status of cells, including pluripotency and differentiation. Therefore, in this review we discuss the functional changes in chromatin during differentiation and the correlation between epigenetics events and the differentiation potential of embryonic stem cells. In particular we focus on post-translational histone modification, DNA methylation and the heterochromatin protein HP1 and its unique function in mouse and human embryonic stem cells. PMID:23951389

  1. Computational Tools for Stem Cell Biology.

    PubMed

    Bian, Qin; Cahan, Patrick

    2016-12-01

    For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the past several years, a new subdiscipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate.

  2. Cancer Stem Cells: Repair Gone Awry?

    PubMed Central

    Rangwala, Fatima; Omenetti, Alessia; Diehl, Anna Mae

    2011-01-01

    Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on this process, and thus may unmask defective regulation of pathways, such as Hedgehog (Hh), that modulate progenitor cell fate. Hh pathway dysregulation has been demonstrated in many types of cancer, including pancreatic and liver cancers, in which defective Hh signaling has been linked to outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements. Hence, the Hh pathway might be a therapeutic target in such tumors. PMID:21188169

  3. Clinical trials for stem cell transplantation: when are they needed?

    PubMed

    Van Pham, Phuc

    2016-04-27

    In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.

  4. [Application prospect of adult stem cells in male infertility].

    PubMed

    Yang, Rui-Feng; Xiong, Cheng-Liang

    2013-05-01

    The study on stem cells is a hot field in biomedical science in recent years, and has furthered from laboratory to clinical application. Stem cells, according to their developmental stage and differential properties, can be divided into embryonic stem cells, induced PS cells and adult stem cells, among which, adult stem cells have already been applied to the clinical treatment of many systemic diseases. Currently, the study of spermatogonial stem cells and adult stem cells is in the front of the basic researches on the treatment of male infertility, but the time has not yet arrived for their clinical application. This paper outlines the application prospect of adult stem cells in male infertility.

  5. [Stem cells--cloning, plasticity, bioethic].

    PubMed

    Pflegerl, Pamina; Keller, Thomas; Hantusch, Brigitte; Hoffmann, Thomas Sören; Kenner, Lukas

    2008-01-01

    Stem cells with certain characteristics have become promising tools for molecular medicine. They have the potential to self-regenerate and to differentiate into specific tissues. Besides their great potential, embryonic stem cells (ESC) run the risk of enhanced tumorigenesis. The use of human embryonic stem cells (hESC) is ethically problematic because their isolation involves the destruction of human embryos. Recently developed methods generate are able to pluripotent stem cells from fibroblasts. Alternatives for ESC are adult stem cells (ASC) derived from bone marrow, cord blood, amniotic fluid and other tissues. The following article is on the basis of testimony of Lukas Kenner for the German Bundestag about the use of ESC for research, therapy and drug development. Ethical aspects are taken into consideration.

  6. [Biological properties of spermatogonial stem cell niches].

    PubMed

    Li, Ling-Ling; Liu, Yang; Jin, Bo; Zhang, Xue-Ming

    2012-04-01

    The self-renewal and differentiation of adult stem cells are closely related to their niches. Naturally, spermatogonial stem cells (SSCs) are the only adult stem cells in the body, which can transfer genetic information into the offspring. An insight into the modulation of the self-renewal and differentiation of SSCs can help elucidate the mechanisms of spermatogenesis and investigate the proliferation and differentiation of other adult stem cells. Therefore, the SSC system provides an ideal model for researches on the adult stem cell niche. More and more evidence indicates that the self-renewal and differentiation of SSCs are regulated by their niches. Based on our previous work and other related findings recently reported, this article presents an overview on the biological properties of SSC niches and their relationship with the self-renewal and differentiation of SSCs, focusing on the basic properties and components of SSC niches and various regulatory factors they produce.

  7. Mesenchymal stem cells stimulate intestinal stem cells to repair radiation-induced intestinal injury

    PubMed Central

    Gong, Wei; Guo, Mengzheng; Han, Zhibo; Wang, Yan; Yang, Ping; Xu, Chang; Wang, Qin; Du, Liqing; Li, Qian; Zhao, Hui; Fan, Feiyue; Liu, Qiang

    2016-01-01

    The loss of stem cells residing in the base of the intestinal crypt has a key role in radiation-induced intestinal injury. In particular, Lgr5+ intestinal stem cells (ISCs) are indispensable for intestinal regeneration following exposure to radiation. Mesenchymal stem cells (MSCs) have previously been shown to improve intestinal epithelial repair in a mouse model of radiation injury, and, therefore, it was hypothesized that this protective effect is related to Lgr5+ ISCs. In this study, it was found that, following exposure to radiation, transplantation of MSCs improved the survival of the mice, ameliorated intestinal injury and increased the number of regenerating crypts. Furthermore, there was a significant increase in Lgr5+ ISCs and their daughter cells, including Ki67+ transient amplifying cells, Vil1+ enterocytes and lysozyme+ Paneth cells, in response to treatment with MSCs. Crypts isolated from mice treated with MSCs formed a higher number of and larger enteroids than those from the PBS group. MSC transplantation also reduced the number of apoptotic cells within the small intestine at 6 h post-radiation. Interestingly, Wnt3a and active β-catenin protein levels were increased in the small intestines of MSC-treated mice. In addition, intravenous delivery of recombinant mouse Wnt3a after radiation reduced damage in the small intestine and was radioprotective, although not to the same degree as MSC treatment. Our results show that MSCs support the growth of endogenous Lgr5+ ISCs, thus promoting repair of the small intestine following exposure to radiation. The molecular mechanism of action mediating this was found to be related to increased activation of the Wnt/β-catenin signaling pathway. PMID:27685631

  8. Peripheral blood stem cell mobilization failure.

    PubMed

    Kurnaz, Fatih; Kaynar, Leylagül

    2015-08-01

    Autologous hematopoietic stem cell transplantation (HSCT) is an important and often life saving treatment for many hematological malignancies and selected solid tumors. To rescue hematopoiesis after high-dose chemotherapy in autologous HSCT depends on maintaining sufficient stem cells. Hematopoietic stem cells and progenitor cells expressing CD34 in the BM are mobilized into the circulation with granulocyte-colony stimulating factor ± chemotherapy prior to autologous HSCT. One of the most important factors for success of autologous HSCT is hematopoietic stem cell (HSC) count. Minimum threshold for the engraftment of hematopoietic cells is accepted as 2 × 10(6) CD34 + cells/kg especially for platelet engraftment. Below this level it is defined as stem cell mobilization failure. There are several factors affecting stem cell mobilization: prior chemotherapy (such as fludarabine, melphalan, lenalidomide) and radiotherapy, age, type of disease, bone marrow cellularity. We tried to summarize the reasons of peripheral stem cell mobilization failure.

  9. Planarians, a tale of stem cells.

    PubMed

    Rossi, L; Salvetti, A; Batistoni, R; Deri, P; Gremigni, V

    2008-01-01

    Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues.

  10. Functional ion channels in stem cells

    PubMed Central

    Li, Gui-Rong; Deng, Xiu-Ling

    2011-01-01

    Bioelectrical signals generated by ion channels play crucial roles in excitation genesis and impulse conduction in excitable cells as well as in cell proliferation, migration and apoptosis in proliferative cells. Recent studies have demonstrated that multiple ion channels are heterogeneously present in different stem cells; however, patterns and phenotypes of ion channels are species- and/or origin-dependent. This editorial review focuses on the recent findings related to the expression of functional ion channels and the roles of these channels in regulation of cell proliferation in stem cells. Additional effort is required in the future to clarify the ion channel expression in different types of stem cells; special attention should be paid to the relationship between ion channels and stem cell proliferation, migration and differentiation. PMID:21607133

  11. Pluripotent Stem Cells and Gene Therapy

    PubMed Central

    Simara, Pavel; Motl, Jason A.; Kaufman, Dan S.

    2013-01-01

    Human pluripotent stem cells represent an accessible cell source for novel cell-based clinical research and therapies. With the realization of induced pluripotent stem cells (iPSCs), it is possible to produce almost any desired cell type from any patient's cells. Current developments in gene modification methods have opened the possibility for creating genetically corrected human iPSCs for certain genetic diseases that could be used later in autologous transplantation. Promising preclinical studies have demonstrated correction of disease-causing mutations in a number of hematological, neuronal and muscular disorders. This review aims to summarize these recent advances with a focus on iPSC generation techniques, as well as gene modification methods. We will then further discuss some of the main obstacles remaining to be overcome before successful application of human pluripotent stem cell-based therapy arrives in the clinic and what the future of stem cell research may look like. PMID:23353080

  12. An introduction to induced pluripotent stem cells.

    PubMed

    Hanley, Joanna; Rastegarlari, Ghasem; Nathwani, Amit C

    2010-10-01

    Recent landmark studies show that it is now possible to convert somatic cells, such as skin fibroblasts and B lymphocytes, into pluripotent stem cells that closely resemble embryonic stem cells. These induced pluripotent stem (iPS) cells can be generated without using human embryos or oocytes, thus bypassing some of the ethical issues that have limited the use of human embryonic stems (hES) cells. Additionally, they can be derived from the patient to be treated, thereby overcoming problems of immunological rejection associated with the use of allogeneic hES cell derived progenitors. Whilst these patient-specific iPS cells have great clinical potential, their immediate utility is likely to be in drug screening and for understanding the disease process. This review discusses the promise of iPS cells as well as the challenges to their use in the clinic.

  13. Translational research of adult stem cell therapy.

    PubMed

    Suzuki, Gen

    2015-11-26

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  14. High incidence of post-transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib-based regimens: a survey from the Rome transplant network.

    PubMed

    Marchesi, F; Mengarelli, A; Giannotti, F; Tendas, A; Anaclerico, B; Porrini, R; Picardi, A; Cerchiara, E; Dentamaro, T; Chierichini, A; Romeo, A; Cudillo, L; Montefusco, E; Tirindelli, M C; De Fabritiis, P; Annino, L; Petti, M C; Monarca, B; Arcese, W; Avvisati, G

    2014-02-01

    The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.

  15. Breast cancer stem cells and radiation

    NASA Astrophysics Data System (ADS)

    Phillips, Tiffany Marie

    2007-12-01

    The present studies explore the response of breast cancer stem cells (BCSC's) to radiation and the implications for clinical cancer treatment. Current cancer therapy eliminates bulky tumor mass but may fail to eradicate a critical tumor initiating cell population termed "cancer stem cells". These cells are potentially responsible for tumor formation, metastasis, and recurrence. Recently cancer stem cells have been prospectively identified in various malignancies, including breast cancer. The breast cancer stem cell has been identified by the surface markers CD44+/CD24 -(low). In vitro mammosphere cultures allow for the enrichment of the cancer stem cell population and were utilized in order to study differential characteristics of BCSC's. Initial studies found that BCSC's display increased radiation resistance as compared to other non-stem tumor cells. This resistance was accompanied by decreased H2AX phosphorylation, decreased reactive oxygen species formation, and increased phosphorylation of the checkpoint protein Chk1. These studies suggest differential DNA damage and repair within the BCSC population. Studies then examined the consequences of fractionated radiation on the BCSC population and found a two-fold increase in BCSC's following 5 x 3Gy. This observation begins to tie cancer stem cell self-renewal to the clinical stem cell phenomenon of accelerated repopulation. Accelerated repopulation is observed when treatment gaps increase between sequential fractions of radiotherapy and may be due to cancer stem cell symmetric self-renewal. The balance between asymmetric and symmetric stem cell division is vital for proper maintenance; deregulation is likely linked to cancer initiation and progression. The developmental Notch-1 pathway was found to regulate BCSC division. Over-expressing the constitutively active Notch-1-ICD in MCF7 cells produced an increase in the BCSC population. Additionally, radiation was observed to increase the expression of the Notch-1

  16. Stem cells and liver engineering.

    PubMed

    Ordovás, Laura; Park, Yonsil; Verfaillie, Catherine M

    2013-11-15

    Human hepatocytes, suitable for treatment of patients with liver failure, for the creation of bioartificial (BAL) devices, or for studies for toxicity and metabolization studies in the pharmaceutical industry, are in short supply due to the lack of donor organs. Therefore, methods that allow ex vivo expansion of hepatocytes with mature function are being pursued. One cell source, believed to be a possible inexhaustible source of hepatocytes, is pluripotent stem cells (PSCs). However, directed differentiation of PSCs to cells with features of adult hepatocytes is not yet possible. Differentiated progeny remains mixed and PSC progeny does not have a number of the functional features of mature hepatocytes. In this review article, we will address tools being developed that allow for the identification of mature hepatocytes, in a non-invasive manner; to perform lineage tracing of PSC progeny; and novel culture systems being created for the in vitro differentiation of PSCs to hepatocyte like cells, and for the maintenance of primary liver derived hepatocytes or PSC-derived hepatic progeny in culture. As conventional two-dimensional (2D) static culture conditions poorly recapitulate the in vivo cellular environment, we will discuss bioreactor systems for liver tissue engineering, both macro-scale and micro-scale culture systems.

  17. Stem cells from oral niches: a review

    PubMed Central

    Giordano, Guido; La Monaca, Gerardo; Annibali, Susanna; Cicconetti, Andrea; Ottolenghi, Livia

    2011-01-01

    Summary Aim Stem cell research in recent years have been considered the most advanced sort of medical-scientific research and early results have aroused great expectations. Also in dentistry many studies were performed with the final aim of obtaining new bone and new teeth. In this work we describe the state of the art in dental science stem cell research. Methods We have performed a web-based research on MEDLINE within (www.pubmed.gov). We have used “stem cells from human exfoliated deciduous teeth” (24 paper found), “periodontal ligament stem cells” (32 paper found), “stem cell apical papilla” (16 paper found), “dental pulp stem cells” (136 paper found) as keywords for research. For each keyword we have performed a complete review focusing on knowledge upgrade. Results For each topic was created a selection of papers in chronological order of publication date so to give a timetable of the development of the research for each niche. Conclusion Research about stem cell from oral niches began in 2000 and every year papers publicated were more than the precedent. This review analysed about 180 articles most of which in the last 5 years. Dentla pulp from adult as from deciduous teeth seems to be the most valuable font of stem cells due to the pluripotential type of cells. PMID:22238715

  18. [Stem cells of mammalian brain: biology of the stem cells in vivo and in vitro].

    PubMed

    Viktorov, I V

    2001-01-01

    Stem cells are totipotent cells of the blastocyst (embryonal stem cells) and multipotent germinative cells of ento-, ecto-, and mesoderm that give rise to all tissues during embryogenesis. The stem cells have high proliferation activity and an unlimited capacity for self-production by symmetrical mitosis. Asymmetrical mitosis of the stem cells generates daughter cells ("progenitor cells") with unlimited proliferation potential. During differentiation, the progenitor cells give rise to definitive somatic cells. The stem and progenitor cells are preserved in most tissues of adult organism and provide for the constant replacement of the cells after their physiological death and damage. At the end of last century, stem cells were found in the brain of the adult mouse and rat and later in the brain of other mammals including humans. The subependymal zone of the lateral ventricles is considered the site of stem cells localization; however, there are indications of stem cells origination from ependyma while the subependymal zone serves as a collector of the progenitor cells where these cells divide. The problem of the localization of stem cells in a mature brain has not yet been resolved and is actively discussed. The stem and progenitor cells, as well as neuro- and gliogenesis, are most explored in the hippocampus and olfactory bulb. The progenitor cells migrate to the olfactory bulb from the subependymal zone of the lateral ventricles via a rostral migratory stream formed by the astrocytes, and then they differentiate to neural and glial cells. In the hippocampus, the neurons are formed in the subgranular zone of dentate gyrus. The discovery of stem and progenitor cells in the mature brain and their subsequent investigation point to an ongoing neuro- and gliogenesis in all periventricular sections of the brain and spinal cord during the whole animal or human lifespan. These processes proved to be related to the functional condition of CNS, and the de novo formed neural

  19. Regenerative medicine for the kidney: renotropic factors, renal stem/progenitor cells, and stem cell therapy.

    PubMed

    Maeshima, Akito; Nakasatomi, Masao; Nojima, Yoshihisa

    2014-01-01

    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.

  20. Curbing stem cell tourism in South Africa.

    PubMed

    Meissner-Roloff, Madelein; Pepper, Michael S

    2013-12-01

    Stem cells have received much attention globally due in part to the immense therapeutic potential they harbor. Unfortunately, malpractice and exploitation (financial and emotional) of vulnerable patients have also drawn attention to this field as a result of the detrimental consequences experienced by some individuals that have undergone unproven stem cell therapies. South Africa has had limited exposure to stem cells and their applications and, while any exploitation is detrimental to the field of stem cells, South Africa is particularly vulnerable in this regard. The current absence of adequate legislation and the inability to enforce existing legislation, coupled to the sea of misinformation available on the Internet could lead to an increase in illegitimate stem cell practices in South Africa. Circumstances are already precarious because of a lack of understanding of concepts involved in stem cell applications. What is more, credible and easily accessible information is not available to the public. This in turn cultivates fears born out of existing superstitions, cultural beliefs, rituals and practices. Certain cultural or religious concerns could potentially hinder the effective application of stem cell therapies in South Africa and novel ways of addressing these concerns are necessary. Understanding how scientific progress and its implementation will affect each individual and, consequently, the community, will be of cardinal importance to the success of the fields of stem cell therapy and regenerative medicine in South Africa. A failure to understand the ethical, cultural or moral ramifications when new scientific concepts are introduced could hinder the efficacy and speed of bringing discoveries to the patient. Neglecting proper procedure for establishing the field would lead to long delays in gaining public support in South Africa. Understanding the dangers of stem cell tourism - where vulnerable patients are subjected to unproven stem cell therapies that

  1. Stem cells for the treatment of diabetes.

    PubMed

    Noguchi, Hirofumi

    2007-02-01

    Diabetes mellitus is a devastating disease and over 6% of the population is affected worldwide. The success achieved over the last few years with islet transplantation suggest that diabetes can be cured by the replenishment of deficient beta cells. These observations are proof of concept and have intensified interest in treating diabetes or other diseases not only by cell transplantation but also by stem cells. Work with ES cells has not yet produced cells with the phenotype of true beta cells, but there has been recent progress in directing ES cells to the endoderm. Bone marrow-derived stem cells could initiate pancreatic regeneration. Pancreatic stem/progenitor cells have been identified, and the formation of new beta cells from duct, acinar and liver cells is an active area of investigation. Some agents including glucagon-like peptide-1/exendin-4 can stimulate the regeneration of beta cells in vivo. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. New technology, known as protein transduction technology, facilitates the differentiation of stem cells into insulin-producing cells. Recent progress in the search for new sources of beta cells has opened up several possibilities for the development of new treatments for diabetes.

  2. [Proteins support stem cells - use of protein therapeutics in hematopoietic stem cell transplantation].

    PubMed

    Meyer, Sara Christina; Stern, Martin

    2011-11-01

    Hematopoietic stem cell transplantation (HSCT) has evolved from a largely experimental therapeutic approach three decades ago to a well-established therapy today for many malignant and non-malignant disorders of the hematopoietic and the immune system. Although it is per se a therapy by transmission of cells, protein therapeutics such as growth factors and antibodies are relevant in all phases of a HSCT and substantially contribute to the success of this often only curative treatment. This review discusses HSCT with a particular focus on the protein therapeutics involved. Granulocyte colony stimulating factor (G-CSF) for mobilization of stem cells to the peripheral blood, the polyclonal anti-T-cell globulin (ATG) and the monoclonal antibodies alemtuzumab and etanercept for prophylaxis and therapy of graft versus host disease (GvHD) are highlighted. Also rituximab, palivizumab and polyclonal intravenous immunoglobulins for treating infections in post-transplant patients are discussed. Since our understanding of cell surface receptors, cytokine and signaling pathways is increasing, there will emerge new targets for directed therapy by proteins in the future. They may have the potential to further improve the success and to widen theapplication of HSCT.

  3. From adult stem cells to cancer stem cells: Oct-4 Gene, cell-cell communication, and hormones during tumor promotion.

    PubMed

    Trosko, James E

    2006-11-01

    Carcinogenesis is characterized by "initiation," "promotion," and "progression" phases. The "stem cell theory" and "de-differentiation" theories are used to explain the origin of cancer. Growth control for stem cells, which lack functional gap junctional intercellular communication (GJIC), involves negative soluble or niche factors, while for progenitor cells, it involves GJIC. Tumor promoters, hormones, and growth factors inhibit GJIC reversibly. Oncogenes stably inhibit GJIC. Cancer cells, which lack growth control and the ability to terminally differentiate and to apoptose, lack GJIC. The Oct3/4 gene, a POU (Pit-Oct-Unc) family of transcription factors was thought to be expressed only in embryonic stem cells and in tumor cells. With the availability of normal adult human stem cells, tests for the expression of Oct3/4 gene and the stem cell theory in human carcinogenesis became possible. Human breast, liver, pancreas, kidney, mesenchyme, and gastric stem cells, HeLa and MCF-7 cells, and canine tumors were tested with antibodies and polymerase chain reaction (PCR) primers for Oct3/4. Adult human breast stem cells, immortalized nontumorigenic and tumor cell lines, but not the normal differentiated cells, expressed Oct3/4. Adult human differentiated cells lose their Oct-4 expression. Oct3/4 is expressed in a few cells found in the basal layer of human skin epidermis. The data demonstrate that normal adult stem cells and cancer stem cells maintain expression of Oct3/4, consistent with the stem cell hypothesis of carcinogenesis. These Oct-4 positive cells might represent the "cancer stem cells." A strategy to target "cancer stem cells" is to suppress the Oct-4 gene in order to cause the cells to differentiate.

  4. Stem cells and regeneration in planarians.

    PubMed

    Handberg-Thorsager, Mette; Fernandez, Enrique; Salo, Emili

    2008-05-01

    Understanding stem cells is a major goal of current research because of its potential medical applications. Although great advances have been made, such as the culturing and differentiation of embryonic stem cells and reprogramming of cell fates, many basic questions remain unanswered. Describing the mechanisms underlying regeneration will help to understand the biology of stem cells and therefore to control their behavior. While regeneration is being studied in a variety of models, the planarian is particularly noteworthy. In this model system a fragment as small as 1/279 of the animal can regenerate completely within a few weeks. These animals can also grow and degrow--specifically degenerating certain tissues--according to environmental conditions, thus demonstrating a complete control of their stem cell dynamics. However, one of the most interesting aspects of the planarian model system is the presence of a unique type of stem cell that can differentiate into all cell types found in the organism, including the germ line. This represents a simple, extremely powerful, and accessible stem cell system in which to address a variety of important questions. In the last ten years, molecular, cellular, and bioinformatics tools have been established for use in this model, making it ideally placed for in vivo analysis of stem cells in their natural environment without ethical complications.

  5. [Stem cells: limitations and opportunities in Peru].

    PubMed

    Amiel-Pérez, José; Casado, Fanny

    2015-10-01

    Stem cells are defined as rare cells that are characterized by asymmetric division, a process known as self-renewal, and the potential to differentiate into more than one type of terminally differentiated cell. There is a diversity of stem cells including embryonic stem cells, which exist only during the first stages of human development, and many adult stem cells depending on the specific tissues from where they derive or the ones derived from mesenchymal or stromal tissues. On the other hand, there are induced pluripotent stem cells generated by genetic engineering with similar properties to embryonic stem cells that are derived from adult tissues without the ethical and legal limitations. In all cases, there are many questions that are being addressed by research in basic sciences to better inform clinical practice. In Peru, there is much to do refining techniques and improving methodologies, which requires experience, proper facilities and highly specialized human resources. However, there are interesting efforts to place Peruvian stem cell research in the international scientific arena.

  6. PLURIPOTENT STEM CELL APPLICATIONS FOR REGENERATIVE MEDICINE

    PubMed Central

    Angelos, Mathew G.; Kaufman, Dan S.

    2015-01-01

    Purpose of Review In this review, we summarize the current status of clinical trials using therapeutic cells produced from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We also discuss combined cell and gene therapy via correction of defined mutations in human pluripotent stem cells and provide commentary on key obstacles facing wide-scale clinical adoption of pluripotent stem cell-based therapy. Recent Findings Initial data suggest hESC/hiPSC-derived cell products used for retinal repair and spinal cord injury are safe for human use. Early stage studies for treatment of cardiac injury and diabetes are also in progress. However, there remain key concerns regarding the safety and efficacy of these cells that need to be addressed in additional well-designed clinical trials. Advances using the CRISPR/Cas9 gene-editing system offer an improved tool for more rapid and on-target gene correction of genetic diseases. Combined gene and cell therapy using human pluripotent stem cells may provide an additional curative approach for disabling or lethal genetic and degenerative diseases where there are currently limited therapeutic opportunities. Summary Human pluripotent stem cells are emerging as a promising tool to produce cells and tissues suitable for regenerative therapy for a variety of genetic and degenerative diseases. PMID:26536430

  7. Stem cells in pediatric heart failure.

    PubMed

    Pillekamp, F; Khalil, M; Emmel, M; Brockmeier, K; Hescheler, J

    2008-06-01

    Pediatric heart failure could be a target for regenerative therapy. Stem cell-based therapy has the potential to provide functional cardiomyocytes. Whereas adult stem cells have shown no or only minimal therapeutic benefit in adults with no evidence of transdifferentiation, embryonic stem cells can differentiate to any cell type, including cardiomyocytes. However, ethical concerns and immunological problems are associated with embryonic stem cells derived from the inner cell mass of blastocysts. Recently, somatic cells could be reprogrammed to a pluripotent state (i.e. induced pluripotent stem cells) with the help of transcription factors. This technique removes ethical and probably also immunological concerns. Nevertheless extensive experimental research will be necessary before cell replacement strategies become clinically applicable. Because the underlying pathophysiology differs significantly with age, caution is warranted extrapolating data obtained in experimental models of cardiac ischemia and clinical studies in adults to the pediatric population. Pediatric heart failure has a good prognosis if causal therapy is possible. However, some forms of congenital heart disease and especially dilated cardiomyopathy still have limited therapeutic options. Almost half of children with symptomatic cardiomyopathy receive a transplant or die within two years. The authors will review the relevant stem cell sources for cell-based treatments. And, given the differences of the underlying diseases between adult and pediatric patients with heart failure, it is contemplated which condition of pediatric patients with heart failure is most likely to benefit and which cell type would be appropriate.

  8. Signal propagation in stem-cell niches

    NASA Astrophysics Data System (ADS)

    Zhdanov, Vladimir P.

    2009-09-01

    Stem cells, maintaining tissue homeostasis, are nurtured in microscopic niches formed of so-called environmental cells. The kinetics of proliferation and differentiation of stem cells in such niches depend on their interaction with the messenger proteins secreted by environmental cells. We propose a generic mean-field kinetic model of the propagation of such signals. To motivate our study, we briefly describe a stem-cell niche in the Drosophila ovary. Our model is however applicable to other niches as well. In particular, it helps one to understand the necessary conditions for the niche function. For example, the model predicts that in the case of the Drosophila ovary each germline stem cell should have in the external membrane at least 700 receptors interacting with the signaling Dpp and Gpp proteins emanating from the cap cells.

  9. Multipotent Stem Cells in Cardiac Regeneration

    PubMed Central

    Karra, Ravi; Wu, Sean M.

    2008-01-01

    Summary The potential for stem cells to ameliorate or cure heart diseases has galvanized a cadre of cardiovascular translational and clinical scientists to take a “first-in-man” approach using autologous stem cells from a variety of tissues. However, recent clinical trial data show that when these cells are given by intracoronary infusion or direct myocardial injection, limited improvement in heart function occurs with no evidence of cardiomyogenesis. These studies illustrate the great need to understand the logic of cell-lineage commitment and the principles of cardiac differentiation. Recent identification of stem/progenitor cells of embryological origin with intrinsic competence to differentiate into multiple lineages within the heart offers new possibilities for cardiac regeneration. When combined with developments in nuclear reprogramming and provided that tumor risks and other challenges of embryonic cell transplantation can be overcome, the prospect of achieving autologous, cardiomyogenic, stem cell-based therapy may be within reach. PMID:18307403

  10. Odontogenic epithelial stem cells: hidden sources.

    PubMed

    Padma Priya, Sivan; Higuchi, Akon; Abu Fanas, Salem; Pooi Ling, Mok; Kumari Neela, Vasantha; Sunil, P M; Saraswathi, T R; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh

    2015-12-01

    The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed.

  11. Presence of stem/progenitor cells in the rat penis.

    PubMed

    Lin, Guiting; Alwaal, Amjad; Zhang, Xiaoyu; Wang, Jianwen; Wang, Lin; Li, Huixi; Wang, Guifang; Ning, Hongxiu; Lin, Ching-Shwun; Xin, Zhongcheng; Lue, Tom F

    2015-01-15

    Tissue resident stem cells are believed to exist in every organ, and their identification is commonly done using a combination of immunostaining for putative stem cell markers and label-retaining cell (LRC) strategy. In this study, we employed these approaches to identify potential stem cells in the penis. Newborn rats were intraperitoneally injected with thymidine analog, 5-ethynyl-2-deoxyuridine (EdU), and their penis was harvested at 7 h, 3 days, 1 week, and 4 weeks. It was processed for EdU stains and immunofluorescence staining for stem cell markers A2B5, PCNA, and c-kit. EdU-positive cells were counted for each time point and co-localized with each stem cell marker, then isolated and cultured in vitro followed by their characterization using flowcytometry and immunofluorescence. At 7 h post-EdU injection, 410 ± 105.3 penile corporal cells were labeled in each cross-section (∼28%). The number of EdU-positive cells at 3 days increased to 536 ± 115.6, while their percentage dropped to 25%. Progressively fewer EdU-positive cells were present in the sacrificed rat penis at longer time points (1 and 4 weeks). They were mainly distributed in the subtunic and perisinusoidal spaces, and defined as subtunic penile progenitor cells (STPCs) and perisinusoidal penile progenitor cells (PPCs). These cells expressed c-kit, A2B5, and PCNA. After culturing in vitro, only ∼0.324% corporal cells were EdU-labeled LRCs and expressed A2B5/PCNA. Therefore, labeling of penis cells by EdU occurred randomly, and label retaining was not associated with expression of c-kit, A2B5, or PCNA. The penile LRCs are mainly distributed within the subtunic and perisinusoidal space.

  12. [Hematopoietic stem cell transplantation in autoimmune diseases].

    PubMed

    Albarracín, Flavio; López Meiller, María José; Naswetter, Gustavo; Longoni, Héctor

    2008-01-01

    Transplantation of hematopoietic stem cells, which are capable of self renewal and reconstitution of all types of blood cells, can be a treatment for numerous potential lethal diseases, including leukemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant multiple sclerosis, lupus and systemic sclerosis. Studies in animal models show that the transfer of hematopoietic stem cells can reverse autoimmunity. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.

  13. Update on small intestinal stem cells.

    PubMed

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-08-07

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

  14. Stem cell applications in military medicine

    PubMed Central

    2011-01-01

    There are many similarities between health issues affecting military and civilian patient populations, with the exception of the relatively small but vital segment of active soldiers who experience high-energy blast injuries during combat. A rising incidence of major injuries from explosive devices in recent campaigns has further complicated treatment and recovery, highlighting the need for tissue regenerative options and intensifying interest in the possible role of stem cells for military medicine. In this review we outline the array of tissue-specific injuries typically seen in modern combat - as well as address a few complications unique to soldiers - and discuss the state of current stem cell research in addressing each area. Embryonic, induced-pluripotent and adult stem cell sources are defined, along with advantages and disadvantages unique to each cell type. More detailed stem cell sources are described in the context of each tissue of interest, including neural, cardiopulmonary, musculoskeletal and sensory tissues, with brief discussion of their potential role in regenerative medicine moving forward. Additional commentary is given to military stem cell applications aside from regenerative medicine, such as blood pharming, immunomodulation and drug screening, with an overview of stem cell banking and the unique opportunity provided by the military and civilian overlap of stem cell research. PMID:22011454

  15. Stem cell tracking using iron oxide nanoparticles.

    PubMed

    Bull, Elizabeth; Madani, Seyed Yazdan; Sheth, Roosey; Seifalian, Amelia; Green, Mark; Seifalian, Alexander M

    2014-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.

  16. Stem cell applications in military medicine.

    PubMed

    Christopherson, Gregory T; Nesti, Leon J

    2011-10-19

    There are many similarities between health issues affecting military and civilian patient populations, with the exception of the relatively small but vital segment of active soldiers who experience high-energy blast injuries during combat. A rising incidence of major injuries from explosive devices in recent campaigns has further complicated treatment and recovery, highlighting the need for tissue regenerative options and intensifying interest in the possible role of stem cells for military medicine. In this review we outline the array of tissue-specific injuries typically seen in modern combat - as well as address a few complications unique to soldiers--and discuss the state of current stem cell research in addressing each area. Embryonic, induced-pluripotent and adult stem cell sources are defined, along with advantages and disadvantages unique to each cell type. More detailed stem cell sources are described in the context of each tissue of interest, including neural, cardiopulmonary, musculoskeletal and sensory tissues, with brief discussion of their potential role in regenerative medicine moving forward. Additional commentary is given to military stem cell applications aside from regenerative medicine, such as blood pharming, immunomodulation and drug screening, with an overview of stem cell banking and the unique opportunity provided by the military and civilian overlap of stem cell research.

  17. Time to reconsider stem cell induction strategies.

    PubMed

    Denker, Hans-Werner

    2012-12-17

    Recent developments in stem cell research suggest that it may be time to reconsider the current focus of stem cell induction strategies. During the previous five years, approximately, the induction of pluripotency in somatic cells, i.e., the generation of so-called 'induced pluripotent stem cells' (iPSCs), has become the focus of ongoing research in many stem cell laboratories, because this technology promises to overcome limitations (both technical and ethical) seen in the production and use of embryonic stem cells (ESCs). A rapidly increasing number of publications suggest, however, that it is now possible to choose instead other, alternative ways of generating stem and progenitor cells bypassing pluripotency. These new strategies may offer important advantages with respect to ethics, as well as to safety considerations. The present communication discusses why these strategies may provide possibilities for an escape from the dilemma presented by pluripotent stem cells (self-organization potential, cloning by tetraploid complementation, patenting problems and tumor formation risk).

  18. Current understanding concerning intestinal stem cells

    PubMed Central

    Cui, Shuang; Chang, Peng-Yu

    2016-01-01

    In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same. PMID:27610020

  19. Islet transplantation versus stem cells for the cell therapy of type 1 diabetes mellitus.

    PubMed

    Basta, G; Montanucci, P; Calafiore, R

    2015-12-01

    Pancreatic islet cell transplantation has represented the mainstay of cell therapy for the potential, final cure of type 1 diabetes mellitus (T1D), along the past two decades. Unfortunately, the restricted availability of cadaveric human donor pancreases coupled with heavy side effects of the recipient's general immunosuppression, have severely crippled progress of this approach into clinical trials. Only a few excellence centers, worldwide, have thus far accrued still quite marginal clinical success. In an attempt to overcome the limits of islet transplantation new technologies for use of several stem cell lineages are being under investigation, with initial experimental evidence of success. Essentially, the actual lines of research involve attempts to either activate native endogenous stem cells that replace diseased/dead cells, by a cell regeneration process, or condition other stem cells to acquire the functional properties of the targeted cells to be substituted (i.e., beta-cell-like elements associated with insulin secretory competence). A wide array of stem cells may fulfill this task, from embryonic (whose use still faces strong ethical barriers), to adult, to induced pluripotent stem cells. Mesenchymal adult stem cells, retrievable from many different sites, including adipose tissue, bone marrow and post-partum umbilical cord Wharton Jelly, seem to couple plastic to immunoregulatory properties that might greatly help progress for the disease cure.

  20. Current stem cell based therapies in diabetes

    PubMed Central

    Lilly, Meredith A; Davis, Meghan F; Fabie, Josh E; Terhune, Elizabeth B; Gallicano, G Ian

    2016-01-01

    Diabetes is a disease with wide-ranging personal and societal impacts that has been managed medicinally for over half a century. Since the discovery of stem cells, pancreatic islet regeneration has become a central target for clinical application that has the potential to decrease or eliminate the need for insulin administration and adjunctive medications. The discovery of alternative routes to pluripotency that bypass the ethical implications of embryonic stem cells has significantly expanded the horizons of stem cell based therapy. Engraftment of mature insulin producing cells derived from induced pluripotent stem cells may represent the most promising treatment strategy for diabetic patients with impaired β-cell function. These cells are easily accessible and have been shown to closely mimic endogenous β-cell function in vivo. While the risks of oncogenesis and transplant rejection are still of great concern, large strides have been made on both fronts with the application of integration free induction strategies and the ongoing development of microcapsules that cloak implanted cells from an autoimmune response. This review will focus on the progress and remaining obstacles in diabetes related stem cell research, and will specifically discuss approaches using embryonic, induced pluripotent, germline and mesenchymal derived stem cells. PMID:27853630

  1. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed.

  2. Cardiac stem cell therapy: Have we put too much hype in which cell type to use?

    PubMed

    Ye, Jianqin; Yeghiazarians, Yerem

    2015-09-01

    Injection of various stem cells has been tested with the hopes of improving cardiac function after a myocardial infarction (MI). However, there is continued controversy as to which cell type is best for repair. Due to technical differences in cell isolation, processing, delivery, and cardiac functional assessment by various investigators, it has been difficult to directly compare the results of different cells. Using same techniques to evaluate the efficacy of different cell types, we have separately delivered bone marrow cells (BMCs), cardiospheres (CSs), CS-derived Sca-1(+)/CD45(-) cells, human embryonic stem cell-derived cardiomyocytes, and BMC extract into infarcted murine myocardium and found that all of these treatments reduce infarct size and improve cardiac function post-MI similarly without one regimen being superior to another. The beneficial effects appear to be via paracrine influences. Different progenitors lead to improved cardiac function post-MI, but it is premature to hype any specific cell type at this time.

  3. Cellular quiescence in mammary stem cells and breast tumor stem cells: got testable hypotheses?

    PubMed

    Harmes, David C; DiRenzo, James

    2009-03-01

    Cellular quiescence is a state of reversible cell cycle arrest and has more recently been shown to be a blockade to differentiation and to correlate with resistance to cancer chemotherapeutics and other xenobiotics; features that are common to adult stem cells and possibly tumor stem cells. The biphasic kinetics of mammary regeneration, coupled to its cyclic endocrine control suggest that mammary stem cells most likely divide during a narrow window of the regenerative cycle and return to a state of quiescence. This would enable them to retain their proliferative capacity, resist differentiation signals and preserve their prolonged life span. There is accumulating evidence that mammary stem cells and other adult stem cells utilize quiescence for this purpose, however the degree to which tumor stem cells do so is largely unknown. The retained proliferative capacity of mammary stem cells likely enables them to accumulate and harbor mutations that lead to breast cancer initiation. However it is currently unclear if these causative lesions lead to defective or deranged quiescence in mammary stem cells. Evidence of such effects could potentially lead to the development of diagnostic systems that monitor mammary stem cell quiescence or activation. Such systems may be useful for the evaluation of patients who are at significant risk of breast cancer. Additionally quiescence has been postulated to contribute to therapeutic resistance and tumor recurrence. This review aims to evaluate what is known about the mechanisms governing cellular quiescence and the role of tumor stem cell quiescence in breast cancer recurrence.

  4. Engineering nanoscale stem cell niche: direct stem cell behavior at cell-matrix interface.

    PubMed

    Zhang, Yan; Gordon, Andrew; Qian, Weiyi; Chen, Weiqiang

    2015-09-16

    Biophysical cues on the extracellular matrix (ECM) have proven to be significant regulators of stem cell behavior and evolution. Understanding the interplay of these cells and their extracellular microenvironment is critical to future tissue engineering and regenerative medicine, both of which require a means of controlled differentiation. Research suggests that nanotopography, which mimics the local, nanoscale, topographic cues within the stem cell niche, could be a way to achieve large-scale proliferation and control of stem cells in vitro. This Progress Report reviews the history and contemporary advancements of this technology, and pays special attention to nanotopographic fabrication methods and the effect of different nanoscale patterns on stem cell response. Finally, it outlines potential intracellular mechanisms behind this response.

  5. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    PubMed

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  6. Induced pluripotent stem (iPS) cells from human fetal stem cells.

    PubMed

    Guillot, Pascale V

    2016-02-01

    Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications.

  7. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    DTIC Science & Technology

    2015-07-01

    AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM ELEMENT NUMBER 6...some oncogene function in determining molecular phenotypes. To test this hypothesis, we proposed to transform neural stem cells (NSCs) and neural

  8. Minireview: Nuclear Receptors, Hematopoiesis, and Stem Cells

    PubMed Central

    Chute, John P.; Ross, Joel R.; McDonnell, Donald P.

    2010-01-01

    Nuclear receptors (NRs) regulate a panoply of biological processes, including the function and development of cells within the hematopoietic and immune system, such as erythrocytes, monocytes, and lymphocytes. Significantly less is known regarding the function of NRs in regulating the fate of hematopoietic stem cells (HSCs), the self-renewing, pluripotent cells that give rise to the entirety of the blood and immune systems throughout the lifetime of an individual. Several recent studies suggest, either directly or indirectly, a role for members of the NR family in regulating the differentiation and self-renewal of HSCs, embryonic stem cells, and induced pluripotent stem cells. Herein, we review in detail the function of specific NRs in controlling HSC and other stem cell fate and propose a framework through which these observations can be translated into therapeutic amplification of HSCs for clinical purposes. PMID:19934345

  9. Analytical strategies for studying stem cell metabolism

    PubMed Central

    Arnold, James M.; Choi, William T.; Sreekumar, Arun

    2015-01-01

    Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology. PMID:26213533

  10. Analytical strategies for studying stem cell metabolism.

    PubMed

    Arnold, James M; Choi, William T; Sreekumar, Arun; Maletić-Savatić, Mirjana

    2015-04-01

    Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology.

  11. Time to Reconsider Stem Cell Induction Strategies

    PubMed Central

    Denker, Hans-Werner

    2012-01-01

    Recent developments in stem cell research suggest that it may be time to reconsider the current focus of stem cell induction strategies. During the previous five years, approximately, the induction of pluripotency in somatic cells, i.e., the generation of so-called ‘induced pluripotent stem cells’ (iPSCs), has become the focus of ongoing research in many stem cell laboratories, because this technology promises to overcome limitations (both technical and ethical) seen in the production and use of embryonic stem cells (ESCs). A rapidly increasing number of publications suggest, however, that it is now possible to choose instead other, alternative ways of generating stem and progenitor cells bypassing pluripotency. These new strategies may offer important advantages with respect to ethics, as well as to safety considerations. The present communication discusses why these strategies may provide possibilities for an escape from the dilemma presented by pluripotent stem cells (self-organization potential, cloning by tetraploid complementation, patenting problems and tumor formation risk). PMID:24710555

  12. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    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. PMID:24757526

  13. Determination of telomerase activity in stem cells and non-stem cells of breast cancer.

    PubMed

    Li, Zhi; He, Yanli; Zhang, Jiahua; Zhang, Jinghui; Huang, Tao

    2007-07-01

    Although all normal tissue cells, including stem cells, are genetically homologous, variation in gene expression patterns has already determined the distinct roles for individual cells in the physiological process due to the occurrence of epigenetic modification. This is of special importance for the existence of tissue stem cells because they are exclusively immortal within the body, capable of self-replicating and differentiating by which tissues renew and repair itself and the total tissue cell population maintains a steady-state. Impairment of tissue stem cells is usually accompanied by a reduction in cell number, slows down the repair process and causes hypofunction. For instance, chemotherapy usually leads to depression of bone marrow and hair loss. Cellular aging is closely associated with the continuous erosion of the telomere while activation of telomerase repairs and maintains telomeres, thus slowing the aging process and prolonging cell life. In normal adults, telomerase activation mainly presents in tissue stem cells and progenitor cells giving them unlimited growth potential. Despite the extensive demonstration of telomerase activation in malignancy (> 80%), scientists found that heterogeneity also exists among the tumor cells and only minorities of cells, designated as cancer stem cells, undergo processes analogous to the self-renewal and differentiation of normal stem cells while the rest have limited lifespans. In this study, telomerase activity was measured and compared in breast cancer stem cells and non-stem cells that were phenotypically sorted by examining surface marker expression. The results indicated that cancer stem cells show a higher level of enzyme activity than non-stem cells. In addition, associated with the repair of cancer tissue (or relapse) after chemotherapy, telomerase activity in stem cells was markedly increased.

  14. Interspecies Chimerism with Mammalian Pluripotent Stem Cells.

    PubMed

    Wu, Jun; Platero-Luengo, Aida; Sakurai, Masahiro; Sugawara, Atsushi; Gil, Maria Antonia; Yamauchi, Takayoshi; Suzuki, Keiichiro; Bogliotti, Yanina Soledad; Cuello, Cristina; Morales Valencia, Mariana; Okumura, Daiji; Luo, Jingping; Vilariño, Marcela; Parrilla, Inmaculada; Soto, Delia Alba; Martinez, Cristina A; Hishida, Tomoaki; Sánchez-Bautista, Sonia; Martinez-Martinez, M Llanos; Wang, Huili; Nohalez, Alicia; Aizawa, Emi; Martinez-Redondo, Paloma; Ocampo, Alejandro; Reddy, Pradeep; Roca, Jordi; Maga, Elizabeth A; Esteban, Concepcion Rodriguez; Berggren, W Travis; Nuñez Delicado, Estrella; Lajara, Jeronimo; Guillen, Isabel; Guillen, Pedro; Campistol, Josep M; Martinez, Emilio A; Ross, Pablo Juan; Izpisua Belmonte, Juan Carlos

    2017-01-26

    Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.

  15. Cancer stem cells, cancer cell plasticity and radiation therapy.

    PubMed

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.

  16. Stem cells engineering for cell-based therapy.

    PubMed

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  17. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    NASA Astrophysics Data System (ADS)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  18. Cancer stem cells and differentiation therapy.

    PubMed

    Sell, Stewart

    2006-01-01

    Cancers arise from stem cells in adult tissues and the cells that make up a cancer reflect the same stem cell --> progeny --> differentiation progression observed in normal tissues. All adult tissues are made up of lineages of cells consisting of tissue stem cells and their progeny (transit-amplifying cells and terminally differentiated cells); the number of new cells produced in normal tissue lineages roughly equals the number of old cells that die. Cancers result from maturation arrest of this process, resulting in continued proliferation of cells and a failure to differentiate and die. The biological behavior, morphological appearance, and clinical course of a cancer depend on the stage of maturation at which the genetic lesion is activated. This review makes a comparison of cancer cells to embryonic stem cells and to adult tis sue stem cells while addressing two basic questions: (1) Where do cancers come from?, and (2) How do cancers grow? The answers to these questions are critical to the development of approaches to the detection, prevention, and treatment of cancer.

  19. Evidence for Human Lung Stem Cells

    PubMed Central

    Kajstura, Jan; Rota, Marcello; Hall, Sean R.; Hosoda, Toru; D’Amario, Domenico; Sanada, Fumihiro; Zheng, Hanqiao; Ogórek, Barbara; Rondon-Clavo, Carlos; Ferreira-Martins, João; Matsuda, Alex; Arranto, Christian; Goichberg, Polina; Giordano, Giovanna; Haley, Kathleen J.; Bardelli, Silvana; Rayatzadeh, Hussein; Liu, Xiaoli; Quaini, Federico; Liao, Ronglih; Leri, Annarosa; Perrella, Mark A.; Loscalzo, Joseph; Anversa, Piero

    2011-01-01

    BACKGROUND Although progenitor cells have been described in distinct anatomical regions of the lung, description of resident stem cells has remained elusive. METHODS Surgical lung-tissue specimens were studied in situ to identify and characterize human lung stem cells. We defined their phenotype and functional properties in vitro and in vivo. RESULTS Human lungs contain undifferentiated human lung stem cells nested in niches in the distal airways. These cells are self-renewing, clonogenic, and multipotent in vitro. After injection into damaged mouse lung in vivo, human lung stem cells form human bronchioles, alveoli, and pulmonary vessels integrated structurally and functionally with the damaged organ. The formation of a chimeric lung was confirmed by detection of human transcripts for epithelial and vascular genes. In addition, the self-renewal and long-term proliferation of human lung stem cells was shown in serial-transplantation assays. CONCLUSIONS Human lungs contain identifiable stem cells. In animal models, these cells participate in tissue homeostasis and regeneration. They have the undemonstrated potential to promote tissue restoration in patients with lung disease. (Funded by the National Institutes of Health.) PMID:21561345

  20. Growing vascularized heart tissue from stem cells.

    PubMed

    Lim, Shiang Y; Hernández, Damián; Dusting, Gregory J

    2013-08-01

    The promise of stem cells to repair the heart after damage or heart attack has not been realized because most such cells are lost after transplantation. A new approach is to grow substantial viable pieces of cardiac tissue from human stem cells by cardiac tissue engineering. Such constructs must be fully vascularized and perfused to ensure the viability of clinically relevant volumes of tissue. This requires careful choice of cells, culture conditions, a biomaterial to act as scaffold, and crucial strategies for vascularization. Autologous stem cells with high plasticity, which would avoid the need for antirejection therapies after transplantation, are an attractive source of both cardiomyocytes and vascular cells. Most stem cells also have inherent paracrine activity, releasing cytoprotective factors and growth-promoting cytokines that can further stimulate tissue regeneration and neovascularization through recruitment of endogenous stem and progenitor cells. Current advances for growing vascularized and functional cardiac constructs with human stem cells are described, bringing us a step closer to the engineering of complex cardiac tissues such as pacemaker, conducting tissue, or contractile myocardial flaps ideal for transplantation. From studies in rats successful transplantation of thin constructs to the ventricle has been reported, but there remain further issues to resolve before larger human constructs will be available to test in the clinic.

  1. Cell therapy for diabetes mellitus: an opportunity for stem cells?

    PubMed

    Soria, B; Bedoya, F J; Tejedo, J R; Hmadcha, A; Ruiz-Salmerón, R; Lim, S; Martin, F

    2008-01-01

    Diabetes is a chronic disease characterized by a deficit in beta cell mass and a failure of glucose homeostasis. Both circumstances result in a variety of severe complications and an overall shortened life expectancy. Thus, diabetes represents an attractive candidate for cell therapy. Reversal of diabetes can be achieved through pancreas and islet transplantation, but shortage of donor organs has prompted an intensive search for alternative sources of beta cells. This achievement has stimulated the search for appropriate stem cell sources. Both embryonic and adult stem cells have been used to generate surrogate beta cells or otherwise restore beta cell functioning. In this regard, several studies have reported the generation of insulin-secreting cells from embryonic and adult stem cells that normalized blood glucose values when transplanted into diabetic animal models. Due to beta cell complexity, insulin-producing cells generated from stem cells do not possess all beta cell attributes. This indicates the need for further development of methods for differentiation and selection of completely functional beta cells. While these problems are overcome, diabetic patients may benefit from therapeutic strategies based on autologous stem cell therapies addressing late diabetic complications. In this article, we discuss the recent progress in the generation of insulin-producing cells from embryonic and adult stem cells, together with the challenges for the clinical use of diabetes stem cell therapy.

  2. Stem Cell Research and Health Education

    PubMed Central

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2009-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the embryonic form. Consequently, there is public confusion over the benefits currently being derived from the use of stem cells and what can potentially be expected from their use in the future. The health educator’s role is to give an unbiased account of the current state of stem cell research. This paper provides the groundwork by discussing the types of cells currently identified, their potential use, and some of the political and ethical pitfalls resulting from such use. PMID:19672471

  3. Cancer stem cells: mirage or reality?

    PubMed

    Gupta, Piyush B; Chaffer, Christine L; Weinberg, Robert A

    2009-09-01

    The similarities and differences between normal tissue stem cells and cancer stem cells (CSCs) have been the source of much contention, with some recent studies calling into question the very existence of CSCs. An examination of the literature indicates, however, that the CSC model rests on firm experimental foundations and that differences in the observed frequencies of CSCs within tumors reflect the various cancer types and hosts used to assay these cells. Studies of stem cells and the differentiation program termed the epithelial-mesenchymal transition (EMT) point to the possible existence of plasticity between stem cells and their more differentiated derivatives. If present, such plasticity would have major implications for the CSC model and for future therapeutic approaches.

  4. Epithelial stem cells and intestinal cancer.

    PubMed

    Tan, Shawna; Barker, Nick

    2015-06-01

    The mammalian intestine is comprised of an epithelial layer that serves multiple functions in order to maintain digestive activity as well as intestinal homeostasis. This epithelial layer contains highly proliferative stem cells which facilitate its characteristic rapid regeneration. How these stem cells contribute to tissue repair and normal homeostasis are actively studied, and while we have a greater understanding of the molecular mechanisms and cellular locations that underlie stem cell regulation in this tissue, much still remains undiscovered. This review describes epithelial stem cells in both intestinal and non-intestinal tissues, as well as the strategies that have been used to further characterize the cells. Through a discussion of the current understanding of intestinal self-renewal and tissue regeneration in response to injury, we focus on how dysregulation of critical signaling pathways results in potentially oncogenic aberrations, and highlight issues that should be addressed in order for effective intestinal cancer therapies to be devised.

  5. Stem cell function and stress response are controlled by protein synthesis

    PubMed Central

    Blanco, Sandra; Bandiera, Roberto; Popis, Martyna; Hussain, Shobbir; Lombard, Patrick; Aleksic, Jelena; Sajini, Abdulrahim; Tanna, Hinal; Cortés-Garrido, Rosana; Gkatza, Nikoletta; Dietmann, Sabine; Frye, Michaela

    2016-01-01

    Summary Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here, we show that skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumourigenesis. Mechanistically we show that inhibition of post-transcriptional cytosine-5 methylation locks stem cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour. PMID:27306184

  6. Human embryonic stem cells and lung regeneration.

    PubMed

    Varanou, A; Page, C P; Minger, S L

    2008-10-01

    Human embryonic stem cells are pluripotent cells derived from the inner cell mass of preimplantation stage embryos. Their unique potential to give rise to all differentiated cell types has generated great interest in stem cell research and the potential that it may have in developmental biology, medicine and pharmacology. The main focus of stem cell research has been on cell therapy for pathological conditions with no current methods of treatment, such as neurodegenerative diseases, cardiac pathology, retinal dysfunction and lung and liver disease. The overall aim is to develop methods of application either of pure cell populations or of whole tissue parts to the diseased organ under investigation. In the field of pulmonary research, studies using human embryonic stem cells have succeeded in generating enriched cultures of type II pneumocytes in vitro. On account of their potential of indefinite proliferation in vitro, embryonic stem cells could be a source of an unlimited supply of cells available for transplantation and for use in gene therapy. Uncovering the ability to generate such cell types will expand our understanding of biological processes to such a degree that disease understanding and management could change dramatically.

  7. On the stem cell origin of cancer.

    PubMed

    Sell, Stewart

    2010-06-01

    In each major theory of the origin of cancer-field theory, chemical carcinogenesis, infection, mutation, or epigenetic change-the tissue stem cell is involved in the generation of cancer. Although the cancer type is identified by the more highly differentiated cells in the cancer cell lineage or hierarchy (transit-amplifying cells), the property of malignancy and the molecular lesion of the cancer exist in the cancer stem cell. In the case of teratocarcinomas, normal germinal stem cells have the potential to become cancers if placed in an environment that allows expression of the cancer phenotype (field theory). In cancers due to chemically induced mutations, viral infections, somatic and inherited mutations, or epigenetic changes, the molecular lesion or infection usually first occurs in the tissue stem cells. Cancer stem cells then give rise to transit-amplifying cells and terminally differentiated cells, similar to what happens in normal tissue renewal. However, the major difference between cancer growth and normal tissue renewal is that whereas normal transit amplifying cells usually differentiate and die, at various levels of differentiation, the cancer transit-amplifying cells fail to differentiate normally and instead accumulate (ie, they undergo maturation arrest), resulting in cancer growth.

  8. Stem cells and somatic cells: reprogramming and plasticity.

    PubMed

    Estrov, Zeev

    2009-01-01

    Recent seminal discoveries have significantly advanced the field of stem cell research and received worldwide attention. Improvements in somatic cell nuclear transfer (SCNT) technology, enabling the cloning of Dolly the sheep, and the derivation and differentiation of human embryonic stem cells raised hopes that normal cells could be generated to replace diseased or injured tissue. At the same time, in vitro and in vivo studies demonstrated that somatic cells of one tissue are capable of generating cells of another tissue. It was theorized that any cell might be reprogrammed, by exposure to a new environment, to become another cell type. This concept contradicts two established hypotheses: (1) that only specific tissues are generated from the endoderm, mesoderm, and ectoderm and (2) that tissue cells arise from a rare population of tissue-specific stem cells in a hierarchical fashion. SCNT, cell fusion experiments, and most recent gene transfer studies also contradict these hypotheses, as they demonstrate that mature somatic cells can be reprogrammed to regain pluripotent (or even totipotent) stem cell capacity. On the basis of the stem cell theory, hierarchical cancer stem cell differentiation models have been proposed. Cancer cell plasticity is an established phenomenon that supports the notion that cellular phenotype and function might be altered. Therefore, mechanisms of cellular plasticity should be exploited and the clinical significance of the cancer stem cell theory cautiously assessed.

  9. Stem cell systems and regeneration in planaria.

    PubMed

    Rink, Jochen C

    2013-03-01

    Planarians are members of the Platyhelminthes (flatworms). These animals have evolved a remarkable stem cell system. A single pluripotent adult stem cell type ("neoblast") gives rise to the entire range of cell types and organs in the planarian body plan, including a brain, digestive-, excretory-, sensory- and reproductive systems. Neoblasts are abundantly present throughout the mesenchyme and divide continuously. The resulting stream of progenitors and turnover of differentiated cells drive the rapid self-renewal of the entire animal within a matter of weeks. Planarians grow and literally de-grow ("shrink") by the food supply-dependent adjustment of organismal turnover rates, scaling body plan proportions over as much as a 50-fold size range. Their dynamic body architecture further allows astonishing regenerative abilities, including the regeneration of complete and perfectly proportioned animals even from tiny tissue remnants. Planarians as an experimental system, therefore, provide unique opportunities for addressing a spectrum of current problems in stem cell research, including the evolutionary conservation of pluripotency, the dynamic organization of differentiation lineages and the mechanisms underlying organismal stem cell homeostasis. The first part of this review focuses on the molecular biology of neoblasts as pluripotent stem cells. The second part examines the fascinating mechanistic and conceptual challenges posed by a stem cell system that epitomizes a universal design principle of biological systems: the dynamic steady state.

  10. Stem cell genome-to-systems biology.

    PubMed

    Chia, Na-Yu; Ng, Huck-Hui

    2012-01-01

    Stem cells are capable of extended proliferation and concomitantly differentiating into a plethora of specialized cell types that render them apropos for their usage as a form of regenerative medicine for cell replacement therapies. The molecular processes that underlie the ability for stem cells to self-renew and differentiate have been intriguing, and elucidating the intricacies within the genome is pertinent to enhance our understanding of stem cells. Systems biology is emerging as a crucial field in the study of the sophisticated nature of stem cells, through the adoption of multidisciplinary approaches which couple high-throughput experimental techniques with computational and mathematical analysis. This allows for the determination of the molecular constituents that govern stem cell characteristics and conjointly with functional validations via genetic perturbation and protein location binding analysis necessitate the construction of the complex transcriptional regulatory network. With the elucidation of protein-protein interaction, protein-DNA regulation, microRNA involvement as well as the epigenetic modifications, it is possible to comprehend the defining features of stem cells at the system level.

  11. Prion potency in stem cells biology.

    PubMed

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  12. Adult Stem Cell Therapy for Stroke: Challenges and Progress

    PubMed Central

    Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

    2016-01-01

    Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

  13. Cancer stem cell targeted therapy: progress amid controversies.

    PubMed

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-12-29

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy.

  14. Cancer stem cell targeted therapy: progress amid controversies

    PubMed Central

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  15. Regulation of breast cancer stem cell features.

    PubMed

    Czerwinska, Patrycja; Kaminska, Bozena

    2015-01-01

    Cancer stem cells (CSCs) are rare, tumour-initiating cells that exhibit stem cell properties: capacity of self-renewal, pluripotency, highly tumorigenic potential, and resistance to therapy. Cancer stem cells have been characterised and isolated from many cancers, including breast cancer. Developmental pathways, such as the Wnt/β-catenin, Notch/γ-secretase/Jagged, Shh (sonic hedgehog), and BMP signalling pathways, which direct proliferation and differentiation of normal stem cells, have emerged as major signalling pathways that contribute to the self-renewal of stem and/or progenitor cells in a variety of organs and cancers. Deregulation of these signalling pathways is frequently linked to an epithelial-mesenchymal transition (EMT), and breast CSCs often possess properties of cells that have undergone the EMT process. Signalling networks mediated by microRNAs and EMT-inducing transcription factors tie the EMT process to regulatory networks that maintain "stemness". Recent studies have elucidated epigenetic mechanisms that control pluripotency and stemness, which allows an assessment on how embryonic and normal tissue stem cells are deregulated during cancerogenesis to give rise to CSCs. Epigenetic-based mechanisms are reversible, and the possibility of "resetting" the abnormal cancer epigenome by applying pharmacological compounds targeting epigenetic enzymes is a promising new therapeutic strategy. Chemoresistance of CSCs is frequently driven by various mechanisms, including aberrant expression/activity of ABC transporters, aldehyde dehydrogenase and anti-oncogenic proteins (i.e. BCL2, B-cell lymphoma-2), enhanced DNA damage response, activation of pro-survival signalling pathways, and epigenetic deregulations. Despite controversy surrounding the CSC hypothesis, there is substantial evidence for their role in cancer, and a number of drugs intended to specifically target CSCs have entered clinical trials.

  16. Mesenchymal stem cells in regenerative rehabilitation

    PubMed Central

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-01-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future. PMID:27390452

  17. Ethical issues in stem cell research.

    PubMed

    Lo, Bernard; Parham, Lindsay

    2009-05-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson's disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies.

  18. Ethical Issues in Stem Cell Research

    PubMed Central

    Lo, Bernard; Parham, Lindsay

    2009-01-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies. PMID:19366754

  19. Mesenchymal stem cells in regenerative rehabilitation.

    PubMed

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-06-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient's medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future.

  20. FDA Warns About Stem Cell Claims

    MedlinePlus

    ... perpetrators who expose the American public to the dangers of unapproved stem cells and ensure that they ... You Need to Know More in Consumer Updates Animal & Veterinary Children's Health Cosmetics Dietary Supplements Drugs Food ...

  1. Becoming a Blood Stem Cell Donor

    MedlinePlus Videos and Cool Tools

    ... donors at http://www.marrow.org . Category Science & Technology License Standard YouTube License Show more Show less ... views 10:58 Susan Solomon: The promise of research with stem cells - Duration: 14:59. TED 61, ...

  2. Hematopoietic stem cell engineering at a crossroads.

    PubMed

    Rivière, Isabelle; Dunbar, Cynthia E; Sadelain, Michel

    2012-02-02

    The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.

  3. De Novo Kidney Regeneration with Stem Cells

    PubMed Central

    Yokote, Shinya; Yamanaka, Shuichiro; Yokoo, Takashi

    2012-01-01

    Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration. PMID:23251079

  4. Will embryonic stem cells change health policy?

    PubMed

    Sage, William M

    2010-01-01

    Embryonic stem cells are actively debated in political and public policy arenas. However, the connections between stem cell innovation and overall health care policy are seldom elucidated. As with many controversial aspects of medical care, the stem cell debate bridges to a variety of social conversations beyond abortion. Some issues, such as translational medicine, commercialization, patient and public safety, health care spending, physician practice, and access to insurance and health care services, are core health policy concerns. Other issues, such as economic development, technologic progress, fiscal politics, and tort reform, are only indirectly related to the health care system but are frequently seen through a health care lens. These connections will help determine whether the stem cell debate reaches a resolution, and what that resolution might be.

  5. Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study.

    PubMed

    Berger, Massimo; Lanino, Edoardo; Cesaro, Simone; Zecca, Marco; Vassallo, Elena; Faraci, Maura; De Bortoli, Massimiliano; Barat, Veronica; Prete, Arcangelo; Fagioli, Franca

    2016-05-01

    Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients.

  6. Generation of pluripotent stem cells from adult human testis.

    PubMed

    Conrad, Sabine; Renninger, Markus; Hennenlotter, Jörg; Wiesner, Tina; Just, Lothar; Bonin, Michael; Aicher, Wilhelm; Bühring, Hans-Jörg; Mattheus, Ulrich; Mack, Andreas; Wagner, Hans-Joachim; Minger, Stephen; Matzkies, Matthias; Reppel, Michael; Hescheler, Jürgen; Sievert, Karl-Dietrich; Stenzl, Arnulf; Skutella, Thomas

    2008-11-20

    Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

  7. Cell therapy using induced pluripotent stem cells or somatic stem cells: this is the question.

    PubMed

    Somoza, Rodrigo A; Rubio, Francisco J

    2012-05-01

    A lot of effort has been developed to bypass the use of embryonic stem cells (ES) in human therapies, because of several concerns and ethical issues. Some unsolved problems of using stem cells for human therapies, excluding the human embryonic origin, are: how to regulate cell plasticity and proliferation, immunological compatibility, potential adverse side-effects when stem cells are systemically administrated, and the in vivo signals to rule out a specific cell fate after transplantation. Currently, it is known that almost all tissues of an adult organism have somatic stem cells (SSC). Whereas ES are primary involved in the genesis of new tissues and organs, SSC are involved in regeneration processes, immuno-regulatory and homeostasis mechanisms. Although the differentiating potential of ES is higher than SSC, several studies suggest that some types of SSC, such as mesenchymal stem cells (MSC), can be induced epigenetically to differentiate into tissue-specific cells of different lineages. This unexpected pluripotency and the variety of sources that they come from, can make MSC-like cells suitable for the treatment of diverse pathologies and injuries. New hopes for cell therapy came from somatic/mature cells and the discovery that could be reprogrammed to a pluripotent stage similar to ES, thus generating induced pluripotent stem cells (iPS). For this, it is necessary to overexpress four main reprogramming factors, Sox2, Oct4, Klf4 and c-Myc. The aim of this review is to analyze the potential and requirements of cellular based tools in human therapy strategies, focusing on the advantage of using MSC over iPS.

  8. Matrix elasticity directs stem cell lineage specification

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2010-03-01

    Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. [4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).

  9. Mesenchymal stem cells: the fibroblasts’ new clothes?

    PubMed Central

    Haniffa, Muzlifah A.; Collin, Matthew P.; Buckley, Christopher D.; Dazzi, Francesco

    2009-01-01

    Mesenchymal stem cells are adherent stromal cells, initially isolated from the bone marrow, characterized by their ability to differentiate into mesenchymal tissues such as bone, cartilage and fat. They have also been shown to suppress immune responses in vitro. Because of these properties, mesenchymal stem cells have recently received a very high profile. Despite the dramatic benefits reported in early phase clinical trials, their functions remain poorly understood. Particularly, several questions remain concerning the origin of mesenchymal stem cells and their relationship to other stromal cells such as fibroblasts. Whereas clear gene expression signatures are imprinted in stromal cells of different anatomical origins, the anti-proliferative effects of mesenchymal stem cells and fibroblasts and their potential to differentiate appear to be common features between these two cell types. In this review, we summarize recent studies in the context of historical and often neglected stromal cell literature, and present the evidence that mesenchymal stem cells and fibroblasts share much more in common than previously recognized. PMID:19109217

  10. Stem Cell Therapy for the Inner Ear

    PubMed Central

    Okano, Takayuki

    2012-01-01

    In vertebrates, perception of sound, motion, and balance is mediated through mechanosensory hair cells located within the inner ear. In mammals, hair cells are only generated during a short period of embryonic development. As a result, loss of hair cells as a consequence of injury, disease, or genetic mutation, leads to permanent sensory deficits. At present, cochlear implantation is the only option for profound hearing loss. However, outcomes are still variable and even the best implant cannot provide the acuity of a biological ear. The recent emergence of stem cell technology has the potential to open new approaches for hair cell regeneration. The goal of this review is to summarize the current state of inner ear stem cell research from a viewpoint of its clinical application for inner ear disorders to illustrate how complementary studies have the potential to promote and refine stem cell therapies for inner ear diseases. The review initially discusses our current understanding of the genetic pathways that regulate hair cell formation from inner ear progenitors during normal development. Subsequent sections discuss the possible use of endogenous inner ear stem cells to induce repair as well as the initial studies aimed at transplanting stem cells into the ear. PMID:22514095

  11. Measuring the Aging Process in Stem Cells

    PubMed Central

    Liu, Yi; Van Zant, Gary; Liang, Ying

    2015-01-01

    Summary Stem cells persist in replenishing functional mature cells throughout life by self-renewal and multilineage differentiation. Hematopoietic stem cells (HSCs) are among the best-characterized and understood stem cells, and they are responsible for the life-long production of all lineages of blood cells. HSCs are a heterogeneous population containing lymphoid-biased, myeloid-biased and balanced subsets. HSCs undergo age-associated phenotypic and functional changes, and the composition of the HSC pool alters with aging. HSCs and their lineage-biased subfractions can be identified and analyzed by flow cytometry based on cell surface makers. Fluorescence-activated cell sorting (FACS) enables the isolation and purification of HSCs that greatly facilitates the mechanistic study of HSCs and their aging process at both cellular and molecular levels. The mouse model has been extensively used in HSC aging study. Bone marrow cells are isolated from young and old mice and stained with fluorescence-conjugated antibodies specific for differentiated and stem cells. HSCs are selected based on the negative expression of lineage markers and positive selection for several sets of stem cell markers. Lineage-biased HSCs can be further distinguished by the level of SLAM/CD150 expression and the extent of Hoechst efflux. PMID:25388383

  12. 3 CFR - Guidelines for Human Stem Cell Research

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the...

  13. Deriving blood stem cells from pluripotent stem cells for research and therapy.

    PubMed

    Daley, George Q

    2014-01-01

    Embryonic stem cells and induced pluripotent stem cells offer promise for research and treatment of hematologic diseases. While broad clinical application in humans is still a distant prospect, there are promising near-term applications in transfusion of platelets and red blood cells.

  14. Multiple myeloma cancer stem cells

    PubMed Central

    Gao, Minjie; Kong, Yuanyuan; Yang, Guang; Gao, Lu; Shi, Jumei

    2016-01-01

    Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contributes to disease relapse, but the mechanisms of drug resistance have not been fully understood. The major signaling pathways involved in the regulation of self-renewal and differentiation of MMSCs include Hedgehog (Hh), Wingless (Wnt), Notch and PI3K/Akt/mTOR. However, the precise role of these signaling pathways needs to be clarified. It has been reported that the microRNA profile of MMSCs is remarkably different than that of non-MMSCs. Therefore, the search for targeting MMSCs has also been focused on microRNAs. Complex and mutual interactions between the MMSC and the surrounding bone marrow (BM) microenvironment sustain self-renewal and survival of MMSC. However, the required molecules for the interaction of the MMSC and the surrounding BM microenvironment need to be further identified. In this review, we summarize the current state of knowledge of MMSCs regarding their phenotype, mechanisms of drug resistance, signaling pathways that regulate MMSCs self-renewal and differentiation, abnormal microRNAs expression, and their interactions with the BM microenvironment. PMID:27007154

  15. When stem cells grow old: phenotypes and mechanisms of stem cell aging

    PubMed Central

    Schultz, Michael B.; Sinclair, David A.

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. PMID:26732838

  16. Development in intracerebral stem cell grafts

    PubMed Central

    Reyes, Stephanny; Tajiri, Naoki; Borlongan, Cesar V.

    2015-01-01

    The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson’s disease, Huntington’s disease, stroke, and traumatic brain injury. PMID:25739415

  17. Mesenchymal stem cells show radioresistance in vivo.

    PubMed

    Singh, Sarvpreet; Kloss, Frank R; Brunauer, Regina; Schimke, Magdalena; Jamnig, Angelika; Greiderer-Kleinlercher, Brigitte; Klima, Günter; Rentenberger, Julia; Auberger, Thomas; Hächl, Oliver; Rasse, Michael; Gassner, Robert; Lepperdinger, Günter

    2012-04-01

    Irradiation impacts on the viability and differentiation capacity of tissue-borne mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. As a consequence of radiotherapy, bones may develop osteoradionecrosis. When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced. Mitotically stalled cells were still capable of differentiating into osteoblasts and pre-adipocytes. As a large animal model comparable to the clinical situation, pig mandibles were subjected to fractionized radiation of 2 χ 9 Gy within 1 week. This treatment mimics that of a standardized clinical treatment regimen of head and neck cancer patients irradiated 30 χ 2 Gy. In the pig model, fractures which had been irradiated, showed delayed osseous healing. When isolating MSC at different time points post-irradiation, no significant changes regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with a single dose of either 9 or 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first 2 weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can effectively cope with irradiation up to high doses in vivo. This finding should thus be implemented in future therapeutic concepts to protect regenerating tissue from radiation consequences.

  18. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  19. Perspectives and controversies in the field of stem cell research.

    PubMed

    Romano, Gaetano

    2006-09-01

    The fourth annual meeting of the International Society for Stem Cell Research focused on a number of pressing issues, including: (I) the need to better characterize the biology of stem cells; (II) the need to exploit and optimize the great therapeutic potential of stem cells in tissue regeneration; (III) ethical and safety considerations related to the use of human embryonic stem cells; (IV) the contribution of adult stem cells to carcinogenesis; (V) the need to investigate the biology of cancer stem cells. The purpose of this report is to summarize the current status of stem cell research, as surmised by the proceedings of this meeting.

  20. [Limbal stem cell deficiency management. A review].

    PubMed

    Kocaba, V; Damour, O; Auxenfans, C; Burillon, C

    2016-11-01

    Limbal stem cell deficiency is predominantly caused by severe eye burns resulting in a decreased or a complete ablation of the regenerative potential of these stem cells. The inability to reconstruct the corneal epithelium further leads conjunctivalization of the gimbal-epithelial barrier. These abnormalities collectively result in the progressive opacification of the cornea responsible for blindness that is driven by chronic corneal ulceration and neovascularization. The underlying pathology of the cornea affects the homeostasis of the neighboring conjunctiva, eyelids, and tear film. Therefore, the ocular reconstruction to treat limbal stem cell deficiency is quite prolonged and involves a continued treatment plan. The management of limbal stem cell deficiency has undergone a multitude of changes over the past several decades. The understanding of limbal anatomy and physiology, as well as therapeutic advances in the stem cell field have propelled the development of new treatments offering new hope to severely disabled patients. Cultivated limbal epithelial and oral mucosal epithelial transplantations are therefore viable alternatives that could be utilized for the treatment of limbal stem cell deficiency.

  1. Stem cell technologies: regulation, patents and problems.

    PubMed

    Then, Shih-Ning

    2004-11-01

    Human embryonic stem cell research promises to deliver in the future a whole range of therapeutic treatments, but currently governments in different jurisdictions must try to regulate this burgeoning area. Part of the problem has been, and continues to be, polarised community opinion on the use of human embryonic stem cells for research. This article compares the approaches of the Australian, United Kingdom and United States governments in regulating human embryonic stem cell research. To date, these governments have approached the issue through implementing legislation or policy to control research. Similarly, the three jurisdictions have viewed the patentability of human embryonic stem cell technologies in their own ways with different policies being adopted by the three patent offices. This article examines these different approaches and discusses the inevitable concerns that have been raised due to the lack of a universal approach in relation to the regulation of research; the patenting of stem cell technologies; and the effects patents granted are having on further human embryonic stem cell research.

  2. Building Epithelial Tissues from Skin Stem Cells

    PubMed Central

    Fuchs, E.; Nowak, J.A.

    2009-01-01

    The skin epidermis and its appendages provide a protective barrier that guards against loss of fluids, physical trauma, and invasion by harmful microbes. To perform these functions while confronting the harsh environs of the outside world, our body surface undergoes constant rejuvenation through homeostasis. In addition, it must be primed to repair wounds in response to injury. The adult skin maintains epidermal homeostasis, hair regeneration, and wound repair through the use of its stem cells. What are the properties of skin stem cells, when do they become established during embryogenesis, and how are they able to build tissues with such remarkably distinct architectures? How do stem cells maintain tissue homeostasis and repair wounds and how do they regulate the delicate balance between proliferation and differentiation? What is the relationship between skin cancer and mutations that perturbs the regulation of stem cells? In the past 5 years, the field of skin stem cells has bloomed as we and others have been able to purify and dissect the molecular properties of these tiny reservoirs of goliath potential. We report here progress on these fronts, with emphasis on our laboratory’s contributions to the fascinating world of skin stem cells. PMID:19022769

  3. Stem cell treatment for type 1 diabetes

    PubMed Central

    Li, Ming; Ikehara, Susumu

    2014-01-01

    Type 1 diabetes mellitus (T1DM) is a common chronic disease in children, characterized by a loss of β cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy, and retinopathy. Curative therapies mainly include diet and insulin administration. Although hyperglycemia can be improved by insulin administration, exogenous insulin injection cannot successfully mimic the insulin secretion from normal β cells, which keeps blood glucose levels within the normal range all the time. Islet and pancreas transplantation achieves better glucose control, but there is a lack of organ donors. Cell based therapies have also been attempted to treat T1DM. Stem cells such as embryonic stem cells, induced pluripotent stem cells and tissue stem cells (TSCs) such as bone marrow-, adipose tissue-, and cord blood-derived stem cells, have been shown to generate insulin-producing cells. In this review, we summarize the most-recently available information about T1DM and the use of TSCs to treat T1DM. PMID:25364717

  4. Apoptosis, stem cells, and tissue regeneration.

    PubMed

    Bergmann, Andreas; Steller, Hermann

    2010-10-26

    Most metazoans have at least some ability to regenerate damaged cells and tissues, although the regenerative capacity varies depending on the species, organ, or developmental stage. Cell replacement and regeneration occur in two contexts: renewal of spent cells during tissue homeostasis (homeostatic growth), and in response to external injury, wounding, or amputation (epimorphic regeneration). Model organisms that display remarkable regenerative capacity include amphibians, planarians, Hydra, and the vertebrate liver. In addition, several mammalian organs--including the skin, gut, kidney, muscle, and even the human nervous system--have some ability to replace spent or damaged cells. Although the regenerative response is complex, it typically involves the induction of new cell proliferation through formation of a blastema, followed by cell specification, differentiation, and patterning. Stem cells and undifferentiated progenitor cells play an important role in both tissue homeostasis and tissue regeneration. Stem cells are typically quiescent or passing slowly through the cell cycle in adult tissues, but they can be activated in response to cell loss and wounding. A series of studies, mostly performed in Drosophila as well as in Hydra, Xenopus, and mouse, has revealed an unexpected role of apoptotic caspases in the production of mitogenic signals that stimulate the proliferation of stem and progenitor cells to aid in tissue regeneration. This Review summarizes some of the key findings and discusses links to stem cell biology and cancer.

  5. Current overview on dental stem cells applications in regenerative dentistry

    PubMed Central

    Bansal, Ramta; Jain, Aditya

    2015-01-01

    Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental stem cells were shortlisted and the facts are compiled. The objective of this review article is to discuss the history of stem cells, different stem cells relevant for dentistry, their isolation approaches, collection, and preservation of dental stem cells along with the current status of dental and medical applications. PMID:25810631

  6. Limbal stem cell transplantation: current perspectives

    PubMed Central

    Atallah, Marwan Raymond; Palioura, Sotiria; Perez, Victor L; Amescua, Guillermo

    2016-01-01

    Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD). In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers

  7. European stem cell research in legal shackles.

    PubMed

    Nielen, Myrthe G; de Vries, Sybe A; Geijsen, Niels

    2013-12-11

    Advances in stem cell biology have raised legal challenges to the patentability of stem cells and any derived technologies and processes. In 1999, Oliver Brüstle was granted a patent for the generation and therapeutic use of neural cells derived from human embryonic stem cells (hESCs). The patent was challenged and put before the European Court of Justice, which ruled that inventions involving the prior destruction of human embryos cannot be patented. The legal maneuvering around this case demonstrates that the future of stem cell-based patents in Europe remains unsettled. Furthermore, owing to the European Court's broad definition of hESC as 'any cell that is capable of commencing development into a human being,' novel technologies that could eliminate the need for hESCs, such as induced pluripotent stem cells (iPSCs), are at risk of being included under the same ruling. Advances in the in vitro development of germ cells from pluripotent stem cells may one day provide a direct developmental path from iPSC to oocyte and sperm, and, according to the European Court's reasoning, legally equate iPSCs with human embryos. In this review, we will briefly discuss the Brüstle v Greenpeace case and the implications of the European Court of Justice's ruling. We will identify potential risks for stem cell research and future therapeutics resulting from the broad legal definition of the human embryo. Finally, we will broach the current legal landscape, as this broad definition has also created great uncertainty about the status of human iPSCs.

  8. Ewing's sarcoma cancer stem cell targeted therapy.

    PubMed

    Todorova, Roumiana

    2014-01-01

    Ewing`s sarcoma (ES) family of tumors (ESFTs) are round cell tumors of bone and soft tissues, afflicting children and young adults. This review summarizes the present findings about ES cancer stem cell (CSC) targeted therapy: prognostic factors, chromosomal translocations, initiation, epigenetic mechanisms, candidate cell of ES origin (Mesenchymal stem cells (MSCs) and Neural crest stem cells (NCSCs)). The ES CSC model, histopathogenesis, histogenesis, pathogenesis, ES mediated Hematopoietic stem progenitor cells (HSPCs) senescence are also discussed. ESFTs therapy is reviewed concerning CSCs, radiotherapy, risk of subsequent neoplasms, stem cell (SC) support, promising therapeutic targets for ES CSCs (CSC markers, immune targeting, RNAi phenotyping screens, proposed new drugs), candidate EWS-FLI1 target genes and further directions (including human embryonic stem cells (hESCs)). Bone marrow-derived human MSCs are permissive for EWS-FLI1 expression with transition to ESFT-like cellular phenotype. ESFTs are genetically related to NCSC, permissive for EWS-FLI1 expression and susceptible to oncogene-induced immortalization. Primitive neuroectodermal features and MSC origin of ESFTs provide a basis of immune targeting. The microRNAs profile of ES CSCs is shared by ESCs and CSCs from divergent tumor types. Successful reprogramming of differentiated human somatic cells into a pluripotent state allows creation of patient- and disease-specific SCs. The functional role of endogenous EWS at stem cell level on both senescence and tumorigenesis is a link between cancer and aging. The regulatory mechanisms of oncogenic activity of EWS fusions could provide new prognostic biomarkers, therapeutic opportunities and tumor-specific anticancer agents against ESFTs.

  9. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks

    PubMed Central

    Liu, Suling; Ginestier, Christophe; Ou, Sing J.; Clouthier, Shawn G.; Patel, Shivani H.; Monville, Florence; Korkaya, Hasan; Heath, Amber; Dutcher, Julie; Kleer, Celina G.; Jung, Younghun; Dontu, Gabriela; Taichman, Russell; Wicha, Max S.

    2011-01-01

    We have utilized in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSCs) and bone marrow derived mesenchymal stem cells (MSCs). We demonstrate that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase (ALDH) expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerate tumor growth by increasing the breast cancer stem cell population. Utilizing immunochemistry, we identified “MSC-CSC niches” in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow derived mesenchymal stem cell may accelerate human breast tumor growth by generating cytokine networks that regulate the cancer stem cell population. PMID:21224357

  10. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking

    PubMed Central

    Ratajczak, M Z

    2015-01-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  11. Epidermal stem cells: interactions in developmental environments.

    PubMed

    Bickenbach, Jackie R; Grinnell, Katie L

    2004-10-01

    Homeostasis of continuously renewing adult tissues, such as the epidermis of the skin, is maintained by epidermal stem cells (EpiSC), which are a small population of undifferentiated, self-renewing basal keratinocyte cells that produce daughter transit amplifying (TA) cells to make up the majority of the proliferative basal cell population in the epidermis. We have isolated EpiSC from neonatal and adult skin, and shown that these cells can regenerate an epidermis that lasts long term in vitro and in vivo, and that permanently expresses a recombinant gene in the regenerated tissue (Bickenbach and Dunnwald, 2000; Dunnwald et al., 2001). When we injected murine EpiSC into the developing blastocyst environment of the mouse, we found that both neonatal and adult EpiSC retained some ability to participate in the formation of tissues from all three germ layers (Liang and Bickenbach, 2002; Bickenbach and Chinnathambi, 2004; Liang et al., 2004). Although it appears evident that EpiSC act as pluripotent stem cells, how this reprogramming takes place is not understood. EpiSC might directly transdifferentiate into other cell types or they might first dedifferentiate into a more primitive cell type, and then proceed to develop along a cell lineage pathway. To begin to unravel this, we co-cultured EpiSC with embryonic stem (ES) cells, and found that EpiSC could alter their cell lineage protein expression to that of a more primitive cell type. We also placed EpiSC in a wounded environment and found that EpiSC interacted with the mesenchymal cells repopulating the wound bed. Our findings indicate that the population of cells that we isolate as EpiSC has a pluripotent capability. This has led us to postulate a paradigm shift for somatic stem cells. We propose that tissues maintain a sequestered population of uncommitted stem cells that retain a regenerative response which is enhanced when the cells are exposed to developmental or stress influences.

  12. Spheroid Culture of Mesenchymal Stem Cells

    PubMed Central

    Cesarz, Zoe; Tamama, Kenichi

    2016-01-01

    Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown. PMID:26649054

  13. Bone marrow stromal stem cells: nature, biology, and potential applications.

    PubMed

    Bianco, P; Riminucci, M; Gronthos, S; Robey, P G

    2001-01-01

    Bone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes. In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use. Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy.

  14. Adipose stem cells and skin repair.

    PubMed

    Jeong, Jae Ho

    2010-06-01

    With the discovery of adipose stem cells (ASCs), 40 years after the identification of bone marrow stem cells, a new era of active stem cell therapy has opened. The abundance of stem cells harvested from adipose tissue enables us to instantly apply primary cells without culture expansion. ASCs are already clinically applied in many other purposes such as cell-enriched lipotransfer, wound healing, skin rejuvenation, scar remodeling and skin tissue engineering. Although cellular mechanism of ASCs is not completely understood, recent researches have disclosed some of their unique functions as mesenchymal stem cells. There have been increasing numbers of scientific reports on the therapeutic effect of ASCs on skin repair, scar remodeling and rejuvenation. Wound healing and scar remodeling are complex, multi-cellular processes that involve coordinated efforts of many cell types and various cytokines. Recent reports showed ASCs as a powerful source of skin regeneration because of their capability to provide not only cellular elements, but also numerous cytokines. Currently, other attractive functions of ASCs in the recovery of extrinsic aging and radiation damage are under active investigation. It seems that autologous ASCs have great promise for applications in repair of skin, rejuvenation of aging skin and aging-related skin lesions. This review will focus on the specific roles of ASCs in skin tissue, especially related with wound healing, radiation injury, scar remodeling, skin rejuvenation and skin engineering.

  15. Genome integrity, stem cells and hyaluronan

    PubMed Central

    Darzynkiewicz, Zbigniew; Balazs, Endre A.

    2012-01-01

    Faithful preservation of genome integrity is the critical mission of stem cells as well as of germ cells. Reviewed are the following mechanisms involved in protecting DNA in these cells: (a) The efflux machinery that can pump out variety of genotoxins in ATP-dependent manner; (b) the mechanisms maintaining minimal metabolic activity which reduces generation of reactive oxidants, by-products of aerobic respiration; (c) the role of hypoxic niche of stem cells providing a gradient of variable oxygen tension; (d) (e) the presence of hyaluronan (HA) and HA receptors on stem cells and in the niche; (f) the role of HA in protecting DNA from oxidative damage; (g) the specific function of HA in protecting DNA in stem cells; (h) the interactions of HA with sperm cells and oocytes that also may shield their DNA from oxidative damage, and (e) mechanisms by which HA exerts the anti-oxidant activity. While HA has multitude of functions its anti-oxidant capabilities are often overlooked but may be of significance in preservation of integrity of stem and germ cells genome. PMID:22383371

  16. Out of Eden: Stem Cells and Their Niches

    NASA Astrophysics Data System (ADS)

    Watt, Fiona M.; Hogan, Brigid L. M.

    2000-02-01

    Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. Both intrinsic and extrinsic signals regulate stem cell fate and some of these signals have now been identified. Certain aspects of the stem cell microenvironment, or niche, are conserved between tissues, and this can be exploited in the application of stem cells to tissue replacement therapy.

  17. Generation of parthenogenetic induced pluripotent stem cells from parthenogenetic neural stem cells.

    PubMed

    Do, Jeong Tae; Joo, Jin Young; Han, Dong Wook; Araúzo-Bravo, Marcos J; Kim, Min Jung; Greber, Boris; Zaehres, Holm; Sobek-Klocke, Ingeborg; Chung, Hyung Min; Schöler, Hans R

    2009-12-01

    Somatic cells can achieve a pluripotent cell state in a process called pluripotential reprogramming. Multipotent stem cells can differentiate into cells of only one lineage, but pluripotent stem cells can give rise to cells of all three germ layers of an organism. In this study, we generated induced pluripotent stem (iPS) cells from bimaternal (uniparental) parthenogenetic neural stem cells (pNSCs) by transduction with either four (4F: Oct4, Klf4, Sox2, and c-Myc) or two (2F: Oct4 and Klf4) transcription factors. The resultant maternal iPS cells, which were reprogrammed directly from pNSCs, were capable of generating germ line-competent chimeras. Interestingly, analysis of global gene expression and imprinting status revealed that parthenogenetic iPS cells clustered closer to parthenogenetic ESCs than to female ESCs, with patterns that were clearly distinct from those of pNSCs.

  18. The bioethics of stem cell research and therapy

    PubMed Central

    Hyun, Insoo

    2010-01-01

    Discussion of the bioethics of human stem cell research has transitioned from controversies over the source of human embryonic stem cells to concerns about the ethical use of stem cells in basic and clinical research. Key areas in this evolving ethical discourse include the derivation and use of other human embryonic stem cell–like stem cells that have the capacity to differentiate into all types of human tissue and the use of all types of stem cells in clinical research. Each of these issues is discussed as I summarize the past, present, and future bioethical issues in stem cell research. PMID:20051638

  19. The Drosophila cyst stem cell lineage

    PubMed Central

    Zoller, Richard; Schulz, Cordula

    2012-01-01

    In all animals, germline cells differentiate in intimate contact with somatic cells and interactions between germline and soma are particularly important for germline development and function. In the male gonad of Drosophila melanogaster, the developing germline cells are enclosed by somatic cyst cells. The cyst cells are derived from cyst stem cells (CySCs) of somatic origin and codifferentiate with the germline cells. The fast generation cycle and the genetic tractability of Drosophila has made the Drosophila testis an excellent model for studying both the roles of somatic cells in guiding germline development and the interdependence of two separate stem cell lineages. This review focuses on our current understanding of CySC specification, CySC self-renewing divisions, cyst cell differentiation, and soma-germline interactions. Many of the mechanisms guiding these processes in Drosophila testes are similarly essential for the development and function of tissues in other organisms, most importantly for gametogenesis in mammals. PMID:23087834

  20. Hematopoietic stem cells as a tool for the treatment of glioblastoma multiforme

    PubMed Central

    Bryukhovetskiy, Igor S.; Dyuizen, Inessa V.; Shevchenko, Valeriy E.; Bryukhovetskiy, Andrey S.; Mischenko, Polina V.; Milkina, Elena V.; Khotimchenko, Yuri S.

    2016-01-01

    Glioblastoma multiforme is an aggressive malignant brain tumor with terminal consequences. A primary reason for its resistance to treatment is associated with cancer stem cells (CSCs), of which there are currently no effective ways to destroy. It remains unclear what cancer cells become a target of stem cell migration, what the role of this process is in oncogenesis and what stem cell lines should be used in developing antitumor technologies. Using modern post-genome technologies, the present study investigated the migration of human stem cells to cancer cells in vitro, the comparative study of cell proteomes of certain stem cells (including CSCs) was conducted and stem cell migration in vivo was examined. Of all glioblastoma cells, CSCs have the stability to attract normal stem cells. Critical differences in cell proteomes allow the consideration of hematopoietic stem cells (HSCs) as an instrument for interaction with glioblastoma CSCs. Following injection into the bloodstream of animals with glioblastoma, the majority of HSCs migrated to the tumor-containing brain hemisphere and penetrated the tumor tissue. HSCs therefore are of potential use in the development of methods to target CSCs. PMID:27748891

  1. Personalized nanomedicine advancements for stem cell tracking☆

    PubMed Central

    Janowski, Mirek; Bulte, Jeff W.M.; Walczak, Piotr

    2012-01-01

    Recent technological developments in biomedicine have facilitated the generation of data on the anatomical, physiological and molecular level for individual patients and thus introduces opportunity for therapy to be personalized in an unprecedented fashion. Generation of patient-specific stem cells exemplifies the efforts toward this new approach. Cell-based therapy is a highly promising treatment paradigm; however, due to the lack of consistent and unbiased data about the fate of stem cells in vivo, interpretation of therapeutic remains challenging hampering the progress in this field. The advent of nanotechnology with a wide palette of inorganic and organic nanostructures has expanded the arsenal of methods for tracking transplanted stem cells. The diversity of nanomaterials has revolutionized personalized nanomedicine and enables individualized tailoring of stem cell labeling materials for the specific needs of each patient. The successful implementation of stem cell tracking will likely be a significant driving force that will contribute to the further development of nanotheranostics. The purpose of this review is to emphasize the role of cell tracking using currently available nanoparticles. PMID:22820528

  2. In Utero Haematopoietic Stem Cell Transplantation (IUHSCT)

    PubMed Central

    Renda, Maria Concetta; Maggio, Aurelio

    2009-01-01

    In utero haematopoietic stem cell transplantation (IUHSCT) is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell chimerism has not been achieved. There are three possible barriers to engraftment following IUHSCT: limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient. PMID:21415998

  3. In Utero Haematopoietic Stem Cell Transplantation (IUHSCT).

    PubMed

    Renda, Maria Concetta; Maggio, Aurelio

    2009-12-29

    In utero haematopoietic stem cell transplantation (IUHSCT) is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell chimerism has not been achieved. There are three possible barriers to engraftment following IUHSCT: limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient.

  4. The kynurenine pathway in stem cell biology.

    PubMed

    Jones, Simon P; Guillemin, Gilles J; Brew, Bruce J

    2013-09-15

    The kynurenine pathway (KP) is the main catabolic pathway of the essential amino acid tryptophan. The KP has been identified to play a critical role in regulating immune responses in a variety of experimental settings. It is also known to be involved in several neuroinflammatory diseases including Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. This review considers the current understanding of the role of the KP in stem cell biology. Both of these fundamental areas of cell biology have independently been the focus of a burgeoning research interest in recent years. A systematic review of how the two interact has not yet been conducted. Several inflammatory and infectious diseases in which the KP has been implicated include those for which stem cell therapies are being actively explored at a clinical level. Therefore, it is highly relevant to consider the evidence showing that the KP influences stem cell biology and impacts the functional behavior of progenitor cells.

  5. Cancer stem cells: controversies in multiple myeloma.

    PubMed

    Brennan, Sarah K; Matsui, William

    2009-11-01

    Increasing data suggest that the initiation, relapse, and progression of human cancers are driven by specific cell populations within an individual tumor. However, inconsistencies have emerged in precisely defining phenotypic markers that can reliably identify these "cancer stem cells" in nearly every human malignancy studied to date. Multiple myeloma, one of the first tumors postulated to be driven by a rare population of cancer stem cells, is no exception. Similar to other diseases, controversy surrounds the exact phenotype and biology of multiple myeloma cells with the capacity for clonogenic growth. Here, we review the studies that have led to these controversies and discuss potential reasons for these disparate findings. Moreover, we speculate how these inconsistencies may be resolved through studies by integrating advancements in both myeloma and stem cell biology.

  6. Translating Stem Cell Biology Into Drug Discovery

    PubMed Central

    Singeç, Ilyas; Simeonov, Anton

    2016-01-01

    Pluripotent stem cell research has made extraordinary progress over the last decade. The robustness of nuclear reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has created entirely novel opportunities for drug discovery and personalized regenerative medicine. Patient- and disease-specific iPSCs can be expanded indefinitely and differentiated into relevant cell types of different organ systems. As the utilization of iPSCs is becoming a key enabling technology across various scientific disciplines, there are still important challenges that need to be addressed. Here we review the current state and reflect on the issues that the stem cell and translational communities are facing in bringing iPSCs closer to clinical application. PMID:27774310

  7. Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

    PubMed

    Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

    2014-01-01

    The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

  8. Germ line, stem cells, and epigenetic reprogramming.

    PubMed

    Surani, M A; Durcova-Hills, G; Hajkova, P; Hayashi, K; Tee, W W

    2008-01-01

    The germ cell lineage has the unique attribute of generating the totipotent state. Development of blastocysts from the totipotent zygote results in the establishment of pluripotent primitive ectoderm cells in the inner cell mass of blastocysts, which subsequently develop into epiblast cells in postimplantation embryos. The germ cell lineage in mice originates from these pluripotent epiblast cells of postimplantation embryos in response to specific signals. Pluripotent stem cells and unipotent germ cells share some fundamental properties despite significant phenotypic differences between them. Additionally, early primordial germ cells can be induced to undergo dedifferentiation into pluripotent embryonic germ cells. Investigations on the relationship between germ cells and pluripotent stem cells may further elucidate the nature of the pluripotent state. Furthermore, comprehensive epigenetic reprogramming of the genome in early germ cells, including extensive erasure of epigenetic modifications, is a critical step toward establishment of totipotency. The mechanisms involved may be relevant for gaining insight into events that lead to reprogramming of somatic cells into pluripotent stem cells.

  9. Totipotent migratory stem cells in a hydroid.

    PubMed

    Müller, Werner A; Teo, Regina; Frank, Uri

    2004-11-01

    Hydroids, members of the most ancient eumetazoan phylum, the Cnidaria, harbor multipotent, migratory stem cells lodged in interstitial spaces of epithelial cells and are therefore referred to as interstitial cells or i-cells. According to traditional understanding, based on studies in Hydra, these i-cells give rise to several cell types such as stinging cells, nerve cells, and germ cells, but not to ectodermal and endodermal epithelial cells; these are considered to constitute separate cell lineages. We show here that, in Hydractinia, the developmental potential of these migratory stem cells is wider than previously anticipated. We eliminated the i-cells from subcloned wild-type animals and subsequently introduced i-cells from mutant clones and vice versa. The mutant donors and the wild-type recipients differed in their sex, growth pattern, and morphology. With time, the recipient underwent a complete conversion into the phenotype and genotype of the donor. Thus, under these experimental conditions the interstitial stem cells of Hydractinia exhibit totipotency.

  10. Regulation of germ line stem cell homeostasis

    PubMed Central

    Garcia, T.X.; Hofmann, M.C.

    2015-01-01

    Mammalian spermatogenesis is a complex process in which spermatogonial stem cells of the testis (SSCs) develop to ultimately form spermatozoa. In the seminiferous epithelium, SSCs self-renew to maintain the pool of stem cells throughout life, or they differentiate to generate a large number of germ cells. A balance between SSC self-renewal and differentiation is therefore essential to maintain normal spermatogenesis and fertility. Stem cell homeostasis is tightly regulated by signals from the surrounding microenvironment, or SSC niche. By physically supporting the SSCs and providing them with these extrinsic molecules, the Sertoli cell is the main component of the niche. Earlier studies have demonstrated that GDNF and CYP26B1, produced by Sertoli cells, are crucial for self-renewal of the SSC pool and maintenance of the undifferentiated state. Down-regulating the production of these molecules is therefore equally important to allow germ cell differentiation. We propose that NOTCH signaling in Sertoli cells is a crucial regulator of germ cell fate by counteracting these stimulatory factors to maintain stem cell homeostasis. Dysregulation of this essential niche component can lead by itself to sterility or facilitate testicular cancer development.

  11. Induction of cancer cell stemness by chemotherapy.

    PubMed

    Hu, Xingwang; Ghisolfi, Laura; Keates, Andrew C; Zhang, Jian; Xiang, Shuanglin; Lee, Dong-ki; Li, Chiang J

    2012-07-15

    Recent studies indicate that cancer stem cells (CSCs) exist in most hematological and solid tumors. CSCs are characterized by their ability to self-renew and their capacity to differentiate into the multitude of cells that comprise the tumor mass. Moreover, these cells have been shown to be intrinsically resistant to conventional anticancer therapies. Despite their fundamental role in cancer pathogenesis, the cellular origin of CSCs remains highly controversial. The aim of this study was to examine whether heterogeneous cancer cells can acquire stem cell-like properties in response to chemotherapy. We demonstrate that carboplatin can induce the self-renewal (spherogenesis) and pluripotency (Sox2 and Oct3/4 expression) of hepatocellular carcinoma (HCC) cells grown under stem cell culture conditions. Moreover, we show that non-CSC cells, obtained by side population flow cytometric sorting using Hoechst 33342, can acquire stem-like properties after exposure to carboplatin. Finally, we show that knockdown of Sox2 and Oct3/4 gene expression in HCC cells can reduce carboplatin-mediated increases in sphere formation and increase cellular sensitivity to chemotherapy. Taken together, our data indicate that bulk cancer cells may be an important source of CSCs during tumor development, and that targeting Sox2 and/or Oct3/4 may be a promising approach for targeting CSCs in clinical cancer treatment.

  12. Nonlinear dynamics, Waddington landscape and stem cells

    NASA Astrophysics Data System (ADS)

    Tang, Chao

    There are hundreds of different cell types (skin, neuron, muscle, etc.) in human body, all derived from the stem cell and all have the same genetic information. About 60 years ago, Waddington speculated that the different cell types correspond to different minima in a landscape emerged from genetic interactions. Recently, biologists succeeded in transforming one cell type to another by perturbing the genetic interactions in a cell. I will discuss the experiments and a mathematical model of a set of such cell type transformations in mice, in which we can see an actual example of the Waddington landscape and ways to alter it to facilitate cell type transformation - in particular, to reprogram a differentiated cell back into a stem cell.

  13. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency

    NASA Astrophysics Data System (ADS)

    Boadi, J.; Sangwal, V.; MacNeil, S.; Matcher, S. J.

    2015-03-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells is continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. Limbal Stem Cell Deficiency (LSCD), in which the stem cell population is depleted, can lead to blindness. LSCD can be caused by chemical and thermal burns to the eye. A popular treatment, especially in emerging economies such as India, is the transplantation of limbal stem cells onto damaged limbus with hope of repopulating the region. Hence regenerating the corneal epithelium. In order to gain insights into the success rates of this treatment, new imaging technologies are needed in order to track the transplanted cells. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images of the retina. A custom OCT system has been built to image the corneal surface, to investigate the fate of transplanted limbal stem cells. We evaluate two methods to label and track transplanted cells: melanin labelling and magneto-labelling. To evaluate melanin labelling, stem cells are loaded with melanin and then transplanted onto a rabbit cornea denuded of its epithelium. The melanin displays strongly enhanced backscatter relative to normal cells. To evaluate magneto-labelling the stem cells are loaded with magnetic nanoparticles (20-30nm in size) and then imaged with a custom-built, magneto-motive OCT system.

  14. The Genetic and Epigenetic Journey of Embryonic Stem Cells into Mature Neural Cells

    PubMed Central

    Olynik, Brendan M.; Rastegar, Mojgan

    2012-01-01

    Epigenetic changes occur throughout life from embryonic development into adulthood. This results in the timely expression of developmentally important genes, determining the morphology and identity of different cell types and tissues within the body. Epigenetics regulate gene expression and cellular morphology through multiple mechanisms without alteration in the underlying DNA sequences. Different epigenetic mechanisms include chromatin condensation, post-translational modification of histone proteins, DNA cytosine marks, and the activity of non-coding RNA molecules. Epigenetics play key roles in development, stem cell differentiation, and have high impact in human disease. In this review, we will discuss our current knowledge about these epigenetic mechanisms, with a focus on histone and DNA marks. We will then talk about the genetics and epigenetics of embryonic stem cell self-renewal and differentiation into neural stem cells, and further into specific neuronal cell types. PMID:22629283

  15. Major complications following hematopoietic stem cell transplantation.

    PubMed

    Afessa, Bekele; Peters, Steve G

    2006-06-01

    Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) annually, 15 to 40% of whom are admitted to the intensive care unit. Pulmonary complications are the most life threatening conditions that develop in HSCT recipients. Both infectious and noninfectious complications occur more frequently in allogeneic HSCT. The management of HSCT recipients requires knowledge of their immune status, appropriate diagnostic evaluation, and early treatment. During the pre-engraftment phase (0 to 30 days after transplant), the most prevalent pathogens causing infection are bacteria and Candida species and, if the neutropenia persists, Aspergillus species. The early post-engraftment phase (30 to 100 days) is characterized by cytomegalovirus (CMV), Pneumocystis jiroveci, and Aspergillus infections. During the late posttransplant phase (> 100 days), allogeneic HSCT recipients are at risk for CMV, community-acquired respiratory virus, and encapsulated bacterial infections. Antigen and polymerase chain reaction assays are important for the diagnosis of CMV and Aspergillus infections. Diffuse alveolar hemorrhage (DAH) and peri-engraftment respiratory distress syndrome occur in both allogeneic and autologous HSCT recipients, usually during the first 30 days. Bronchiolitis obliterans occurs exclusively in allogeneic HSCT recipients with graft versus host disease. Idiopathic pneumonia syndrome occurs at any time following transplant. Bronchoscopy is usually helpful for the diagnosis of the infectious pulmonary complications and DAH.

  16. Clonal Evolution of Stem Cells in the Gastrointestinal Tract.

    PubMed

    Fink, Juergen; Koo, Bon-Kyoung

    The field of gastrointestinal epithelial stem cells is a rapidly developing area of adult stem cell research. The discovery of Lgr5(+) intestinal stem cells has enabled us to study many hidden aspects of the biology of gastrointestinal adult stem cells. Marked by Lgr5 and Troy, several novel endodermal stem cells have been identified in the gastrointestinal tract. A precise working model of stem cell propagation, dynamics, and plasticity has been revealed by a genetic labeling method, termed lineage tracing. This chapter introduces the reidentification of crypt base columnar cells as Lgr5(+) stem cells in the intestine. Subsequently, it will discuss dynamic clonal evolution and cellular plasticity in the intestinal stem cell zone, as well as in stem cell zones of stomach glands.

  17. Stem cells and applications: a survey.

    PubMed

    Stoltz, J-F; Bensoussan, D; Zhang, L; Decot, V; De Isla, N; Li, Y P; Huselstein, C; Benkirane-Jessel, N; Li, N; Reppel, L; He, Y; Li, Y Y

    2015-01-01

    Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been increasing interest in the study of undifferentiated progenitors that have ability to proliferate and differentiate in different tissues. Different stem cells (SC) with different potential can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult stem cells provide a more interesting approach to clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue or MSC of Wharton Jelly, which have limited potential, are of interest for clinical applications in regenerative medicine because they are easily separated and prepared and no ethical problems are involved in their use.During the last 10 years, these multipotent cells have generated considerable interest and in particular have been shown to escape allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study (cardiac insufficiency, atherosclerosis, stroke, bone, cartilage, diabetes, ophthalmology, urology, liver, organ's reconstruction…).

  18. Social media & stem cell science: examining the discourse.

    PubMed

    Adams, Amy; Lomax, Geoffrey; Santarini, Anthony

    2011-11-01

    Research suggests that the representation of scientific and medical issues in the traditional media such as newspapers, TV and radio is an important determinant of public opinion and related public policy outcomes, particularly with regard to attitudes toward stem cell research. With the emergence of social media, the discursive space around public policy issues has expanded to include a new demographic of media consumer who is directly involved in political action. However, little is known about the influence of social media on scientific public policy conversations. We analyzed Twitter posts on two topics relating to stem cell science and policy according to the originator and tone of the tweet, and whether the tweet was intended to be neutral or to further a stated policy position. This analysis provides a means for clarifying the role of social media in influencing public opinion of policy issues such as stem cell research and offers organizations a better understanding of how to more effectively apply social media to advancing their stem cell policy positions.

  19. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis

    PubMed Central

    North, Trista E.; Goessling, Wolfram; Walkley, Carl R.; Lengerke, Claudia; Kopani, Kamden R.; Lord, Allegra M.; Weber, Gerhard J.; Bowman, Teresa V.; Jang, Il-Ho; Grosser, Tilo; FitzGerald, Garret A.; Daley, George Q.; Orkin, Stuart H.; Zon, Leonard I.

    2009-01-01

    Haematopoietic stem cell (HSC) homeostasis is tightly controlled by growth factors, signalling molecules and transcription factors. Definitive HSCs derived during embryogenesis in the aorta-gonad-mesonephros region subsequently colonize fetal and adult haematopoietic organs1,2. To identify new modulators of HSC formation and homeostasis, a panel of biologically active compounds was screened for effects on stem cell induction in the zebrafish aorta-gonad-mesonephros region. Here, we show that chemicals that enhance prostaglandin (PG) E2 synthesis increased HSC numbers, and those that block prostaglandin synthesis decreased stem cell numbers. The cyclooxygenases responsible for PGE2 synthesis were required for HSC formation. A stable derivative of PGE2 improved kidney marrow recovery following irradiation injury in the adult zebrafish. In murine embryonic stem cell differentiation assays, PGE2 caused amplification of multipotent progenitors. Furthermore, ex vivo exposure to stabilized PGE2 enhanced spleen colony forming units at day 12 post transplant and increased the frequency of long-term repopulating HSCs present in murine bone marrow after limiting dilution competitive transplantation. The conserved role for PGE2 in the regulation of vertebrate HSC homeostasis indicates that modulation of the prostaglandin pathway may facilitate expansion of HSC number for therapeutic purposes. PMID:17581586

  20. The use of stem cells to study autism spectrum disorder.

    PubMed

    Ardhanareeswaran, Karthikeyan; Coppola, Gianfilippo; Vaccarino, Flora

    2015-03-01

    Autism spectrum disorder (ASD) affects as many as 1 in 68 children and is said to be the fastest-growing serious developmental disability in the United States. There is currently no medical cure or diagnostic test for ASD. Furthermore, the U.S. Food and Drug Administration has yet to approve a single drug for the treatment of autism's core symptoms. Despite numerous genome studies and the identification of hundreds of genes that may cause or predispose children to ASD, the pathways underlying the pathogenesis of idiopathic ASD still remain elusive. Post-mortem brain samples, apart from being difficult to obtain, offer little insight into a disorder that arises through the course of development. Furthermore, ASD is a disorder of highly complex, human-specific behaviors, making it difficult to model in animals. Stem cell models of ASD can be generated by performing skin biopsies of ASD patients and then dedifferentiating these fibroblasts into human-induced pluripotent stem cells (hiPSCs). iPSCs closely resemble embryonic stem cells and retain the unique genetic signature of the ASD patient from whom they were originally derived. Differentiation of these iPSCs into neurons essentially recapitulates the ASD patient's neuronal development in a dish, allowing for a patient-specific model of ASD. Here we review our current understanding of the underlying neurobiology of ASD and how the use of stem cells can advance this understanding, possibly leading to new therapeutic avenues.

  1. Recent Stem Cell Advances: Cord Blood and Induced Pluripotent Stem Cell for Cardiac Regeneration- a Review

    PubMed Central

    Medhekar, Sheetal Kashinath; Shende, Vikas Suresh; Chincholkar, Anjali Baburao

    2016-01-01

    Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field. PMID:27426082

  2. Recent Stem Cell Advances: Cord Blood and Induced Pluripotent Stem Cell for Cardiac Regeneration- a Review.

    PubMed

    Medhekar, Sheetal Kashinath; Shende, Vikas Suresh; Chincholkar, Anjali Baburao

    2016-05-30

    Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue. Day by day increase in incidence of heart diseases including left ventricular dysfunction, ischemic heart disease (IHD), congestive heart failure (CHF) are the major cause of morbidity and mortality. However infracted tissue cannot regenerate into healthy tissue. Heart transplantation is only the treatment for such patient. Due to limitation of availability of donor for organ transplantation, a focus is made for alternative and effective therapy to treat such condition. In this review we have discussed the new advances in stem cells such as use of cord stem cells and iPSC technology in cardiac repair. Future approach of CB cells was found to be used in tissue repair which is specifically observed for improvement of left ventricular function and myocardial infarction. Here we have also focused on how iPSC technology is used for regeneration of cardiomyocytes and intiating neovascularization in myocardial infarction and also for study of pathophysiology of various degenerative diseases and genetic disease in research field.

  3. The CCR4-NOT complex mediates deadenylation and degradation of stem cell mRNAs and promotes planarian stem cell differentiation.

    PubMed

    Solana, Jordi; Gamberi, Chiara; Mihaylova, Yuliana; Grosswendt, Stefanie; Chen, Chen; Lasko, Paul; Rajewsky, Nikolaus; Aboobaker, A Aziz

    2013-01-01

    Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A) tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A) tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology.

  4. The CCR4-NOT Complex Mediates Deadenylation and Degradation of Stem Cell mRNAs and Promotes Planarian Stem Cell Differentiation

    PubMed Central

    Solana, Jordi; Gamberi, Chiara; Mihaylova, Yuliana; Grosswendt, Stefanie; Chen, Chen; Lasko, Paul; Rajewsky, Nikolaus; Aboobaker, A. Aziz

    2013-01-01

    Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A) tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A) tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology. PMID:24367277

  5. Inflammation Shapes Stem Cells and Stemness during Infection and Beyond

    PubMed Central

    Michael, Stella; Achilleos, Charis; Panayiotou, Theofano; Strati, Katerina

    2016-01-01

    The outcome of an inflammatory incident can hang in the balance between restoring health and tissue integrity on the one hand, and promoting aberrant tissue homeostasis and adverse outcomes on the other. Both microbial-related and sterile inflammation is a complex response characterized by a range of innate immune cell types, which produce and respond to cytokine mediators and other inflammatory signals. In turn, cells native to the tissue in question can sense these mediators and respond by migrating, proliferating and regenerating the tissue. In this review we will discuss how the specific outcomes of inflammatory incidents are affected by the direct regulation of stem cells and cellular plasticity. While less well appreciated than the effects of inflammatory signals on immune cells and other differentiated cells, the effects are crucial in understanding inflammation and appropriately managing therapeutic interventions. PMID:27853732

  6. Stem Cell Therapies in Retinal Disorders

    PubMed Central

    Garg, Aakriti; Yang, Jin; Lee, Winston; Tsang, Stephen H.

    2017-01-01

    Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable. PMID:28157165

  7. Large animal models for stem cell therapy.

    PubMed

    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-03-28

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  8. Optimizing stem cells for cardiac repair: Current status and new frontiers in regenerative cardiology

    PubMed Central

    Der Sarkissian, Shant; Lévesque, Thierry; Noiseux, Nicolas

    2017-01-01

    Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the post-ischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring

  9. Optimizing stem cells for cardiac repair: Current status and new frontiers in regenerative cardiology.

    PubMed

    Der Sarkissian, Shant; Lévesque, Thierry; Noiseux, Nicolas

    2017-01-26

    Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the post-ischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring

  10. The therapeutic potential of embryonic stem cells: A focus on stem cell stability.

    PubMed

    Zeng, Xianmin; Rao, Mahendra S

    2006-08-01

    Most therapeutic uses of stem cells demand that large numbers of cells are maintained in a Good Manufacturing Practice (GMP) facility, and envisage the development of a master depository from which a working bank of cells can be retrieved and differentiated into an appropriate phenotype for use. Likewise for gene- and drug-discovery processes, it is assumed that stable and genetically identical cells will eventually become available in large numbers. Critical for both of these assumptions is that the stem cells are stable during periods of amplification and differentiation. This review discusses the physiological features that must be assessed to measure stem cell stability, and proposes that genomic, epigenomic and mitochondrial markers, as well as functional measures of utility, should be considered. Recent findings suggesting that the level of cell stability is not homogeneous throughout all stem cells are also discussed.

  11. Adult stem cells underlying lung regeneration.

    PubMed

    Xian, Wa; McKeon, Frank

    2012-03-01

    Despite the massive toll in human suffering imparted by degenerative lung disease, including COPD, idiopathic pulmonary fibrosis and ARDS, the scientific community has been surprisingly agnostic regarding the potential of lung tissue, and in particular the alveoli, to regenerate. However, there is circumstantial evidence in humans and direct evidence in mice that ARDS triggers robust regeneration of lung tissue rather than irreversible fibrosis. The stem cells responsible for this remarkable regenerative process has garnered tremendous attention, most recently yielding a defined set of cloned human airway stem cells marked by p63 expression but with distinct commitment to differentiated cell types typical of the upper or lower airways, the latter of which include alveoli-like structures in vitro and in vivo. These recent advances in lung regeneration and distal airway stem cells and the potential of associated soluble factors in regeneration must be harnessed for therapeutic options in chronic lung disease.

  12. Stem cell therapy: facts and fiction.

    PubMed

    Spits, C

    2012-01-01

    This opinion paper is a brief overview of the current state of the translation of stem cell therapy from the bench to the clinic. The hype generated by the great medical potential of stem cells has lead to hundreds of clinics worldwide claiming to have the cure for every imaginable condition. This fraudulent practice is far from the reality of scientists and bona fide companies. Much effort is put into addressing all the hurdles we have been encountering for the safe use of stem cells in therapy. By now, a significant number of clinical trials are booking very exciting progress, opening a realistic path to the use of these amazing cells in regenerative medicine.

  13. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    PubMed Central

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM’s cancer biology. PMID:27148537

  14. Colon cancer stem cells: controversies and perspectives.

    PubMed

    Puglisi, Maria Ausiliatrice; Tesori, Valentina; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-05-28

    Tumors have long been viewed as a population in which all cells have the equal propensity to form new tumors, the so called conventional stochastic model. The cutting-edge theory on tumor origin and progression, tends to consider cancer as a stem cell disease. Stem cells are actively involved in the onset and maintenance of colon cancer. This review is intended to examine the state of the art on colon cancer stem cells (CSCs), with regard to the recent achievements of basic research and to the corresponding translational consequences. Specific prominence is given to the hypothesized origin of CSCs and to the methods for their identification. The growing understanding of CSC biology is driving the optimization of novel anti-cancer targeted drugs.

  15. Hematopoietic stem cell origin of connective tissues.

    PubMed

    Ogawa, Makio; Larue, Amanda C; Watson, Patricia M; Watson, Dennis K

    2010-07-01

    Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications.

  16. Stem cell therapy for diabetes mellitus

    PubMed Central

    Voltarelli, Júlio C; Couri, Carlos E B; Oliveira, Maria C; Moraes, Daniela A; Stracieri, Ana B P L; Pieroni, Fabiano; Barros, George M N; Malmegrim, Kelen C R; Simões, Belinda P; Leal, Angela M O; Foss, Milton C

    2011-01-01

    In this review, we present (1) a brief discussion of hematopoietic stem cell transplantation (HSCT) for severe and refractory autoimmune diseases (AIDs) from its beginning in 1996 through recently initiated prospective randomized clinical trials; (2) an update (up to July 2009) of clinical and laboratory outcomes of 23 patients with newly diagnosed type 1 diabetes mellitus (T1DM), who underwent autologous HSCT at the Bone Marrow Transplantation Unit of the Ribeirão Preto Medical School, University of São Paulo, Brazil; (3) a discussion of possible mechanisms of action of HSCT in AIDs, including preliminary laboratory data obtained from our patients; and (4) a discussion of future perspectives of stem cell therapy for T1DM and type 2 DM, including the use of stem cell sources other than adult bone marrow and the combination of cell therapy with regenerative compounds. PMID:25018908

  17. [Stem cell perspectives in myocardial infarctions].

    PubMed

    Aceves, José Luis; Archundia, Abel; Díaz, Guillermo; Páez, Araceli; Masso, Felipe; Alvarado, Martha; López, Manuel; Aceves, Rocío; Ixcamparij, Carlos; Puente, Adriana; Vilchis, Rafael; Montaño, Luis Felipe

    2005-01-01

    Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.

  18. Biodegradable Polymers and Stem Cells for Bioprinting.

    PubMed

    Lei, Meijuan; Wang, Xiaohong

    2016-04-29

    It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism.

  19. Substrates for clinical applicability of stem cells

    PubMed Central

    Enam, Sanjar; Jin, Sha

    2015-01-01

    The capability of human pluripotent stem cells (hPSCs) to differentiate into a variety of cells in the human body holds great promise for regenerative medicine. Many substrates exist on which hPSCs can be self-renewed, maintained and expanded to further the goal of clinical application of stem cells. In this review, we highlight numerous extracellular matrix proteins, peptide and polymer based substrates, scaffolds and hydrogels that have been pioneered. We discuss their benefits and shortcomings and offer future directions as well as emphasize commercially available synthetic peptides as a type of substrate that can bring the benefits of regenerative medicine to clinical settings. PMID:25815112

  20. Metabolic Reprogramming of Stem Cell Epigenetics

    PubMed Central

    Ryall, James G.; Cliff, Tim; Dalton, Stephen; Sartorelli, Vittorio

    2015-01-01

    Summary For many years, stem cell metabolism was viewed as a by product of cell fate status rather than an active regulatory mechanism, however there is now a growing appreciation that metabolic pathways influence epigenetic changes associated with lineage commitment, specification, and self-renewal. Here we review how metabolites generated during glycolytic and oxidative processes are utilized in enzymatic reactions leading to epigenetic modifications and transcriptional regulation. We discuss how “metabolic reprogramming” contributes to global epigenetic changes in the context of naïve and primed pluripotent states, somatic reprogramming, and hematopoietic and skeletal muscle tissue stem cells, and the implications for regenerative medicine. PMID:26637942

  1. The ethics of stem cells revisited.

    PubMed

    de Miguel-Beriain, Iñigo

    2015-03-01

    Stem cells constitute one of the most promising tools for regenerative medicine. Thus, it seems morally compelling to explore all the sources that might provide us with them. However, some of these sources, such as somatic cell nuclear transfer, embryo destruction, or even induced pluripotency obtained by reprogramming have raised deep ethical issues. The aim of this paper is to reflect on the stem cell ethical debate at the current moment through an analysis of the academic literature. It will also provide an analysis of the ethical implications of the most relevant scientific advances that have happened in recent months or those which seem about to merge.

  2. Rethinking differentiation: Stem cells, regeneration, and plasticity

    PubMed Central

    Alvarado, Alejandro Sánchez; Yamanaka, Shinya

    2014-01-01

    Cell differentiation is an essential process for the development, growth, reproduction and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past 4 decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and animals, as well as novel experimental manipulations are beginning to erode many of these established concepts, and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process. PMID:24679530

  3. Regenerating new heart with stem cells

    PubMed Central

    Anversa, Piero; Kajstura, Jan; Rota, Marcello; Leri, Annarosa

    2013-01-01

    This article discusses current understanding of myocardial biology, emphasizing the regeneration potential of the adult human heart and the mechanisms involved. In the last decade, a novel conceptual view has emerged. The heart is no longer considered a postmitotic organ, but is viewed as a self-renewing organ characterized by a resident stem cell compartment responsible for tissue homeostasis and cardiac repair following injury. Additionally, HSCs possess the ability to transdifferentiate and acquire the cardiomyocyte, vascular endothelial, and smooth muscle cell lineages. Both cardiac and hematopoietic stem cells may be used therapeutically in an attempt to reverse the devastating consequences of chronic heart failure of ischemic and nonischemic origin. PMID:23281411

  4. What's missing? Discussing stem cell translational research in educational information on stem cell "tourism".

    PubMed

    Master, Zubin; Zarzeczny, Amy; Rachul, Christen; Caulfield, Timothy

    2013-01-01

    Stem cell tourism is a growing industry in which patients pursue unproven stem cell therapies for a wide variety of illnesses and conditions. It is a challenging market to regulate due to a number of factors including its international, online, direct-to-consumer approach. Calls to provide education and information to patients, their families, physicians, and the general public about the risks associated with stem cell tourism are mounting. Initial studies examining the perceptions of patients who have pursued stem cell tourism indicate many are highly critical of the research and regulatory systems in their home countries and believe them to be stagnant and unresponsive to patient needs. We suggest that educational material should include an explanation of the translational research process, in addition to other aspects of stem cell tourism, as one means to help promote greater understanding and, ideally, curb patient demand for unproven stem cell interventions. The material provided must stress that strong scientific research is required in order for therapies to be safe and have a greater chance at being effective. Through an analysis of educational material on stem cell tourism and translational stem cell research from patient groups and scientific societies, we describe essential elements that should be conveyed in educational material provided to patients. Although we support the broad dissemination of educational material on stem cell translational research, we also acknowledge that education may simply not be enough to engender patient and public trust in domestic research and regulatory systems. However, promoting patient autonomy by providing good quality information to patients so they can make better informed decisions is valuable in itself, irrespective of whether it serves as an effective deterrent of stem cell tourism.

  5. MicroRNA reins in embryonic and cancer stem cells.

    PubMed

    Mallick, Bibekanand; Chakrabarti, Jayprokas; Ghosh, Zhumur

    2011-01-01

    MicroRNAs represents a new layer of gene regulation in stem cells by controlling the molecular mechanisms involved in modulating stem cell fate and behavior. Such a role of microRNA is seen in embryonic stem cell as well, maintaining a delicate balance between survival, proliferation, and self-renewal signals. Further, dysregulation of stem cell self-renewal is a likely requirement for the initiation and formation of cancer stem cells that probably pose resistance to current cancer treatments. In fact, the precise mechanism that regulates embryonic as well as cancer stem cell self-renewal and pluripotency remains largely unknown. Understanding the miRNA related stem cell biology and pathways offers great promise for improving stem cell mediated regenerative therapy as well as cancer therapies. Here we summarize some of the emerging evidences demonstrating the role of these molecular switches in embryonic and cancer stem cells.

  6. Engineering Replacement Tissues with Amniotic Stem Cells

    DTIC Science & Technology

    2012-10-01

    stromal cells. Stem Cells, 2007. 25(3): p. 655-63. 12. Ivan, M., et al., HIFalpha targeted for VHL -mediated destruction by proline hydroxylation...11. Ivan, M., et al., HIFalpha targeted for VHL -mediated destruction by proline hydroxylation: implications for O2 sensing. Science, 2001. 292(5516

  7. Potentiality of embryonic stem cells: an ethical problem even with alternative stem cell sources.

    PubMed

    Denker, H-W

    2006-11-01

    The recent discussions about alternative sources of human embryonic stem cells (White Paper of the US President's Council on Bioethics, 2005), while stirring new interest in the developmental potential of the various abnormal embryos or constructs proposed as such sources, also raise questions about the potential of the derived embryonic stem cells. The data on the developmental potential of embryonic stem cells that seem relevant for ethical considerations and aspects of patentability are discussed. Particular attention is paid to the meaning of "totipotency, omnipotency and pluripotency" as illustrated by a comparison of the developmental potential of three-dimensional clusters of blastomeres (morula), embryonic stem cells, somatic or (adult) stem cells or other somatic (non-stem) cells. This paper focuses on embryoid bodies and on direct cloning by tetraploid complementation. Usage and patenting of these cells cannot be considered to be ethically sound as long as totipotency and tetraploid complementability of embryonic stem cells are not excluded for the specific cell line in question. Testing this poses an ethical problem in itself and needs to be discussed in the future.

  8. The promises of stem cells: stem cell therapy for movement disorders.

    PubMed

    Mochizuki, Hideki; Choong, Chi-Jing; Yasuda, Toru

    2014-01-01

    Despite the multitude of intensive research, the exact pathophysiological mechanisms underlying movement disorders including Parkinson's disease, multiple system atrophy and Huntington's disease remain more or less elusive. Treatments to halt these disease progressions are currently unavailable. With the recent induced pluripotent stem cells breakthrough and accomplishment, stem cell research, as the vast majority of scientists agree, holds great promise for relieving and treating debilitating movement disorders. As stem cells are the precursors of all cells in the human body, an understanding of the molecular mechanisms that govern how they develop and work would provide us many fundamental insights into human biology of health and disease. Moreover, stem-cell-derived neurons may be a renewable source of replacement cells for damaged neurons in movement disorders. While stem cells show potential for regenerative medicine, their use as tools for research and drug testing is thought to have more immediate impact. The use of stem-cell-based drug screening technology could be a big boost in drug discovery for these movement disorders. Particular attention should also be given to the involvement of neural stem cells in adult neurogenesis so as to encourage its development as a therapeutic option.

  9. Neural stem cell progeny regulate stem cell death in a Notch and Hox dependent manner

    PubMed Central

    Arya, R; Sarkissian, T; Tan, Y; White, K

    2015-01-01

    Cell death is a prevalent, well-controlled and fundamental aspect of development, particularly in the nervous system. In Drosophila, specific neural stem cells are eliminated by apoptosis during embryogenesis. In the absence of apoptosis, these stem cells continue to divide, resulting in a dramatically hyperplastic central nervous system and adult lethality. Although core cell death pathways have been well described, the spatial, temporal and cell identity cues that activate the cell death machinery in specific cells are largely unknown. We identified a cis-regulatory region that controls the transcription of the cell death activators reaper, grim and sickle exclusively in neural stem cells. Using a reporter generated from this regulatory region, we found that Notch activity is required for neural stem cell death. Notch regulates the expression of the abdominalA homeobox protein, which provides important spatial cues for death. Importantly, we show that pro-apoptotic Notch signaling is activated by the Delta ligand expressed on the neighboring progeny of the stem cell. Thus we identify a previously undescribed role for progeny in regulating the proper developmental death of their parental stem cells. PMID:25633198

  10. Stem cell sources for cardiac regeneration.

    PubMed

    Roccio, M; Goumans, M J; Sluijter, J P G; Doevendans, P A

    2008-03-01

    Cell-based cardiac repair has the ambitious aim to replace the malfunctioning cardiac muscle developed after myocardial infarction, with new contractile cardiomyocytes and vessels. Different stem cell populations have been intensively studied in the last decade as a potential source of new cardiomyocytes to ameliorate the injured myocardium, compensate for the loss of ventricular mass and contractility and eventually restore cardiac function. An array of cell types has been explored in this respect, including skeletal muscle, bone marrow derived stem cells, embryonic stem cells (ESC) and more recently cardiac progenitor cells. The best-studied cell types are mouse and human ESC cells, which have undisputedly been demonstrated to differentiate into cardiomyocyte and vascular lineages and have been of great help to understand the differentiation process of pluripotent cells. However, due to their immunogenicity, risk of tumor development and the ethical challenge arising from their embryonic origin, they do not provide a suitable cell source for a regenerative therapy approach. A better option, overcoming ethical and allogenicity problems, seems to be provided by bone marrow derived cells and by the recently identified cardiac precursors. This report will overview current knowledge on these different cell types and their application in cardiac regeneration and address issues like implementation of delivery methods, including tissue engineering approaches that need to be developed alongside.

  11. Stem cells and the developing mammary gland.

    PubMed

    Makarem, Maisam; Spike, Benjamin T; Dravis, Christopher; Kannan, Nagarajan; Wahl, Geoffrey M; Eaves, Connie J

    2013-06-01

    The mammary gland undergoes dynamic changes throughout life. In the mouse, these begin with initial morphogenesis of the gland in the mid-gestation embryo followed by hormonally regulated changes during puberty and later in adulthood. The adult mammary gland contains a hierarchy of cell types with varying potentials for self-maintenance and differentiation. These include cells able to produce complete, functional mammary glands in vivo and that contain daughter cells with the same remarkable regenerative potential, as well as cells with more limited clonogenic activity in vitro. Here we review how applying in vitro and in vivo methods for quantifying these cells in adult mammary tissue to fetal mammary cells has enabled the first cells fulfilling the functional criteria of transplantable, isolated mammary stem cells to be identified a few days before birth. Thereafter, the number of these cells increases rapidly. Populations containing these fetal stem cells display growth and gene expression programs that differ from their adult counterparts but share signatures characteristic of certain types of breast cancer. Such observations reinforce growing evidence of important differences between tissue-specific fetal and adult cells with stem cell properties and emphasize the merits of investigating their molecular basis.

  12. Human embryonic stem cells and respect for life

    PubMed Central

    Meyer, J.

    2000-01-01

    The purpose of this essay is to stimulate academic discussion about the ethical justification of using human primordial stem cells for tissue transplantation, cell replacement, and gene therapy. There are intriguing alternatives to using embryos obtained from elective abortions and in vitro fertilisation to reconstitute damaged or dysfunctional human organs. These include the expansion and transplantation of latent adult progenitor cells. Key Words: Primordial stem cell research • embryonic stem cells • pluripotent stem cells • embryo research PMID:10860206

  13. Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming hypothesis of cancer?

    PubMed

    Trosko, James E

    2014-01-01

    This article as designed to examine whether the "stoichiometric" or "elite models" of the origin of the "induced pluripotent stem" (iPS) cells fits some experiment facts from the developmental biology of adult stem cells and from the field of cancer research. In brief, since the evidence presented to support the stoichiometric model failed to recognize the factual existence of adult organ specific stem cells, the model has not been rigorously tested. In addition, the demonstration of a subset of cells (MUSE cells) in normal primary in vitro cultures of human fibroblasts (the usual source of iPS cells) seems to be the origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem cell" versus "de-differentiation" or "reprogramming" hypotheses were examined. Again, using the role of glycolysis, known to be associated with the Warburg effect in cancer cells, a list of experiments showing that (a) normal stem cells, which have few mitochondria, metabolize via glycolysis; (b) the stem cells are targets for "initiation" or "immortalization" or the blockage of differentiation and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate dehydrogenase A (LDHA), when expressed, is associated with glycolysis and therefore, must be expressed in normal adult stem cells, as well as in cancer cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen, is associated with the reduction of mitochondrial function and mass and is associated with the Warburg effect. Together, these observations from the iPS and "cancer stem cell" fields support the idea that both iPS cells and cancer stem cell are derived from adult organ-specific stem cells that do not restore or switch their metabolism of glucose from oxidative metabolism to glycolysis but, rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is prevented from differentiation or from metabolizing by oxidative phosphorylation.

  14. Cancer stem cells in nervous system tumors.

    PubMed

    Singh, Sheila K; Clarke, Ian D; Hide, Takuichiro; Dirks, Peter B

    2004-09-20

    Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and more recently in solid tumors such as breast cancer suggests that the tumor cell population is heterogeneous with respect to proliferation and differentiation. Recently, several groups have described the existence of a cancer stem cell population in human brain tumors of different phenotypes from both children and adults. The finding of brain tumor stem cells (BTSCs) has been made by applying the principles for cell culture and analysis of normal neural stem cells (NSCs) to brain tumor cell populations and by identification of cell surface markers that allow for isolation of distinct tumor cell populations that can then be studied in vitro and in vivo. A population of brain tumor cells can be enriched for BTSCs by cell sorting of dissociated suspensions of tumor cells for the NSC marker CD133. These CD133+ cells, which also expressed the NSC marker nestin, but not differentiated neural lineage markers, represent a minority fraction of the entire brain tumor cell population, and exclusively generate clonal tumor spheres in suspension culture and exhibit increased self-renewal capacity. BTSCs can be induced to differentiate in vitro into tumor cells that phenotypically resembled the tumor from the patient. Here, we discuss the evidence for and implications of the discovery of a cancer stem cell in human brain tumors. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC. Specific genetic and molecular analyses of the BTSC will further our understanding of the mechanisms of brain tumor growth, reinforcing parallels between normal neurogenesis and brain tumorigenesis.

  15. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    PubMed

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  16. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    PubMed Central

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  17. Post-transplant adoptive T-cell immunotherapy

    PubMed Central

    Aqui, Nicole A.; June, Carl H.

    2008-01-01

    Immune reconstitution following haematopoietic stem cell transplantation (SCT) is an often slow and incomplete process that leads to increased risk of infection and malignant disease. Immunization in SCT is frequently unsuccessful due to the prolonged lymphopenia, especially of CD4 T cells, seen following transplant. The transfusion of T cells, also called ‘adoptive T-cell therapy’, has the potential to enhance anti-tumour and overall immunity, and augment vaccine efficacy in the post-transplant setting. Recent advances in tissue culture, cellular immunology and tumour biology are guiding new approaches to adoptive T-cell therapy. This chapter will discuss the challenges that face the field before adoptive T-cell therapy can be translated into routine clinical practice. PMID:18790452

  18. The Emerging Cell Biology of Thyroid Stem Cells

    PubMed Central

    Latif, Rauf; Minsky, Noga C.; Ma, Risheng

    2011-01-01

    Context: Stem cells are undifferentiated cells with the property of self-renewal and give rise to highly specialized cells under appropriate local conditions. The use of stem cells in regenerative medicine holds great promise for the treatment of many diseases, including those of the thyroid gland. Evidence Acquisition: This review focuses on the progress that has been made in thyroid stem cell research including an overview of cellular and molecular events (most of which were drawn from the period 1990–2011) and discusses the remaining problems encountered in their differentiation. Evidence Synthesis: Protocols for the in vitro differentiation of embryonic stem cells, based on normal developmental processes, have generated thyroid-like cells but without full thyrocyte function. However, agents have been identified, including activin A, insulin, and IGF-I, which are able to stimulate the generation of thyroid-like cells in vitro. In addition, thyroid stem/progenitor cells have been identified within the normal thyroid gland and within thyroid cancers. Conclusions: Advances in thyroid stem cell biology are providing not only insight into thyroid development but may offer therapeutic potential in thyroid cancer and future thyroid cell replacement therapy. PMID:21778219

  19. Induced pluripotent stem cells for regenerative medicine.

    PubMed

    Hirschi, Karen K; Li, Song; Roy, Krishnendu

    2014-07-11

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.

  20. Metaboloepigenetic Regulation of Pluripotent Stem Cells

    PubMed Central

    Harvey, Alexandra J.; Gardner, David K.

    2016-01-01

    The differentiation of pluripotent stem cells is associated with extensive changes in metabolism, as well as widespread remodeling of the epigenetic landscape. Epigenetic regulation is essential for the modulation of differentiation, being responsible for cell type specific gene expression patterns through the modification of DNA and histones, thereby establishing cell identity. Each cell type has its own idiosyncratic pattern regarding the use of specific metabolic pathways. Rather than simply being perceived as a means of generating ATP and building blocks for cell growth and division, cellular metabolism can directly influence cellular regulation and the epigenome. Consequently, the significance of nutrients and metabolites as regulators of differentiation is central to understanding how cells interact with their immediate environment. This review serves to integrate studies on pluripotent stem cell metabolism, and the regulation of DNA methylation and acetylation and identifies areas in which current knowledge is limited. PMID:26839556

  1. Biomaterial Strategies for Stem Cell Maintenance During In Vitro Expansion

    PubMed Central

    Yan, Xiang-Zhen; van den Beucken, Jeroen J.J.P.; Both, Sanne K.; Yang, Pi-Shan; Jansen, John A.

    2014-01-01

    Stem cells, having the potential for self-renewal and multilineage differentiation, are the building blocks for tissue/organ regeneration. Stem cells can be isolated from various sources but are, in general, available in too small numbers to be used directly for clinical purpose without intermediate expansion procedures in vitro. Although this in vitro expansion of undifferentiated stem cells is necessary, stem cells typically diminish their ability to self-renew and proliferate during passaging. Consequently, maintaining the stemness of stem cells has been recognized as a major challenge in stem cell-based research. This review focuses on the latest developments in maintaining the self-renewal ability of stem cells during in vitro expansion by biomaterial strategies. Further, this review highlights what should be the focus for future studies using stem cells for regenerative applications. PMID:24168361

  2. Craniofacial Tissue Engineering by Stem Cells

    PubMed Central

    Mao, J.J.; Giannobile, W.V.; Helms, J.A.; Hollister, S.J.; Krebsbach, P.H.; Longaker, M.T.; Shi, S.

    2008-01-01

    Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures—such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue—have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss. PMID:17062735

  3. The development of germline stem cells in Drosophila.

    PubMed

    Dansereau, David A; Lasko, Paul

    2008-01-01

    Germline stem cells (GSCs) in Drosophila are a valuable model to explore of how adult stem cells are regulated in vivo. Genetic dissection of this system has shown that stem cell fate is determined and maintained by the stem cell's somatic microenvironment or niche. In Drosophila gonads, the stem cell niche -- the cap cell cluster in females and the hub in males -- acts as a signaling center to recruit GSCs from among a small population of undifferentiated primordial germ cells (PGCs). Short-range signals from the niche specify and regulate stem cell fate by maintaining the undifferentiated state of the PGCs next to the niche. Germline cells that do not receive the niche signals because of their location assume the default fate and differentiate. Once GSCs are specified, adherens junctions maintain close association between the stem cells and their niche and help to orient stem cell division so that one daughter is displaced from the niche and differentiates. In females, stem cell fate depends on bone morphogenetic protein (BMP) signals from the cap cells; in males, hub cells express the cytokine-like ligand Unpaired, which activates the Janus kinase-signal transducers and activators of transcription (Jak-Stat) pathway in stem cells. Although the signaling pathways operating between the niche and stem cells are different, there are common general features in both males and females, including the arrangement of cell types, many of the genes used, and the logic of the system that maintains stem cell fate.

  4. Mesenchymal stem cell applications to tendon healing

    PubMed Central

    Chaudhury, Salma

    2012-01-01

    Summary Tendons are often subject to age related degenerative changes that coincide with a diminished regenerative capacity. Torn tendons often heal by forming scar tissue that is structurally weaker than healthy native tendon tissue, predisposing to mechanical failure. There is increasing interest in providing biological stimuli to increase the tendon reparative response. Stem cells in particular are an exciting and promising prospect as they have the potential to provide appropriate cellular signals to encourage neotendon formation during repair rather than scar tissue. Currently, a number of issues need to be investigated further before it can be determined whether stem cells are an effective and safe therapeutic option for encouraging tendon repair. This review explores the in-vitro and invivo evidence assessing the effect of stem cells on tendon healing, as well as the potential clinical applications. PMID:23738300

  5. The ethics of human stem cell research.

    PubMed

    Outka, Gene

    2002-06-01

    The medical and clinical promise of stem cell research is widely heralded, but moral judgments about it collide. This article takes general stock of such judgments and offers one specific resolution. It canvasses a spectrum of value judgments on sources, complicity, adult stem cells, and public and private contexts. It then examines how debates about abortion and stem cell research converge and diverge. Finally, it proposes to extend the principle of "nothing is lost" to current debates. This extension links historical discussions of the ethics of direct killing with unprecedented possibilities that in vitro fertilization procedures yield. A definite normative region to inhabit is located, within a larger range of rival value judgments. The creation of embryos for research purposes only should be resisted, yet research on "excess' embryos is permissible by virtue of an appeal to the "nothing is lost" principle.

  6. Nanotechnology for mesenchymal stem cell therapies.

    PubMed

    Corradetti, Bruna; Ferrari, Mauro

    2016-10-28

    Mesenchymal stem cells (MSC) display great proliferative, differentiative, chemotactic, and immune-modulatory properties required to promote tissue repair. Several clinical trials based on the use of MSC are currently underway for therapeutic purposes. The aim of this article is to examine the current trends and potential impact of nanotechnology in MSC-driven regenerative medicine. Nanoparticle-based approaches are used as powerful carrier systems for the targeted delivery of bioactive molecules to ensure MSC long-term maintenance in vitro and to enhance their regenerative potential. Nanostructured materials have been developed to recapitulate the stem cell niche within a tissue and to instruct MSC toward the creation of regeneration-permissive environment. Finally, the capability of MSC to migrate toward the site of injury/inflammation has allowed for the development of diagnostic imaging systems able to monitor transplanted stem cell bio-distribution, toxicity, and therapeutic effectiveness.

  7. Silencing stem cell factor attenuates stemness and inhibits migration of cancer stem cells derived from Lewis lung carcinoma cells.

    PubMed

    Wang, Li; Wang, JianTao; Li, Zhixi; Liu, YanYang; Jiang, Ming; Li, Yan; Cao, Dan; Zhao, Maoyuan; Wang, Feng; Luo, Feng

    2016-06-01

    Stem cell factor (SCF) plays an important role in tumor growth and metastasis. However, the function of SCF in regulating stemness and migration of cancer stem cells (CSCs) remains largely undefined. Here, we report that non-adhesive culture system can enrich and expand CSCs derived from Lewis lung carcinoma (LLC) cells and that the expression level of SCF in CSCs was higher than those in LLC cells. Silencing SCF via short hairpin (sh) RNA lentivirus transduction attenuated sphere formation and inhibited expressions of stemness genes, ALDH1, Sox2, and Oct4 of CSCs in vitro and in vivo. Moreover, SCF-silenced CSCs inhibited the migration and epithelial-mesenchymal transition, with decreased expression of N-cadherin, Vimentin, and increased expression of E-cadherin in vitro and in vivo. Finally, SCF-short hairpin RNA (shRNA) lentivirus transduction suppressed tumorigenicity of CSCs. Taken together, our findings unraveled an important role of SCF in CSCs derived from LLC cells. SCF might serve as a novel target for lung cancer therapy.

  8. Adult stem cells: hopes and hypes of regenerative medicine.

    PubMed

    Dulak, Józef; Szade, Krzysztof; Szade, Agata; Nowak, Witold; Józkowicz, Alicja

    2015-01-01

    Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) differentiate into cells of all three embryonic lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can develop into multiple specialized cells in a specific tissue. Unipotent cells differentiate only into one cell type, like e.g. satellite cells of skeletal muscle. There are many examples of successful clinical applications of stem cells. Over million patients worldwide have benefited from bone marrow transplantations performed for treatment of leukemias, anemias or immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal stem cells can regenerate the damaged cornea. Pluripotent stem cells, especially the patient-specific iPSC, have a tremendous therapeutic potential, but their clinical application will require overcoming numerous drawbacks. Therefore, the use of adult stem cells, which are multipotent or unipotent, can be at present a more achievable strategy. Noteworthy, some studies ascribed particular adult stem cells as pluripotent. However, despite efforts, the postulated pluripotency of such events like "spore-like cells", "very small embryonic-like stem cells" or "multipotent adult progenitor cells" have not been confirmed in stringent independent studies. Also plasticity of the bone marrow-derived cells which were suggested to differentiate e.g. into cardiomyocytes, has not been positively verified, and their therapeutic effect, if observed, results rather from the paracrine activity. Here we discuss the examples of recent studies on adult stem cells in the light of current understanding of stem cell biology.

  9. Ovarian Stem Cells-the Pros and Cons.

    PubMed

    Evron, Ayelet; Blumenfeld, Zeev

    2013-03-20

    The potential for postnatal de novo oogenesis in mammals and in humans has become very controversial in the fields of reproductive science and biology. Historically, it has been thought that females of most mammalian species lose the ability to produce oocytes at birth. A contemporary understanding of stem cell biology together with novel experimental methods has challenged the model of a prenatal fixed ovarian primordial follicle pool that declines with age. Researchers have suggested replenishment of post-natal oocytes by germ-line stem cells (GSCs). According to this theory, GSCs produce oocytes and primordial follicles throughout the lifetime of the adult female. This review describes recent approaches supporting the revolutionary idea of de novo oogenesis in mammals and humans of reproductive-age and provides counter arguments from opponents of this novel and innovative concept.

  10. [Targeted molecular therapy based on advanced cancer stem cell model].

    PubMed

    Hirao, Atsushi

    2015-08-01

    Improvement of cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TICs). Although it was hypothesized that tumors are organized as hierarchies of tumor cells that are sustained by rare TICs, like normal tissue stem cells, there are several controversies towards such cancer stem cell model, e.g. reversible change of stem cell like population based on epigenetic changes, clonal genetic evolution and problems in xenotransplantation system. Despite complexity in cancer stem cell models, studies in cancer stem cell field have revealed that there are close relationship between cancer malignancy and stem cell properties, called "stemness". Understanding molecular mechanisms for controlling stemness would contribute to establishment of novel diagnostics or therapeutics for cancer.

  11. Towards Personalized Regenerative Cell Therapy: Mesenchymal Stem Cells Derived from Human Induced Pluripotent Stem Cells.

    PubMed

    Lin, Lin; Bolund, Lars; Luo, Yonglun

    2016-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self-renewal and multilineage differentiation, and can be isolated from several adult tissues. However, isolating MSCs from adult tissues for cell therapy is hampered by the invasive procedure, the rarity of the cells and their attenuated proliferation capacity when cultivated and expanded in vitro. Human MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising alternative cell source for MSCs and regenerative medicine. Several groups, including ours, have reported successful derivation of functional iPSC-MSCs and applied these cells in MSC-based therapeutic testing. Still, the current experience and understanding of iPSC-MSCs with respect to production methods, safety and efficacy are primitive. In this review, we highlight the methodological progress in iPSC-MSC research, describing the importance of choosing the right sources of iPSCs, iPSC reprogramming methods, iPSC culture systems, embryoid body intermediates, pathway inhibitors, basal medium, serum, growth factors and culture surface coating. We also highlight some progress in the application of iPSC-MSCs in direct cell therapy, tissue engineering and gene therapy.

  12. Secondary Malignant Neoplasms Following Haematopoietic Stem Cell Transplantation in Childhood

    PubMed Central

    Bomken, Simon; Skinner, Roderick

    2015-01-01

    Improving survival rates in children with malignancy have been achieved at the cost of a high frequency of late adverse effects of treatment, especially in intensively treated patients such as those undergoing haematopoietic stem cell transplantation (HSCT), many of whom suffer the high burden of chronic toxicity. Secondary malignant neoplasms (SMNs) are one of the most devastating late effects, cause much morbidity and are the most frequent cause of late (yet still premature) treatment-related mortality. They occur in up to 7% of HSCT recipients by 20 years post-HSCT, and with no evidence yet of a plateau in incidence with longer follow-up. This review describes the epidemiology, pathogenesis, clinical features and risk factors of the three main categories of post-HSCT SMNs. A wide range of solid SMNs has been described, usually occurring 10 years or more post-HSCT, related most often to previous or conditioning radiotherapy. Therapy-related acute myeloid leukaemia/myelodysplasia occurs earlier, typically three to seven years post-HSCT, mainly in recipients of autologous transplant and is related to previous alkylating agent or topoisomerase II inhibitor chemotherapy. Post-transplant lymphoproliferative disorders occur early (usually within two years) post-HSCT, usually presenting as Epstein-Barr virus-related B cell non-Hodgkin lymphoma. PMID:27417356

  13. Induced pluripotent stem cells in cartilage repair

    PubMed Central

    Lietman, Steven A

    2016-01-01

    Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID:27004161

  14. Proteomic Definitions of Mesenchymal Stem Cells

    PubMed Central

    Maurer, Martin H.

    2011-01-01

    Mesenchymal stem cells (MSCs) are pluripotent cells isolated from the bone marrow and various other organs. They are able to proliferate and self-renew, as well as to give rise to progeny of at least the osteogenic, chondrogenic, and adipogenic lineages. Despite this functional definition, MSCs can also be defined by their expression of a distinct set of cell surface markers. In the current paper, studies investigating the proteome of human MSCs are reviewed with the aim to identify common protein markers of MSCs. The proteomic analysis of MSCs revealed a distinct set of proteins representing the basic molecular inventory, including proteins for (i) cell surface markers, (ii) the responsiveness to growth factors, (iii) the reuse of developmental signaling cascades in adult stem cells, (iv) the interaction with molecules of the extracellular matrix, (v) the expression of genes regulating transcription and translation, (vi) the control of the cell number, and (vii) the protection against cellular stress. PMID:21437194

  15. Stem cell therapy for treatment of epilepsy.

    PubMed

    Goodarzi, Parisa; Aghayan, Hamid Reza; Soleimani, Masoud; Norouzi-Javidan, Abbas; Mohamadi-Jahani, Fereshteh; Jahangiri, Sharareh; Emami-Razavi, Seyed Hasan; Larijani, Bagher; Arjmand, Babak

    2014-01-01

    Epilepsy as one of the most common neurological disorders affects more than 50 million people worldwide with a higher prevalence rate in low-income countries. Excessive electrical discharges in neurons following neural cell damage or loss cause recurrent seizures. One of the most common and difficult to treat types of epilepsy is temporal lobe epilepsy (TLE) which results from hippocampal sclerosis. Nowadays, similar to other diseases, epilepsy also is a candidate for treatment with different types of stem cells. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. Two major roles of stem cell therapy in epilepsy are prophylaxis against chronic epilepsy and amelioration cognitive function after the occurrence of TLE. Several animal studies have supported the use of these cells for treating drug-resistant TLE. Although stem cell therapy seems like a promising approach for treatment of epilepsy in the future however, there are some serious safety and ethical concerns that are needed to be eliminated before clinical application.

  16. Redox Regulation in Cancer Stem Cells

    PubMed Central

    Ding, Shijie; Li, Chunbao; Cheng, Ninghui; Cui, Xiaojiang; Xu, Xinglian; Zhou, Guanghong

    2015-01-01

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs) has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortun