Sample records for stem cells effect

  1. 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 ...

  2. Mechanisms of stem cell effects: insights from MRI.

    PubMed

    Rokosh, G; Ghafghazi, S; Bolli, R

    2013-12-01

    Early results from stem cell trials to treat myocardial infarction have shown promise. Several types of stem cells have moved through phase I trials to demonstrate safety and some at the same time have shown significant potential for myocardial regeneration and functional recovery. The means by which stem cells contribute to improving myocardial function, however, remains unknown. Challenges in labeling stem cells for tracking and fate determination after cell transplantation have precluded establishing whether transplanted stem cell engraftment, expansion after engraftment, endogenous stem cell activation or a combination of these mechanisms contribute to improved function. Cardiac magnetic resonance imaging (cMRI), due to its inherent capabilities, has emerged as the imaging modality of choice to provide important insights into remodeling of myocardium after stem cell transplantation and its consequences on cardiac function. Of cMRI capabilities, excellent spatial resolution is instrumental in assessment of global and regional function and feasibility of scar quantification sets it apart from other imaging modalities and facilitates critical analysis. These capabilities permit the identification of dysfunctional myocardium and scar and changes in these regions over time. The effect of stem cell therapeutics on dysfunctional myocardium and scar can then be highlighted in longitudinal assessment in clinical trials. This has been demonstrated in the inaugural Phase I SCIPIO trial where patients received autologous C-kitPos cardiac stem cell (CSC) transplantation. Although the global function improved significantly with CSC transplantation, regional/segmental analysis provided crucial insights into the effects of CSCs on the most dysfunctional myocardial segments. Magnetic resonance imaging is also a contending and complementing modality in molecular imaging essential for mechanistic studies. PMID:24253454

  3. Immunomodulatory Effect of Mesenchymal Stem Cells on B Cells

    PubMed Central

    Franquesa, Marcella; Hoogduijn, M. J.; Bestard, O.; Grinyó, J. M.

    2012-01-01

    The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches. Mesenchymal stem cells (MSC) are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties. The research on MSCs has mainly focused on their effects on T cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field. PMID:22833744

  4. Mesenchymal stem cell effects on T-cell effector pathways

    Microsoft Academic Search

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

    2011-01-01

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

  5. Stem Cell Basics

    MedlinePLUS

    ... Info Center Stem Cell Basics Stem Cell Basics Stem Cell Information Frequently Asked Questions What are stem cells? ... U.S. policy? More FAQs Links to related resources Stem Cell Research Center for Regenerative Medicine NIH Stem Cell ...

  6. Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

    PubMed Central

    Choi, Moonhwan; Ban, Taehyun; Rhim, Taiyoun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs. PMID:24598998

  7. Effects of engrafted neural stem cells in Alzheimer's disease rats

    Microsoft Academic Search

    A. G. Xuan; M. Luo; W. D. Ji; D. H. Long

    2009-01-01

    Cell therapy is thought to have a central role in restorative therapy, which aims to restore the function of the damaged nervous system. Neural stem cells (NSCs) can differentiate into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the therapeutic effects of transplanting NSCs into rats which have the animal model of Alzheimer's disease (AD). NSCs

  8. Effective Cryopreservation of Human Embryonic Stem Cells By Programmed Freezing

    Microsoft Academic Search

    Peng-Fei Yang; Tse-Chao Hua; Hsiao-Chien Tsung; Qi-Kang Cheng; Yi-Lin Cao

    2005-01-01

    Cryopreservation of human embryonic stem cells is an important and unsolved problem. A computer-controlled programmable cooler is used in the preservation of ES cells. Several effects have been experimentally studied, which include the cooling rate, the seeding temperature , the terminative temperature before the sample is plunged into liquid nitrogen. It is found that the constitution of cryoprotective agents is

  9. Cell Stem Cell Perspective

    E-print Network

    van Oudenaarden, Alexander

    Cell Stem Cell Perspective Identifying the Stem Cell of the Intestinal Crypt: Strategies.clevers@hubrecht.eu http://dx.doi.org/10.1016/j.stem.2012.09.009 Decades ago, two nonoverlapping crypt stem cell populations were proposed: Leblond's Crypt Base Columnar (CBC) cell and Potten's +4 cell. The identification

  10. TISSUE-SPECIFIC STEM CELLS Regenerative Effects of Transplanted Mesenchymal Stem Cells in

    E-print Network

    Miga, Michael I.

    of this article. INTRODUCTION High-energy tibia fractures are threatening injuries with slow healing times Healing FROILA´ N GRANERO-MOLTO´ ,a JARED A. WEIS,a MICHAEL I. MIGA,b BENJAMIN LANDIS,c TIMOTHY J. MYERS healing · CXCR4 · Bone morphogenic protein 2 · Stem cell niche ABSTRACT Mesenchymal stem cells (MSC) have

  11. Cell Stem Cell Perspective

    E-print Network

    Zhang, Yi

    Cell Stem Cell Perspective Genetic and Epigenetic Variations in iPSCs: Potential Causes Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA 5Harvard Stem Cell Institute, WAB-149G, 200.1016/j.stem.2013.07.001 The ability to reprogram somatic cells to induced pluripotent stem cells (i

  12. Radiation-Induced Bystander Effects in Cultured Human Stem Cells

    Microsoft Academic Search

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

    2010-01-01

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

  13. Stem Cells and Diseases

    MedlinePLUS

    ... Center Can Stem Cells Help my Medical Condition? Stem Cell Information Frequently Asked Questions What are stem cells? ... U.S. policy? More FAQs Links to related resources Stem Cell Research Center for Regenerative Medicine NIH Stem Cell ...

  14. Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior

    NASA Astrophysics Data System (ADS)

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

    2005-08-01

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

  15. Inducing Effects of Zhichan Soup on Neuron Stem Cell Differentiation

    Microsoft Academic Search

    Li Wentao; Li Rukui; Wang Yang; Shi Huifen; Lu Yu

    2009-01-01

    This is an experiment to observe the inducing effects of Zhichan Soup on neuron stem cell (NSC) differentiation. NSCs were divided into three groups. The normal group was treated with the normal medium. The herb group was treated with the Zhichan Soup-medicated sera. The control group was treated with the normal rat sera. After the 21-day treatment, TH and DAT

  16. Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?

    PubMed Central

    Markel, Troy A.; Crisostomo, Paul R.; Manukyan, Maiuxi C.; Al-Azzawi, Dalia; Herring, Christine M.; Lahm, Tim; Novotny, Nathan M.; Meldrum, Daniel R.

    2009-01-01

    Background Bone marrow stem cells (BMSCs) may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. However, stem cells from older hosts exhibit decreased function during stress. We therefore hypothesized that: 1) BMSCs derived from neonatal hosts would provide protection to ischemic myocardium; and 2) neonatal stem cells would enhance post-ischemic myocardial recovery above that seen with adult stem cell therapy. Materials and Methods Female adult Sprague-Dawley rat hearts were subjected to an ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 minutes equilibration, 25 minutes ischemia, and 60 minutes reperfusion). BMSCs were harvested from adult and neonatal mice and cultured through several passages under normal conditions (37 C, 5% CO2/air). Immediately prior to ischemia, one million adult or neonatal BMSCs were infused into the coronary circulation. Cardiac functional parameters were continuously recorded. Results Pretreatment with adult BMSCs significantly increased post-ischemic myocardial recovery as noted by improved left ventricular developed pressure, end diastolic pressure, contractility, and rate of relaxation. Neonatal stem cells, however, did not cause any noticeable improvement in myocardial functional parameters following ischemia. Conclusion Neonatal and adult BMSCs are distinctly different in the degree of beneficial tissue protection that they can provide. The data herein suggests that a critical age exists as to when stem cells become fully activated to provide their beneficial protective properties. Defining the genes that initiate these protective properties may allow for genetic amplification of beneficial signals, and the generation of “super stem cells” that provide maximum protection to ischemic tissues. PMID:18805555

  17. Cancer Stem Cells Implications for Development of More Effective Therapies

    Microsoft Academic Search

    Ilia Mantle; Gabriela Dontu; Suling Liu; Max S. Wicha

    Despite advances in the development of cytotoxic chemotherapies, the fact remains that for most common malignancies, metastatic\\u000a disease remains incurable. Recent work has suggested that most, if not all, malignancies are driven by a small subpopulation\\u000a of cells that have stem cell characteristics. These “tumor stem cells” are thought to arise either from normal tissue stem\\u000a cells or from early

  18. Effects of stem cell therapy on dilated cardiomyopathy

    PubMed Central

    Jiao, Rong; Liu, Yuan; Yang, Wen-Jian; Zhu, Xiao-Yan; Li, Jin; Tang, Qi-Zhu

    2014-01-01

    Objectives: To perform a meta-analysis of clinical trials and investigate the effect of stem cell therapy on dilated cardiomyopathy. Methods: A systematic literature search was carried out between May 2012 and July 2013 in PubMed, Medline, Cochrane Library, and Excerpta Medica Database (EMBASE). The study took place in the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China. The weighted mean difference (WMD) was calculated for left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), mortality and heart transplantation, and the 6-minute walk test (6-MWT) distance using the RevMan 5.0 software. Results: Seven trials with 599 participants evaluated the association between the stem cell therapy and control groups. Compared with the control group, stem cell therapy group improved the LVEF (WMD: 3.98%, 95% confidence interval [CI]: 0.55 - 7.41%, p=0.02) and the 6-MWT distance (WMD: 132.12 m, 95% CI: 88.15-176.09 m, p<0.00001), and reduced mortality and heart transplantation (odds ratio [OR]: 0.48, 95% CI: 0.29-0.80, p=0.005). However, the LVEDD showed no significant difference between the 2 groups (WMD: -1.53 mm, 95% CI: -1.15-0.10 mm, p=0.10). Conclusion: This meta-analysis demonstrated that stem cell therapy improves cardiac function and reduces mortality in dilated cardiomyopathy patients, which suggested that stem cell therapy may represent a new therapy option for dilated cardiomyopathy. PMID:25491210

  19. Stress and stem cells

    PubMed Central

    Tower, John

    2013-01-01

    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. PMID:23799624

  20. Divergent effects of supraphysiologic Notch signals on leukemia stem cells and hematopoietic stem cells

    PubMed Central

    Shestova, Olga; Xu, Lanwei; Aster, Jon C.

    2013-01-01

    The leukemia stem cell (LSC) hypothesis proposes that a subset of cells in the bulk leukemia population propagates the leukemia. We tested the LSC hypothesis in a mouse model of Notch-induced T-cell acute lymphoblastic leukemia (T-ALL) in which the tumor cells were largely CD4+CD8+ T cells. LSC activity was enriched but rare in the CD8+CD4?HSAhi immature single-positive T-cell subset. Although our murine T-ALL model relies on transduction of HSCs, we were unable to isolate Notch-activated HSCs to test for LSC activity. Further analysis showed that Notch activation in HSCs caused an initial expansion of hematopoietic and T-cell progenitors and loss of stem cell quiescence, which was followed by progressive loss of long-term HSCs and T-cell production over several weeks. Similar results were obtained in a conditional transgenic model in which Notch activation is induced in HSCs by Cre recombinase. We conclude that although supraphysiologic Notch signaling in HSCs promotes LSC activity in T-cell progenitors, it extinguishes self-renewal of LT-HSCs. These results provide further evidence for therapeutically targeting T-cell progenitors in T-ALL while also underscoring the need to tightly regulate Notch signaling to expand normal HSC populations for clinical applications. PMID:23115273

  1. Divergent effects of supraphysiologic Notch signals on leukemia stem cells and hematopoietic stem cells.

    PubMed

    Chiang, Mark Y; Shestova, Olga; Xu, Lanwei; Aster, Jon C; Pear, Warren S

    2013-02-01

    The leukemia stem cell (LSC) hypothesis proposes that a subset of cells in the bulk leukemia population propagates the leukemia.We tested the LSC hypothesis in a mouse model of Notch-induced T-cell acute lymphoblastic leukemia (T-ALL) in which the tumor cells were largely CD4+ CD8+ T cells. LSC activity was enriched but rare in the CD8+ CD4 HSA(hi) immature single-positive T-cell subset. Although our murine T-ALL model relies on transduction of HSCs, we were unable to isolate Notch-activated HSCs to test for LSC activity. Further analysis showed that Notch activation in HSCs caused an initial expansion of hematopoietic and T-cell progenitors and loss of stem cell quiescence, which was followed by progressive loss of long-term HSCs and T-cell production over several weeks. Similar results were obtained in a conditional transgenic model in which Notch activation is induced in HSCs by Cre recombinase. We conclude that although supraphysiologic Notch signaling in HSCs promotes LSC activity in T-cell progenitors, it extinguishes self-renewal of LT-HSCs. These results provide further evidence for therapeutically targeting T-cell progenitors in T-ALL while also underscoring the need to tightly regulate Notch signaling to expand normal HSC populations for clinical applications. PMID:23115273

  2. Stem Cell Transplants

    MedlinePLUS

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

  3. Target irradiation induced bystander effects between stem-like and non stem-like cancer cells.

    PubMed

    Liu, Yu; Kobayashi, Alisa; Maeda, Takeshi; Fu, Qibin; Oikawa, Masakazu; Yang, Gen; Konishi, Teruaki; Uchihori, Yukio; Hei, Tom K; Wang, Yugang

    2015-03-01

    Tumors are heterogeneous in nature and consist of multiple cell types. Among them, cancer stem-like cells (CSCs) are suggested to be the principal cause of tumor metastasis, resistance and recurrence. Therefore, understanding the behavior of CSCs in direct and indirect irradiations is crucial for clinical radiotherapy. Here, the CSCs and their counterpart non stem-like cancer cells (NSCCs) in human HT1080 fibrosarcoma cell line were sorted and labeled, then the two cell subtypes were mixed together and chosen separately to be irradiated via a proton microbeam. The radiation-induced bystander effect (RIBE) between the CSCs and NSCCs was measured by imaging 53BP1 foci, a widely used indicator for DNA double strand break (DSB). CSCs were found to be less active than NSCCs in both the generation and the response of bystander signals. Moreover, the nitric oxide (NO) scavenger c-PTIO can effectively alleviate the bystander effect in bystander NSCCs but not in bystander CSCs, indicating a difference of the two cell subtypes in NO signal response. To our knowledge, this is the first report shedding light on the RIBE between CSCs and NSCCs, which might contribute to a further understanding of the out-of-field effect in cancer radiotherapy. PMID:25769186

  4. Stem cells, cancer, and cancer stem cells

    Microsoft Academic Search

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

    2001-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Diop, Rokhaya; Li, Song

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

  6. Effect of Neurotrophic Factors on Neuronal Stem Cell Death

    Microsoft Academic Search

    Yunhee Kim Kwon

    2002-01-01

    Neural cell survival is an essential concern in the aging brain and many diseases of the central nervous system. Neural transplantation of the stem cells are already applied to clinical trials for many degenerative neurological diseases, including Huntington's disease, Parkinson's disease, and strokes. A critical problem of the neural transplantation is how to reduce their apoptosis and improve cell survival.

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

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  8. 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.

  9. Effects of Stem Cell Factor on the Growth and Radiation Survival of Tumor Cells1

    Microsoft Academic Search

    Chaoxiang Shui; Waqqar B. Khan; Bryan R. Leigh; Anne M. Turner; Richard B. Wilder; Susan J. Knox

    Recombinant human stem cell factor (SCF) binds to the c-kit receptor on human bone marrow progenitor cells and enhances their survival following irradiation. Since the c-kil receptor has also been detected on malignant cells, experiments were performed to study the effect of SCF on the proliferation and radiation survival of a variety of both c-foY-positive and -negative human tumor cell

  10. Epithelial Cells Stem Cells

    E-print Network

    SchĂĽler, Axel

    Keywords Epithelial Cells Keratins Stem Cells » Prof. Thomas M. Magin Epithelia protect the body, altered cell adhesion and signal- ling. As no molecular therapy for these conditions is available, one that the co-chaperone CHIP can remove mutant aggregated keratins in a cell culture model of EBS, leading

  11. Cell Stem Cell From Stem Cells to Grandmother Cells

    E-print Network

    Shors, Tracey J.

    how learning enhances the survival of neural stem/progenitor cell progeny and what these new neuronsCell Stem Cell Commentary From Stem Cells to Grandmother Cells: How Neurogenesis Relates@rutgers.edu DOI 10.1016/j.stem.2008.08.010 Neurogenesis contributes thousands of new neurons each day

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

    PubMed Central

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

    2014-01-01

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

  13. Combining adult stem cells and olfactory ensheathing cells: the secretome effect.

    PubMed

    Silva, Nuno A; Gimble, Jeffrey M; Sousa, Nuno; Reis, Rui L; Salgado, António J

    2013-04-15

    Adipose-derived adult stem cells (ASCs), bone marrow mesenchymal stem cells (bmMSCs), and human umbilical cord perivascular cells (HUCPVCs) tissue have been widely tested for regenerative applications, such as bone regeneration. Moreover, olfactory ensheathing cells (OECs) show promise in promoting spinal cord injury (SCI) regeneration. Our group recently proposed the use of a hybrid scaffold targeting both vertebral bone repair and SCI regeneration. According to this concept, both MSCs and OECs should be in close contact to be influenced by the factors that are involved in secretion. For this reason, here we studied the effects of the OEC secretome on the metabolic activity and proliferation of ASCs, bmMSCs, and HUCPVCs. The stem cells' secretome effects on metabolic activity and proliferation of the OECs were also considered. In co-cultures of OECs with ASCs, bmMSCs, or HUCPVCs, the metabolic activity/viability, proliferation, and total cell numbers were measured after 2 and 7 days of culture. The results demonstrated that the secretome of OECs has a positive effect on the metabolic activity and proliferation of MSCs from different origins, especially on ASCs. Furthermore, in general, the stem cells' secretome also had a positive effect on the OECs behavior, particularly when ASCs were in co-culture with OECs. These results suggest that the most suitable combination of cells to be used in our hybrid scaffold is the OECs with the ASCs. Finally, this work adds new knowledge to the cell therapy field, bringing new information about paracrine interactions between OECs and distinct mesenchymal stems. PMID:23316915

  14. Cell Stem Cell Clinical Progress

    E-print Network

    Zandstra, Peter W.

    Cell Stem Cell Clinical Progress Rapid Expansion of Human Hematopoietic Stem Cells by Automated implementations of hematopoietic stem cells (HSCs) and their deriva- tives further increase interest in strategies the marked improvements that control of feed- back signaling can offer primary stem cell culture

  15. Stem Cell 101 What is a stem cell?

    E-print Network

    Minnesota, University of

    Stem Cell 101 What is a stem cell? A stem cell is a parent cell in the body that has two specific into all types of tissue in the body ­ this is called differentiation. Where are stem cells found? There are two types of stem cells: embryonic stem cells, found in embryos, and adult stem cells, which can

  16. Stem cells in urology

    Microsoft Academic Search

    Tamer Aboushwareb; Anthony Atala

    2008-01-01

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

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

    Microsoft Academic Search

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

    2006-01-01

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

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

    EPA Science Inventory

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

  19. Effect of silver nanoparticles on human mesenchymal stem cell differentiation

    PubMed Central

    Diendorf, Jörg; Epple, Matthias; Schildhauer, Thomas A; Köller, Manfred

    2014-01-01

    Summary Background: Silver nanoparticles (Ag-NP) are one of the fastest growing products in nano-medicine due to their enhanced antibacterial activity at the nanoscale level. In biomedicine, hundreds of products have been coated with Ag-NP. For example, various medical devices include silver, such as surgical instruments, bone implants and wound dressings. After the degradation of these materials, or depending on the coating technique, silver in nanoparticle or ion form can be released and may come into close contact with tissues and cells. Despite incorporation of Ag-NP as an antibacterial agent in different products, the toxicological and biological effects of silver in the human body after long-term and low-concentration exposure are not well understood. In the current study, we investigated the effects of both ionic and nanoparticulate silver on the differentiation of human mesenchymal stem cells (hMSCs) into adipogenic, osteogenic and chondrogenic lineages and on the secretion of the respective differentiation markers adiponectin, osteocalcin and aggrecan. Results: As shown through laser scanning microscopy, Ag-NP with a size of 80 nm (hydrodynamic diameter) were taken up into hMSCs as nanoparticulate material. After 24 h of incubation, these Ag-NP were mainly found in the endo-lysosomal cell compartment as agglomerated material. Cytotoxicity was observed for differentiated or undifferentiated hMSCs treated with high silver concentrations (?20 µg·mL?1 Ag-NP; ?1.5 µg·mL?1 Ag+ ions) but not with low-concentration treatments (?10 µg·mL?1 Ag-NP; ?1.0 µg·mL?1 Ag+ ions). Subtoxic concentrations of Ag-NP and Ag+ ions impaired the adipogenic and osteogenic differentiation of hMSCs in a concentration-dependent manner, whereas chondrogenic differentiation was unaffected after 21 d of incubation. In contrast to aggrecan, the inhibitory effect of adipogenic and osteogenic differentiation was confirmed by a decrease in the secretion of specific biomarkers, including adiponectin (adipocytes) and osteocalcin (osteoblasts). Conclusion: Aside from the well-studied antibacterial effect of silver, little is known about the influence of nano-silver on cell differentiation processes. Our results demonstrate that ionic or nanoparticulate silver attenuates the adipogenic and osteogenic differentiation of hMSCs even at non-toxic concentrations. Therefore, more studies are needed to investigate the effects of silver species on cells at low concentrations during long-term treatment. PMID:25551033

  20. Umbilical Cord Stem Cells

    Microsoft Academic Search

    Kathy E. Mitchell

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

  1. Characterization and spinal fusion effect of rabbit mesenchymal stem cells

    PubMed Central

    2013-01-01

    Background The surface markers of mesenchymal stem cells (MSCs) of rabbits have been reported only sporadically. However, interest in the spinal fusion effect of MSCs has risen recently. The purpose of this research was to study the surface markers and spinal fusion effect of rabbit MSCs. Results Of our rabbit MSCs, 2% expressed CD14, CD29, and CD45, 1% expressed CD90 and 97% expressed CD44. These results implied the MSCs were negative for CD14, CD29, CD45, and CD90, but positive for CD44. The surgical results showed that satisfactory fusion occurred in 10 rabbits (83%) in the study group and unsatisfactory fusion in 2 (17%). In the control group, satisfactory fusion was found in 3 rabbits (25%) and unsatisfactory fusion in 9 (75%). Statistical analysis showed the study group had significantly better spinal fusion results than the control group. Conclusions The surface markers of human and rabbit MSCs are not exactly the same. Rabbit MSCs do not have positive reactivity for CD29 and CD90, which are invariably present on human MSCs. The allogeneic undifferentiated rabbit MSCs were able to promote spinal fusion and did not induce an adverse immune response. PMID:24325928

  2. Stem cell culture engineering

    Microsoft Academic Search

    Gargi Seth; Catherine M. Verfaillie

    2005-01-01

    Stem cells have the capacity for self renewal and undergo multilineage differentiation. Stem cells isolated from both blastocysts and adult tissues represent valuable sources of cells for applications in cell therapy, drug screening and tissue engineering. While expanding stem cells in culture, it is critical to maintain their self?renewal and differentiation capacity. In generating particular cell types for specific applications,

  3. Therapeutic effects of human mesenchymal and hematopoietic stem cells on rotenone-treated parkinsonian mice.

    PubMed

    Inden, Masatoshi; Takata, Kazuyuki; Nishimura, Kaneyasu; Kitamura, Yoshihisa; Ashihara, Eishi; Yoshimoto, Kanji; Ariga, Hiroyoshi; Honmou, Osamu; Shimohama, Shun

    2013-01-01

    To appreciate the potential applications of stem cell technology in neurodegenerative diseases, including Parkinson's disease (PD), it is important to understand the characteristics of the various types of stem cells. In this study, we designed a set of experiments to compare the ability of three types of human stem cells--mesenchymal stem cells (MSCs), bone marrow CD34(+) cells (BM), and cord blood CD34(+) cells (CB)--using rotenone-treated NOD/SCID mice. Rotenone was orally administered once daily at a dose of 30 mg/kg for 56 days to induce a parkinsonian phenotype. Intravenous delivery of CB into rotenone-treated mice was slightly more beneficial than that of MSCs or BM according to both histological and behavioral analyses. Human nucleus (hNu)(+) cells, which are a specific marker of human cells, were observed in the striatum of rotenone-treated mice transplanted with stem cells. These hNu(+) cells expressed tyrosine hydroxylase (TH). Additionally, ?-synuclein(+)/TH(+) cells in the substantia nigra pars compacta decreased significantly following stem cell transplantation. Immunohistochemical analysis also revealed that chronic exposure to rotenone decreased glial cell line-derived neurotrophic factor immunoreactivity and that the reduction was improved by each stem cell transplantation. Gene expression analyses revealed that MSCs, BM, and CB expressed several neurotrophic factors. These results suggest that the beneficial effects of intravenous delivery of stem cells into rotenone-treated mice may result not only from a neurotrophic effect but also from endogenous brain repair mechanisms and the potential of intravenous delivery of stem cells derived from an autologous source for clinical applications in PD. PMID:23073839

  4. Cell Stem Cell Dear Student: Stem Cell Scientists' Advice

    E-print Network

    Cell Stem Cell Forum Dear Student: Stem Cell Scientists' Advice to the Next Generation Emily L on Stem Cells in Society, Stanford, CA 94305, USA 2Department of Family Practice, University of British@stanford.edu (C.T.S.) http://dx.doi.org/10.1016/j.stem.2013.05.007 For the field of pluripotent stem cell biology

  5. Alginate-PLL microencapsulation: effect on the differentiation of embryonic stem cells into hepatocytes.

    PubMed

    Maguire, Tim; Novik, Eric; Schloss, Rene; Yarmush, Martin

    2006-02-20

    The emergence of hepatocyte based clinical and pharmaceutical technologies, has been limited by the absence of a stable hepatocyte cell source. Embryonic stem cells may represent a potential solution to this cell source limitation problem since they are highly proliferative, renewable, and pluripotent. Although many investigators have described techniques to effectively differentiate stem cells into a variety of mature cell lineages, their practicality is limited by: (1) low yields of fully differentiated cells, (2) absence of large scale processing considerations, and (3) ineffective downstream enrichment protocols. Thus, a differentiation platform that may be modified to induce and sustain differentiated cell function and scaled to increase differentiated cell yield would improve current stem cell differentiation strategies. Microencapsulation provides a vehicle for the discrete control of key cell culture parameters such as the diffusion of growth factors, metabolites, and wastes. In addition, both cell seeding density and bead composition may be manipulated. In order to assess the feasibility of directing stem cell differentiation via microenvironment regulation, we have developed a murine embryonic stem cell (ES) alginate poly-l-lysine microencapsulation hepatocyte differentiation system. Our results indicate that the alginate microenvironment maintains cell viability, is conducive to ES cell differentiation, and maintains differentiated cellular function. This system may ultimately assist in developing scalable stem cell differentiation strategies. PMID:16345081

  6. Effect of F68 on cryopreservation of mesenchymal stem cells derived from human tooth germ.

    PubMed

    Do?an, Ay?egül; Yalvaç, Mehmet Emir; Y?lmaz, Aysu; Rizvanov, Albert; Sahin, Fikrettin

    2013-12-01

    The use of stem-cell-based therapies in regenerative medicine and in the treatment of disorders such as Parkinson, Alzheimer's disease, diabetes, spinal cord injuries, and cancer has been shown to be promising. Among all stem cells, mesenchymal stem cells (MSCs) were reported to have anti-apoptotic, immunomodulatory, and angiogenic effects which are attributed to the restorative capacity of these cells. Human tooth germ stem cells (HTGSCs) having mesenchymal stem cell characteristics have been proven to exert high proliferation and differentiation capacity. Unlike bone-marrow-derived MSCs, HTGSCs can be easily isolated, expanded, and cryopreserved, which makes them an alternative stem cell source. Regardless of their sources, the stem cells are exposed to physical and chemical stresses during cryopreservation, hindering their therapeutic capacity. Amelioration of the side effects of cryopreservation on MSCs seems to be a priority in order to maximize the therapeutic efficacy of these cells. In this study, we tested the effect of Pluronic 188 (F68) on HTGSCs during long-term cryopreservation and repeated freezing and defrosting cycles. Our data revealed that F68 has a protective role on survival and differentiation of HTGSCs in long-term cryopreservation. PMID:23999741

  7. An opposite effect of the CDK inhibitor, p18(INK4c) on embryonic stem cells compared with tumor and adult stem cells.

    PubMed

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

    2012-01-01

    Self-renewal is a feature common to both adult and embryonic stem (ES) cells, as well as tumor stem cells (TSCs). The cyclin-dependent kinase inhibitor, p18(INK4c), is a known tumor suppressor that can inhibit self-renewal of tumor cells or adult stem cells. Here, we demonstrate an opposite effect of p18 on ES cells in comparison with teratoma cells. Our results unexpectedly showed that overexpression of p18 accelerated the growth of mouse ES cells and embryonic bodies (EB); on the contrary, inhibited the growth of late stage teratoma. Up-regulation of ES cell markers (i.e., Oct4, Nanog, Sox2, and Rex1) were detected in both ES and EB cells, while concomitant down-regulation of various differentiation markers was observed in EB cells. These results demonstrate that p18 has an opposite effect on ES cells as compared with tumor cells and adult stem cells. Mechanistically, expression of CDK4 was significantly increased with overexpression of p18 in ES cells, likely leading to a release of CDK2 from the inhibition by p21 and p27. As a result, self-renewal of ES cells was enhanced. Our current study suggests that targeting p18 in different cell types may yield different outcomes, thereby having implications for therapeutic manipulations of cell cycle machinery in stem cells. PMID:23049777

  8. Effects of Wnt3a on proliferation and differentiation of human epidermal stem cells

    SciTech Connect

    Jia Liwei; Zhou Jiaxi; Peng Sha; Li Juxue [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101 (China); Graduate School of the Chinese Academy of Sciences, 19 Yu-quan Road, Beijing 100039 (China); Cao Yujing [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101 (China); Duan Enkui [State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101 (China)], E-mail: duane@ioz.ac.cn

    2008-04-11

    Epidermal stem cells maintain development and homeostasis of mammalian epidermis throughout life. However, the molecular mechanisms involved in the proliferation and differentiation of epidermal stem cells are far from clear. In this study, we investigated the effects of Wnt3a and Wnt/{beta}-catenin signaling on proliferation and differentiation of human fetal epidermal stem cells. We found both Wnt3a and active {beta}-catenin, two key members of the Wnt/{beta}-catenin signaling, were expressed in human fetal epidermis and epidermal stem cells. In addition, Wnt3a protein can promote proliferation and inhibit differentiation of epidermal stem cells in vitro culture. Our results suggest that Wnt/{beta}-catenin signaling plays important roles in human fetal skin development and homeostasis, which also provide new insights on the molecular mechanisms of oncogenesis in human epidermis.

  9. Effect of Fatty Acids on Human Bone Marrow Mesenchymal Stem Cell Energy Metabolism and Survival

    PubMed Central

    Fillmore, Natasha; Huqi, Alda; Jaswal, Jagdip S.; Mori, Jun; Paulin, Roxane; Haromy, Alois; Onay-Besikci, Arzu; Ionescu, Lavinia; Thébaud, Bernard; Michelakis, Evangelos; Lopaschuk, Gary D.

    2015-01-01

    Successful stem cell therapy requires the optimal proliferation, engraftment, and differentiation of stem cells into the desired cell lineage of tissues. However, stem cell therapy clinical trials to date have had limited success, suggesting that a better understanding of stem cell biology is needed. This includes a better understanding of stem cell energy metabolism because of the importance of energy metabolism in stem cell proliferation and differentiation. We report here the first direct evidence that human bone marrow mesenchymal stem cell (BMMSC) energy metabolism is highly glycolytic with low rates of mitochondrial oxidative metabolism. The contribution of glycolysis to ATP production is greater than 97% in undifferentiated BMMSCs, while glucose and fatty acid oxidation combined only contribute 3% of ATP production. We also assessed the effect of physiological levels of fatty acids on human BMMSC survival and energy metabolism. We found that the saturated fatty acid palmitate induces BMMSC apoptosis and decreases proliferation, an effect prevented by the unsaturated fatty acid oleate. Interestingly, chronic exposure of human BMMSCs to physiological levels of palmitate (for 24 hr) reduces palmitate oxidation rates. This decrease in palmitate oxidation is prevented by chronic exposure of the BMMSCs to oleate. These results suggest that reducing saturated fatty acid oxidation can decrease human BMMSC proliferation and cause cell death. These results also suggest that saturated fatty acids may be involved in the long-term impairment of BMMSC survival in vivo. PMID:25768019

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  11. Cell Stem Cell Brief Report

    E-print Network

    Church, George M.

    Cell Stem Cell Brief Report Reprogramming of T Cells from Human Peripheral Blood Yuin-Han Loh,1,2,5,9,10,* 1Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA 2Harvard Stem Cell Institute, Cambridge, MA 02138, USA 3

  12. Therapeutic effects of induced pluripotent stem cells in chimeric mice with ?-thalassemia

    PubMed Central

    Yang, Guanheng; Shi, Wansheng; Hu, Xingyin; Zhang, Jingzhi; Gong, Zhijuan; Guo, Xinbing; Ren, Zhaorui; Zeng, Fanyi

    2014-01-01

    Although ?-thalassemia is one of the most common human genetic diseases, there is still no effective treatment other than bone marrow transplantation. Induced pluripotent stem cells have been considered good candidates for the future repair or replacement of malfunctioning organs. As a basis for developing transgenic induced pluripotent stem cell therapies for thalassemia, ?654 induced pluripotent stem cells from a ?654 -thalassemia mouse transduced with the normal human ?-globin gene, and the induced pluripotent stem cells with an erythroid-expressing reporter GFP were used to produce chimeric mice. Using these chimera models, we investigated changes in various pathological indices including hematologic parameters and tissue pathology. Our data showed that when the chimerism of ?654 induced pluripotent stem cells with the normal human ?-globin gene in ?654 mice is over 30%, the pathology of anemia appeared to be reversed, while chimerism ranging from 8% to 16% provided little improvement in the typical ?-thalassemia phenotype. Effective alleviation of thalassemia-related phenotypes was observed when chimerism with the induced pluripotent stem cells owning the erythroid-expressing reporter GFP in ?654 mouse was greater than 10%. Thus, 10% or more expression of the exogenous normal ?-globin gene reduces the degree of anemia in our ?-thalassemia mouse model, whereas treatment with ?654 induced pluripotent stem cells which had the normal human ?-globin gene had stable therapeutic effects but in a more dose-dependent manner. PMID:24816238

  13. Cell Stem Cell Molecular Analysis of Stem Cells and Their

    E-print Network

    Alvarado, Alejandro Sánchez

    mediterranea provide an interesting model for studying both stem cell function and line- age commitment duringCell Stem Cell Article Molecular Analysis of Stem Cells and Their Descendants during Cell Turnover@neuro.utah.edu DOI 10.1016/j.stem.2008.07.002 SUMMARY In adult planarians, the replacement of cells lost

  14. Dose rate effects on the survival of normal hematopoietic stem cells cells of BALB\\/c mice

    Microsoft Academic Search

    Glenn P. Glasgow; Karen L. Beetham; William B. Mill

    1983-01-01

    The use of total body irradiation (TBI) to ablate malignant stem cells in leukemia patients prior to bone marrow transplantation and the use of hemibody irradiation (HBI) for treating osseous metastases have focused attention on the dose rate effects, if any, exhibited by normal or malignant hematopoietic stem cells. Using male BALB\\/c mice 10 to 12 weeks old, we investigated

  15. Hair Follicle Stem Cells

    Microsoft Academic Search

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

    2003-01-01

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

  16. Cell Fusion and Stem Cells

    Microsoft Academic Search

    Alain Silk; Anne E. Powell; Paige S. Davies; Melissa H. Wong

    \\u000a Differentiation, self-renewal and the ability to readily undergo cell fusion are properties of adult and embryonic stem cells.\\u000a Spontaneous fusion between stem cells, and fusion of stem cells with various differentiated cell types, has been observed\\u000a in many in vitro and in vivo contexts. Stem cell fusion is implicated in many crucial functions during normal development\\u000a and is increasingly being

  17. Stem Cell Quick Guide: Stem Cell Basics What is a Stem Cell?

    E-print Network

    Schladow, S. Geoffrey

    Stem Cell Quick Guide: Stem Cell Basics What is a Stem Cell? Stem cells are the starting point from to line blood vessels. All of these highly specialized cells have to grow from unspecialized stem cells. Stem cells produce new cells by dividing. In the right conditions, these new cells can then continue

  18. Cell Stem Cell Protocol Review

    E-print Network

    neurons might be re- placed. As the identity of ``true'' CNS stem cells, defined as being capableCell Stem Cell Protocol Review Everything that Glitters Isn't Gold: A Critical Review of Postnatal School and Massachusetts General Hospital, Boston, MA 02114, USA 6Department of Stem Cell

  19. Cell Stem Cell Control of Stem Cell Fate by Physical

    E-print Network

    Chen, Christopher S.

    Cell Stem Cell Review Control of Stem Cell Fate by Physical Interactions with the Extracellular, Philadelphia, PA 19104, USA 5Stem Cell Laboratory, Pennington Biomedical Research Center, Louisiana State.06.016 A diverse array of environmental factors contributes to the overall control of stem cell activity

  20. Cell Stem Cell Stem Cell Epigenetics: Looking Forward

    E-print Network

    Sander, Maike

    Cell Stem Cell Voices Stem Cell Epigenetics: Looking Forward Epigenetics in Adult SCs The integrity of tissues is maintained by adult stem cells during adulthood. How- ever, recent work indicates that tissues often contain more than one population of stem cells that are located at distinct niches and display

  1. Understanding Embryonic Stem Cells

    NSDL National Science Digital Library

    Douglas A. Melton, Ph.D. (Howard Hughes Medical Institute; )

    2008-04-10

    This indexed webcast video along with synchronized lecture slides is from Howard Hughes Medical Institute's 2006 Holiday LecturesPotent Biology: Stem Cells, Cloning, and Regeneration. Douglas A. Melton presents an introduction to stem cells, as well as answers to questions about the role of stem cells in the human body. This video requires RealPlayer 10.

  2. Wnt signaling regulates the stemness of lung cancer stem cells and its inhibitors exert anticancer effect on lung cancer SPC-A1 cells.

    PubMed

    Zhang, Xueyan; Lou, Yuqing; Wang, Huimin; Zheng, Xiaoxuan; Dong, Qianggang; Sun, Jiayuan; Han, Baohui

    2015-04-01

    Wnt signaling plays an important role in regulating the activity of cancer stem cells (CSCs) in a variety of cancers. In this study, we explored the role of Wnt signaling in the lung cancer stem cells (LCSCs). LCSCs were obtained by sphere culture, for which human lung adenocarcinoma cell line SPC-A1 was treated with IGF, EGF and FGF-10. The stemness of LCSCs was confirmed by immunofluorescence, and pathway analysis was performed by functional genome screening and RT-PCR. The relationship between the identified signaling pathway and the expression of the stemness genes was explored by agonist/antagonist assay. Moreover, the effects of different signaling molecule inhibitors on sphere formation, cell viability and colony formation were also analyzed. The results showed that LCSCs were successfully generated as they expressed pluripotent stem cell markers Nanog and Oct 4, and lung distal epithelial markers CCSP and SP-C, by which the phenotype characterization of stem cells can be confirmed. The involvement of Wnt pathway in LCSCs was identified by functional genome screening and verified by RT-PCR. The expression of Wnt signaling components was closely related to the expression of the Nanog and Oct 4. Furthermore, targeting Wnt signaling pathway by using different signaling molecule inhibitors can exert anticancer effects. In conclusion, Wnt signaling pathway is involved in the stemness regulation of LCSCs and might be considered as a potential therapeutic target in lung adenocarcinoma. PMID:25731617

  3. Contrasting Effects of Basic Fibroblast Growth Factor and Neurotrophin 3 on Cell Cycle Kinetics of Mouse Cortical Stem Cells

    E-print Network

    Paris-Sud XI, Université de

    Contrasting Effects of Basic Fibroblast Growth Factor and Neurotrophin 3 on Cell Cycle Kinetics-promoting effect of NT3 are linked with modifications of cell cycle kinetics in mouse cortical precursor cells. We of Mouse Cortical Stem Cells Agnčs Lukaszewicz 1 , Pierre Savatier 2 , Véronique Cortay 1 , Henry Kennedy 1

  4. 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. PMID:22404469

  5. The hematopoietic growth factor "erythropoietin" enhances the therapeutic effect of mesenchymal stem cells in Alzheimer's disease.

    PubMed

    Khairallah, M I; Kassem, L A; Yassin, N A; El Din, M A Gamal; Zekri, M; Attia, M

    2014-01-01

    Alzheimer's disease is a neurodegenerative disorder clinically characterized by cognitive dysfunction and by deposition of amyloid plaques, neurofibrillary tangles in the brain. The study investigated the therapeutic effect of combined mesenchymal stem cells and erythropoietin on Alzheimer's disease. Five groups of mice were used: control group, Alzheimer's disease was induced in four groups by a single intraperitoneal injection of 0.8 mg kg(-1) lipopolysaccharide and divided as follows: Alzheimer's disease group, mesenchymal stem cells treated group by injecting mesenchymal stem cells into the tail vein (2 x 10(6) cells), erythropoietin treated group (40 microg kg(-1) b.wt.) injected intraperitoneally 3 times/week for 5 weeks and mesenchymal stem cells and erythropoietin treated group. Locomotor activity and memory were tested using open field and Y-maze. Histological, histochemical, immunohistochemical studies, morphometric measurements were examined in brain sections of all groups. Choline transferase activity, brain derived neurotrophic factor expression and mitochondrial swellings were assessed in cerebral specimens. Lipopolysaccharide decreased locomotor activity, memory, choline transferase activity and brain derived neurotrophic factor. It increased mitochondrial swelling, apoptotic index and amyloid deposition. Combined mesenchymal stem cells and erythropoietin markedly improved all these parameters. This study proved the effective role of mesenchymal stem cells in relieving Alzheimer's disease symptoms and manifestations; it highlighted the important role of erythropoietin in the treatment of Alzheimer's disease. PMID:24783773

  6. Immunomodulatory effects of mesenchymal stem cells involved in favoring type 2 T cell subsets.

    PubMed

    Lu, Xiaoxi; Liu, Ting; Gu, Ling; Huang, Chunlan; Zhu, Huanling; Meng, Wentong; Xi, Yaming; Li, Shengfu; Liu, Yongmei

    2009-12-01

    Graft-vs.-host disease (GVHD) caused by immunologic activated cells remains a real problem in human allogeneic hematopoetic stem cell transplantation. Mesenchymal stem cells (MSCs) play some important roles on immunomodulatory. We developed a parent-into-F1 model of acute GVHD to evaluate the mechanisms involved in immunological mediated damage and the immunomodulatory effect of the MSCs on GVHD. The recipients, BABL/cxC57BL/6 (H-2(bxd)) F1 mice, received 8.5Gy total-body gamma irradiation ((6)(0)C(O)), then rescued with C57BL/6 (H-2(b)) mice (donors) bone marrow cells and induced acute GVHD by adding donor splenocytes. The MSCs culture-expanded from C57BL/6 (H-2(b)) mice were infused to recipients simultaneity in the experimental group. The severity of GVHD was evaluated by histopathologic examination of target organs including liver, intestine, and claw skin and a clinical manifestation scoring system. We analyzed the distribution of peripheral blood T cell subsets of recipients by flow cytometry and measured the expression of CXCR3 on activated T cells in target organs by immunohistochemistry staining. Our results suggested the tissue damage initiated by GVHD was significantly alleviated in the MSCs treated mice, and the proportion of type 2 T cells in peripheral blood was higher in the MSCs treated mice than in the control group. Although the overall survival rate did not significantly improved in the mice with MSCs infusion, the immunomodulatory effect of MSCs was possibly related to favor type 2 T cell subsets and decrease chemokine receptor CXCR3 expression on activated T cells. PMID:19695330

  7. Gastrointestinal Stem Cells

    Microsoft Academic Search

    N. Parveen; Aleem A. Khan; M. Aejaz Habeeb; C. M. Habibullah

    \\u000a Stem cell research is advancing at an incredible pace, with new ­discoveries and clinical applications being reported from\\u000a all over the world. Stem cells are functionally defined by their ability to self-renew and to differentiate into the cell\\u000a lineages of their tissue of origin. Stem cells are self-sustaining and can ­replicate themselves for long periods of time.\\u000a These characteristics make

  8. Stem Cell Transplants

    NSDL National Science Digital Library

    Irwin Slesnick

    2004-01-01

    Transplanting embryonic stem cells from embryo into adult as a means of rejuvenating diseased cells, tissues, and organs poses ethical and moral challenges. In recent years, stem cell-derived nerve and glandular tissue has been transplanted into the brains and pancreas of Parkinson's disease and diabetes patients, respectively, with mixed results. This chapter provides background information on stem cell research, the future treatment of Parkinson's disease, and the controversy surrounding this sensitive issue.

  9. Embryonic Stem Cells

    Microsoft Academic Search

    Victoria L. Browning; Jon S. Odorico

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

  10. Skeletal muscle stem cells

    Microsoft Academic Search

    Jennifer CJ Chen; David J Goldhamer

    2003-01-01

    Satellite cells are myogenic stem cells responsible for the post-natal growth, repair and maintenance of skeletal muscle. This review focuses on the basic biology of the satellite cell with emphasis on its role in muscle repair and parallels between embryonic myogenesis and muscle regeneration. Recent advances have altered the long-standing view of the satellite cell as a committed myogenic stem

  11. Circulating Skeletal Stem Cells

    Microsoft Academic Search

    Sergei A. Kuznetsov; Mahesh H. Mankani; Stan Gronthos; Kazuhito Satomura; Paolo Bianco; Pamela Gehron Robey

    2001-01-01

    We report the isolation of adherent, clono- genic, fibroblast-like cells with osteogenic and adipogenic potential from the blood of four mammalian species. These cells phenotypically resemble but are distinguish- able from skeletal stem cells found in bone marrow (stromal stem cells, \\

  12. The Effects of Secretion Factors from Umbilical Cord Derived Mesenchymal Stem Cells on Osteogenic Differentiation of Mesenchymal Stem Cells

    PubMed Central

    Wang, Kui-Xing; Xu, Liang-Liang; Rui, Yun-Feng; Huang, Shuo; Lin, Si-En; Xiong, Jiang-Hui; Li, Ying-Hui; Lee, Wayne Yuk-Wai; Li, Gang

    2015-01-01

    Factors synthesized by mesenchymal stem cells (MSCs) contain various growth factors, cytokines, exosomes and microRNAs, which may affect the differentiation abilities of MSCs. In the present study, we investigated the effects of secretion factors of human umbilical cord derived mesenchymal stem cells (hUCMSCs) on osteogenesis of human bone marrow derived MSCs (hBMSCs). The results showed that 20 ?g/ml hUCMSCs secretion factors could initiate osteogenic differentiation of hBMSCs without osteogenic induction medium (OIM), and the amount of calcium deposit (stained by Alizarin Red) was significantly increased after the hUCMSCs secretion factors treatment. Real time quantitative reverse transcription-polymerase chain reaction (real time qRT-PCR) demonstrated that the expression of osteogenesis-related genes including ALP, BMP2, OCN, Osterix, Col1? and Runx2 were significantly up-regulated following hUCMSCs secretion factors treatment. In addition, we found that 10 ?g hUCMSCs secretion factors together with 2×105 hBMSCs in the HA/TCP scaffolds promoted ectopic bone formation in nude mice. Local application of 10 ?g hUCMSCs secretion factors with 50 ?l 2% hyaluronic acid hydrogel and 1×105 rat bone marrow derived MSCs (rBMSCs) also significantly enhanced the bone repair of rat calvarial bone critical defect model at both 4 weeks and 8 weeks. Moreover, the group that received the hUCMSCs secretion factors treatment had more cartilage and bone regeneration in the defect areas than those in the control group. Taken together, these findings suggested that hUCMSCs secretion factors can initiate osteogenesis of bone marrow MSCs and promote bone repair. Our study indicates that hUCMSCs secretion factors may be potential sources for promoting bone regeneration. PMID:25799169

  13. The effects of secretion factors from umbilical cord derived mesenchymal stem cells on osteogenic differentiation of mesenchymal stem cells.

    PubMed

    Wang, Kui-Xing; Xu, Liang-Liang; Rui, Yun-Feng; Huang, Shuo; Lin, Si-En; Xiong, Jiang-Hui; Li, Ying-Hui; Lee, Wayne Yuk-Wai; Li, Gang

    2015-01-01

    Factors synthesized by mesenchymal stem cells (MSCs) contain various growth factors, cytokines, exosomes and microRNAs, which may affect the differentiation abilities of MSCs. In the present study, we investigated the effects of secretion factors of human umbilical cord derived mesenchymal stem cells (hUCMSCs) on osteogenesis of human bone marrow derived MSCs (hBMSCs). The results showed that 20 ?g/ml hUCMSCs secretion factors could initiate osteogenic differentiation of hBMSCs without osteogenic induction medium (OIM), and the amount of calcium deposit (stained by Alizarin Red) was significantly increased after the hUCMSCs secretion factors treatment. Real time quantitative reverse transcription-polymerase chain reaction (real time qRT-PCR) demonstrated that the expression of osteogenesis-related genes including ALP, BMP2, OCN, Osterix, Col1? and Runx2 were significantly up-regulated following hUCMSCs secretion factors treatment. In addition, we found that 10 ?g hUCMSCs secretion factors together with 2×105 hBMSCs in the HA/TCP scaffolds promoted ectopic bone formation in nude mice. Local application of 10 ?g hUCMSCs secretion factors with 50 ?l 2% hyaluronic acid hydrogel and 1×105 rat bone marrow derived MSCs (rBMSCs) also significantly enhanced the bone repair of rat calvarial bone critical defect model at both 4 weeks and 8 weeks. Moreover, the group that received the hUCMSCs secretion factors treatment had more cartilage and bone regeneration in the defect areas than those in the control group. Taken together, these findings suggested that hUCMSCs secretion factors can initiate osteogenesis of bone marrow MSCs and promote bone repair. Our study indicates that hUCMSCs secretion factors may be potential sources for promoting bone regeneration. PMID:25799169

  14. Effect of cell density on adipogenic differentiation of mesenchymal stem cells

    SciTech Connect

    Lu, Hongxu [Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 (Japan) [Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 (Japan); Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Guo, Likun [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan) [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064 (China); Wozniak, Michal J. [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan)] [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Kawazoe, Naoki [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan) [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Tateishi, Tetsuya [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan)] [Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Zhang, Xingdong [National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064 (China)] [National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064 (China); Chen, Guoping, E-mail: Guoping.CHEN@nims.go.jp [Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 (Japan) [Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 (Japan); Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan)

    2009-04-10

    The effect of cell density on the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) was investigated by using a patterning technique to induce the formation of a cell density gradient on a micropatterned surface. The adipogenic differentiation of MSCs at a density gradient from 5 x 10{sup 3} to 3 x 10{sup 4} cells/cm{sup 2} was examined. Lipid vacuoles were observed at all cell densities after 1-3 weeks of culture in adipogenic differentiation medium although the lipid vacuoles were scarce at the low cell density and abundant at the high cell density. Real-time RT-PCR analysis showed that adipogenesis marker genes encoding peroxisome proliferator-activated receptor {gamma}2 (PPAR{gamma}2), lipoprotein lipase (LPL), and fatty acid binding protein-4 (FABP4) were detected in the MSCs cultured at all cell densities. The results suggest that there was no apparent effect of cell density on the adipogenic differentiation of human MSCs.

  15. Capturing the Stem Cell Paracrine Effect Using Heparin-Presenting Nanofibers to Treat Cardiovascular Diseases

    PubMed Central

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

    2012-01-01

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

  16. Distinct effects of caudalizing factors on regional specification of embryonic stem cell-derived neural precursors

    Microsoft Academic Search

    Takashi Irioka; Kiichi Watanabe; Hidehiro Mizusawa; Kenji Mizuseki; Yoshiki Sasai

    2005-01-01

    Recent embryological studies have implicated several “caudalizing factors” in the caudal specification of the central nervous system (CNS). In this study, we have examined the effects of three candidate caudalizing factors on neural precursors induced from embryonic stem (ES) cells by the stromal cell-derived inducing activity (SDIA) method. Among retinoic acid (RA), Wnt and FGF signals, RA causes the strongest

  17. Optimizing stem cell culture

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    SciTech Connect

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

    2008-09-12

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

  20. Engineering stem cell niches in bioreactors

    PubMed Central

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “niches”, to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering. PMID:24179601

  1. Cardiac stem cell therapy

    Microsoft Academic Search

    C. Nesselmann; A. Kaminski; G. Steinhoff

    2011-01-01

    In cardiac stem cell therapy, the past decade has been interesting with respect to preclinical and clinical research. The\\u000a high diversity of applied stem cell populations and evaluation methods represent a challenge to fully understand the impact\\u000a of stem cell administration, leaving uncertain answers to the questions that have been dealt with thus far. In the present\\u000a work, registered studies

  2. Embryonic Stem Cell Course

    NSDL National Science Digital Library

    This "Course-in-a-Box" from Bio-Link is a good starting point for instructors to develop a course on embryonic stem cells. If a full course on stem cells is not appropriate for a particular curriculum "individual lectures and activity modules are well-suited for integration into existing bioscience or biotechnology courses." Materials include laboratory protocols for both mouse and human embryonic stem cells, lectures, activities, and assessments. A free login is required to access the materials.

  3. Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment

    Microsoft Academic Search

    Sung Su An; Hong Lian Jin; Keung Nyun Kim; Hyun Ah Kim; Dong Seok Kim; Joon Cho; Meng-Lu Liu; Jin Soo Oh; Do Heum Yoon; Min Hyung Lee; Yoon Ha

    2010-01-01

    Purposes  To avoid unwanted adverse effects of higher doses of single treatment of stem cells and gene therapy and increase the therapeutic\\u000a efficacies, we hypothesized the combined therapy with stem cells and gene therapy. This study assessed the neuroprotective\\u000a effects of combined gene therapy and stem cell treatment under ischemic hypoxia conditions using hypoxia-inducible vascular\\u000a endothelial growth factor (VEGF) and bone

  4. Bioreactors Stem Cells

    E-print Network

    SchĂĽler, Axel

    Keywords Bioreactors Stem Cells Regenerative Medicine Tissue Engineering Pharmacology » Prof. M.; yeZhelyev, M.; eMMrich, F.; o'regan, r.; bader, a. Quantum dots for human mesenchymal stem cells and mechanical forces mediated to the cells by the matrix. The in vivo extracellular matrix constitutes

  5. Stem Cell Resources

    NSDL National Science Digital Library

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

  6. Stem Cells, Colorectal Cancer and Cancer Stem Cell Markers Correlations

    PubMed Central

    CHERCIU, IRINA; B?RB?LAN, A.; PIRICI, D.; M?RG?RITESCU, C.; S?FTOIU, A.

    2014-01-01

    : The idea of stem cells as being progenitors of cancer was initially controversial, but later supported by research in the field of leukemia and solid tumors. Afterwards, it was established that genetic abnormalities can affect the stem and progenitor cells, leading to uncontrolled replication and deregulated differentiation. These alterations will cause the changeover to cancerous stem cells (CSC) having two main characteristics: tumor initiation and maintenance. This review will focus on the colorectal cancer stem cell (CR-CSCs) theory which provides a better understanding of different tumor processes: initiation, aggressive growth, recurrence, treatment resistance and metastasis. A search in PubMed/Medline was performed using the following keywords: colorectal cancer stem cells (CR-CSCs), colorectal neoplasms stem cells, colorectal cancer stem cell (CR-CSCs) markers, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Isolation of CR-CSCs can be achieved by targeting and selecting subpopulation of tumor cells based on expression of one or multiple cell surface markers associated with cancer self-renewal, markers as: CD133, CD166, CD44, CD24, beta1 integrin-CD29, Lgr5, EpCAM (ESA), ALDH-1, Msi-1, DCAMLK1 or EphB receptors. The identification and localization of CR-CSCs through different markers will hopefully lead to a better stratification of prognosis and treatment response, as well as the development of new effective strategies for cancer management. PMID:25729599

  7. Skeletal muscle stem cells.

    PubMed

    Kao, Grace W; Lamb, Elizabeth K; Kao, Race L

    2013-01-01

    Skeletal muscle satellite cells (myoblasts) are the primary stem cells of skeletal muscle which contribute to growth, maintenance, and repair of the muscles. Satellite cells are the first stem cells used for cellular cardiomyoplasty more than 20 years ago. The isolation, culture, labeling, and identification of satellite cells are described in detail here. The implantation and outcomes of cellular cardiomyoplasty using satellite cells have been summarized in the previous chapter (Chapter 1). PMID:23807783

  8. Effects of age and Pax6 deficiency on mouse limbal stem cell function 

    E-print Network

    Douvaras, Panagiotis

    2010-01-01

    The conventional view for corneal epithelial maintenance suggests that a stem cell population found in the limbus (at the rim of the cornea) produces daughter cells, called transient amplifying cells, which migrate centripetally. This limbal stem...

  9. 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

  10. Effect of HSA coated iron oxide labeling on human umbilical cord derived mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Sanganeria, Purva; Chandra, Sudeshna; Bahadur, Dhirendra; Khanna, Aparna

    2015-03-01

    Human umbilical cord derived mesenchymal stem cells (hUC-MSCs) are known for self-renewal and differentiation into cells of various lineages like bone, cartilage and fat. They have been used in biomedical applications to treat degenerative disorders. However, to exploit the therapeutic potential of stem cells, there is a requirement of sensitive non-invasive imaging techniques which will offer the ability to track transplanted cells, bio-distribution, proliferation and differentiation. In this study, we have analyzed the efficacy of human serum albumin coated iron oxide nanoparticles (HSA-IONPs) on the differentiation of hUC-MSCs. The colloidal stability of the HSA-IONPs was tested over a long period of time (?20 months) and the optimized concentration of HSA-IONPs for labeling the stem cells was 60 ?g ml?1. Detailed in vitro assays have been performed to ascertain the effect of the nanoparticles (NPs) on stem cells. Lactate dehydrogenase (LDH) assay showed minimum release of LDH depicting the least disruptions in cellular membrane. At the same time, mitochondrial impairment of the cells was also not observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry analysis revealed lesser generation of reactive oxygen species in HSA-IONPs labeled hUC-MSCs in comparison to bare and commercial IONPs. Transmission electron microscopy showed endocytic engulfment of the NPs by the hUC-MSCs. During the process, the gross morphologies of the actin cytoskeleton were found to be intact as shown by immunofluorescence microscopy. Also, the engulfment of the HSA-IONPs did not show any detrimental effect on the differentiation potential of the stem cells into adipocytes, osteocytes and chondrocytes, thereby confirming that the inherent properties of stem cells were maintained.

  11. 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

  12. Effect of hyperbaric oxygen on mesenchymal stem cells for lumbar fusion in vivo

    Microsoft Academic Search

    Tsai-Sheng Fu; Steve WN Ueng; Tsung-Ting Tsai; Lih-Huei Chen; Song-Shu Lin; Wen-Jer Chen

    2010-01-01

    BACKGROUND: Hyperbaric oxygen (HBO) therapy has been proved in improving bone healing, but its effects on mesenchymal stem cells (MSCs) in vivo is not clear. The aims of this study are to clarify whether the HBO therapy has the same enhancing effect on MSCs with regard to bone formation and maturation and to ascertain whether the transplanted MSCs survive in

  13. Effects of barium titanate nanoparticles on proliferation and differentiation of rat mesenchymal stem cells.

    PubMed

    Ciofani, Gianni; Ricotti, Leonardo; Canale, Claudio; D'Alessandro, Delfo; Berrettini, Stefano; Mazzolai, Barbara; Mattoli, Virgilio

    2013-02-01

    Nanomaterials hold great promise in the manipulation and treatments of mesenchymal stem cells, since they allow the modulation of their properties and differentiation. However, systematic studies have to be carried out in order to assess their potential toxicological effects. The present study reports on biocompatibility evaluation of glycol-chitosan coated barium titanate nanoparticles (BTNPs) on rat mesenchymal stem cells (MSCs). BTNPs are a class of ceramic systems which possess interesting features for biological applications thanks to their peculiar dielectric and piezoelectric properties. Viability was evaluated up to 5 days of incubation (concentrations in the range 0-100 ?g/ml) both quantitatively and qualitatively with specific assays. Interactions cells/nanoparticles were further investigated with analysis of the cytoskeleton conformation, with SEM and TEM imaging, and with AFM analysis. Finally, differentiation in adipocytes and osteocytes was achieved in the presence of high doses of BTNPs, thus highlighting the safety of these nanostructures towards mesenchymal stem cells. PMID:23006571

  14. Effect of temozolomide on livin and caspase-3 in U251 glioma stem cells

    PubMed Central

    LI, GENHUA; ZHANG, HAO; LIU, YANG; KONG, LINGSHENG; GUO, QIANG; JIN, FENG

    2015-01-01

    The aim of the present study was to analyze the effect of temozolomide (TMZ) on the antiapoptotic gene livin and the associated gene caspase-3. Cancer stem cells were isolated from U251 glioblastoma cells using immunomagnetic beads. The glioma cells and glioma stem cells were transfected with livin or small hairpin RNA (shRNA) against livin using lentiviral vectors. Quantitative PCR, flow cytometry and a Cell Counting kit-8 assay were used to detect the expression of livin and caspase-3, analyze the cell cycle and investigate cell proliferation, respectively, following treatment with various concentrations of TMZ (0, 25, 50, 100, 200 and 400 ?mol/l) for different periods of time (24, 48 and 72 h). The expression levels of livin and caspase-3 in the U251 stem cells were significantly higher than those in the U251 cells (P<0.01). At the same intervention time, the expression levels of livin decreased and those of caspase-3 increased as the concentration of TMZ increased (P<0.05). The expression levels of livin and caspase-3 in the U251 cells were lower than those in the U251 stem cells with the same intervention time and concentration of TMZ (P<0.05). The cell cycle was arrested in the G2/M phase in the U251 cells following TMZ intervention; the proportion of cells in the G2/M phase increased as the concentration of TMZ increased (P<0.05). The U251 stem cells were arrested in the S phase following treatment with TMZ; the proportion of cells in the S phase increased as the concentration of TMZ increased (P<0.05). In conclusion, the expression levels of livin and caspase-3 were effectively inhibited and increased, respectively, in all cell models following treatment with TMZ. TMZ is able to arrest the cell cycle and enhance cell apoptosis. U251 stem cells are less vulnerable than U251 cells to TMZ. PMID:25667622

  15. CD14 + monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

    Microsoft Academic Search

    Ding Wang; Ke Chen; Wei Ting Du; Zhi-Bo Han; He Ren; Ying Chi; Shao Guang Yang; Francis Bayard; Delin Zhu; Zhong Chao Han

    2010-01-01

    Here, the effect of CD14+ monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-? (IFN-?) secretion capacities of CD4+ and CD8+ T cells in response to anti-CD3\\/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of

  16. Effects of salinomycin on human bone marrow-derived mesenchymal stem cells in vitro.

    PubMed

    Scherzed, A; Hackenberg, S; Froelich, K; Rak, K; Technau, A; Radeloff, A; Nöth, U; Koehler, C; Hagen, R; Kleinsasser, N

    2013-04-26

    Various hypotheses on the origin of cancer stem cells (CSCs) exist, including that CSCs develop from transformed human bone marrow mesenchymal stem cells (hBMSC). Since the polyether antibiotic salinomycin selectively kills CSCs, the present study aims to elucidate the effects of salinomycin on normal hBMSC. The immunophenotype of hBMSC after salinomycin exposure was observed by flow cytometry. The multi-differentiation capacity of hBMSC was evaluated by Oil Red O and van Kossa staining. Cytotoxic effects of salinomycin were monitored by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay. Furthermore, spheroid formation and migration capacity were assessed. There were no differences in the immunophenotype and multi-differentiation capacity of hBMSC induced by salinomycin treatment. Cytotoxic effects were observed at concentrations of 30 ?M and above. Neither the migration capability nor the ability to form spheroids was affected. Essential functional properties of hBMSC were unaffected by salinomycin. However, dose-dependent cytotoxicity effects could be observed. Overall, low dose salinomycin showed no negative effects on hBMSC. Since mesenchymal stem cells from various sources respond differently, further in vitro studies are needed to clarify the effect of salinomycin on tissue-specific stem cells. PMID:23410960

  17. Donating Peripheral Blood Stem Cells

    MedlinePLUS

    ... this page Print this page Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... PBSC Donating bone marrow Donor experiences Peripheral blood stem cell (PBSC) donation is one of two methods of ...

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

    Microsoft Academic Search

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

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

  19. Molecular effect of ethanol during neural differentiation of human embryonic stem cells in vitro.

    PubMed

    Kim, Jeffrey J; Duan, Lewei; Tu, Thanh G; Elie, Omid; Kim, Yiyoung; Mathiyakom, Nathan; Elashoff, David; Kim, Yong

    2014-12-01

    Potential teratogenic effects of alcohol on fetal development have been documented. Especially studies have demonstrated deleterious effect of ethanol exposure on neuronal development in animal models and on the maintenance and differentiation of neuronal precursor cells derived from stem cells. To better understand molecular effect of alcohol on the process of neural differentiation, we have performed gene expression microarray analysis on human embryonic stem cells being directed to neural rosettes and neural precursor cells in the presence of ethanol treatment. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE56906. Our data provide scientific insight on potential molecular effects of fetal alcohol exposure on neural differentiation of early embryo development. PMID:25089259

  20. Effect of arsenic compounds on the in vitro differentiation of mouse embryonic stem cells into cardiomyocytes.

    PubMed

    Wang, Qian Qian; Lan, Yong Fei; Rehman, Kanwal; Jiang, Yu Han; Maimaitiyiming, Yasen; Zhu, Dan Yan; Naranmandura, Hua

    2015-03-16

    Arsenic is a known carcinogen; however, there is no information on the toxic effects of inorganic arsenic and its intermediate metabolites, monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), during the differentiation of embryonic stem (ES) cells into cardiomyocytes. The objective of this study was to evaluate the effects of arsenic compounds on ES cell differentiation into cardiomyocytes in vitro and to predict the associated toxic effects. Although iAs(III) is known to be toxic, here we found that iAs(III) and DMA(III) did not influence ES cellular differentiation, whereas MMA(III) inhibited ES cell differentiation into cardiomyocytes, suggesting that MMA(III) has adverse effects on embryonic stem cells. PMID:25166275

  1. Stem Cell Differentiation Game

    NSDL National Science Digital Library

    2013-07-30

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

  2. Bone marrow stem cells.

    PubMed

    Duong, Minh Ngoc; Ma, Yu-Ting; Chiu, Ray C J

    2013-01-01

    The "mesenchymal stem cells (MSCs)" are cells adherent in the bone marrow, which can be isolated to induce differentiation. In contrast to the "embryonic stem cells" whose goal is to develop a new organism, the "MSC adult stem cells" can participate in tissue growth and repair throughout postnatal life. Addition of 5-azacytidine to MSCs in vitro induces the gradual increase in cellular size and begins spontaneous beatings, thereafter differentiating into cardiomyocytes. The "Methods" and "Protocols" to induce structural and functional maturations of MSCs, thus to achieve "Cellular Cardiomyoplasty," are described. With appropriate media, differentiations of MSCs to various kinds of cells such as chondrocytes, osteocytes, and adipocytes are also achievable. PMID:23807784

  3. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Askari, Arman T.; Unzek, Samuel; Popovic, Zoran B.; Goldman, Corey K.; Forudi, Farhad; Kiedrowski, Matthew; Rovner, Aleksandr; Ellis, Stephen G.; Thomas, James D.; DiCorleto, Paul E.; Topol, Eric J.; Penn, Marc S.

    2003-01-01

    BACKGROUND: Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy. METHODS: We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography. FINDINGS: Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, p<0.02) resulting in greater left-ventricular mass (1.24 [0.29] vs 1.57 [0.27] g) and better cardiac function (shortening fraction 9.2 [4.9] vs 17.2 [4.2]%, n=8 per group, p<0.05). INTERPRETATION: These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is re-established.

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

    PubMed Central

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

    2014-01-01

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

  5. In vitro Osteogenic impulse effect of Dexamethasone on periodontal ligament stem cells

    PubMed Central

    Roozegar, Mohamad Ali; Mohammadi, Tayebeh Malek; Havasian, Mohamad Reza; Panahi, Jafar; Hashemian, Amirreza; Amraei, Mansur; Hoshmand, Behzad

    2015-01-01

    Periodontium is a complex organ composed of mineralized epithelial and connective tissue. Dexamethasone could stimulate proliferation of osteoblast and fibroblasts. This study aimed to assess the osteogenic effect of dexamethasone on periodental ligament (PDL) stem cells. PDL stem cells were collected from periodontal ligament tissue of root of extracted premolar of young and healthy people. The stem cells were cultured in ?-MEM Medium in three groups, one group with basic medium contains (?- MEM and FBS 10 % and 50 mmol of ?_ gelisrophosphat and L_ ascorbic acid µg/ml), the second group: basic medium with dexamethasone and the third one: basic medium without any osteogenic stimulant. Mineralization of cellular layer was analyzed with Alizarin red stain method. Osteogenic analysis was done by Alkaline phosphates and calcium test. These analysis indicated that the amount of intra-cellular calcium and alkaline phosphates in the Dexamethasone group was far more than the control and basic group (P<0.05). The results of Alizarin red stain indicated more mineralization of cultured cells in Dexamethasone group (P<0.05). The study results showed that Dexamethasone has significant osteogenic effect on PDL stem cells and further studies are recommended to evaluate its effect on treatment of bone disorders.

  6. Effects of stem cell factor on the growth and radiation survival of tumor cells.

    PubMed

    Shui, C; Khan, W B; Leigh, B R; Turner, A M; Wilder, R B; Knox, S J

    1995-08-01

    Recombinant human stem cell factor (SCF) binds to the c-kit receptor on human bone marrow progenitor cells and enhances their survival following irradiation. Since the c-kit receptor has also been detected on malignant cells, experiments were performed to study the effect of SCF on the proliferation and radiation survival of a variety of both c-kit-positive and -negative human tumor cell lines using [3H]thymidine incorporation and colony formation assays. The addition of SCF to both c-kit-positive and -negative cell line cultures had no significant effect on the stimulation index (in [3H]thymidine assay). In contrast, colony formation by H69 (small cell lung cancer cell line), H128 (small cell lung cancer cell line), and HEL (erythroid leukemia cell line) cells was enhanced by SCF in a dose-dependent manner, but SCF did not promote the in vivo growth of H128 xenograft tumors in terms of graft rate, time from implantation to tumor detection, or tumor size. Furthermore, SCF did not significantly increase the surviving fraction of either c-kit-positive or -negative cell lines following radiation, and there were no statistically significant differences between D0 [defined by the slope of the terminal exponential region of the two-component (single-hit multitarget model) survival curve where slope = 1/D0], Dq (quasithreshold dose), n (extrapolation number), alpha, and beta values for any of the cell lines studied that were irradiated with and without SCF. Finally, nude mice with transplanted human LG425 cutaneous T-cell lymphoma (c-kit positive) were treated with 10 Gy with or without SCF (100 micrograms/kg i.p. 20 h before, 2 h before, and 4 h after irradiation). There were no significant differences in the median tumor quadrupling time between groups that received either no treatment or SCF alone, or between groups treated with 10 Gy and SCF or 10 Gy alone (P > 0.05). These results are encouraging and suggest that SCF does not stimulate tumor cell proliferation in vivo or enhance the survival of tumor cells following irradiation. PMID:7542170

  7. Mesenchymal stem cells.

    PubMed

    Ding, Dah-Ching; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2011-01-01

    Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases. PMID:21396235

  8. Neurogenic Effect of  Amyloid Peptide in the Development of Neural Stem Cells

    Microsoft Academic Search

    Miguel A. Lopez-Toledano; Michael L. Shelanski

    2004-01-01

    The adult mammalian brain contains neural stem cells (NSCs) with self-renewal and multilineage potential in the hippocampus and subventricular zone. However, neurogenesis from these areas does not compensate for neuronal loss in age-related neurodegenerative disorders such as Alzheimer's disease (AD). To test whether an impairment of neurogenesis could contribute to the pathogenesis of AD, we examined the effects of amyloid-

  9. Figure 1: Multiplex logarithmic microfluidic perfusion array for probing shear stress effects on stem cells. (A)

    E-print Network

    Voldman, Joel

    Figure 1: Multiplex logarithmic microfluidic perfusion array for probing shear stress effects on stem cells. (A) Microfluidic perfusion systems exhibit more defined shear stress profiles and consume. (B) A 1x6 multiplex logarithmic microfluidic array for simultaneous application of shear stress

  10. Late effects after stem cell transplantation (SCT) in children – growth and hormones

    Microsoft Academic Search

    M B Ranke; C P Schwarze; R Dopfer; T Klingebiel; H-G Scheel-Walter; P Lang; D Niethammer

    2005-01-01

    Stem cell transplantation (SCT) has established itself as a very successful therapy in often otherwise unbeatable disorders. In a subset of children and adolescents there are, however, late effects, often as a combination of the underlying disorder, its primary treatment and subsequent SCT. In children and adolescents, disorders of growth and the endocrine system have been observed to occur frequently.

  11. Interaction between stem cell factor and endothelin-1: effects on melanogenesis in human skin xenografts

    Microsoft Academic Search

    Penkanok Sriwiriyanont; Atsushi Ohuchi; Akira Hachiya; Marty O Visscher; Raymond E Boissy

    2006-01-01

    The two paracrine melanogenic cytokines, stem cell factor (SCF) and endothelin-1 (ET-1), have been demonstrated to play pivotal roles in skin pigmentation including UVB-induced pigmentation and senile lentigo. However, little is known regarding their interactive effect on skin pigmentation. In order to investigate their roles in vivo, facultative pigmentation of human skin xenografts on severe combined immunodeficient (SCID) mice was

  12. LETTER doi:10.1038/nature12830 Oncogenic Nras has bimodal effects on stem cells

    E-print Network

    Cai, Long

    LETTER doi:10.1038/nature12830 Oncogenic Nras has bimodal effects on stem cells that sustainably allele of oncogenic NrasG12D increases HSC pro- liferationbutalsoincreasesreconstitutingandself­5 . Many oncogenic mutations increase HSC proliferation but deplete HSCs, preventing clonal expansion6

  13. Lgr proteins in epithelial stem cell biology.

    PubMed

    Barker, Nick; Tan, Shawna; Clevers, Hans

    2013-06-01

    The ultimate success of global efforts to exploit adult stem cells for regenerative medicine will depend heavily on the availability of robust, highly selective stem cell surface markers that facilitate the isolation of stem cells from human tissues. Any subsequent expansion or manipulation of isolated stem cells will also require an intimate knowledge of the mechanisms that regulate these cells, to ensure maintenance of their regenerative capacities and to minimize the risk of introducing undesirable growth traits that could pose health risks for patients. A subclass of leucine-rich repeat-containing G-protein-coupled receptor (Lgr) proteins has recently gained prominence as adult stem cell markers with crucial roles in maintaining stem cell functions. Here, we discuss the major impact that their discovery has had on our understanding of adult stem cell biology in various self-renewing tissues and in accelerating progress towards the development of effective stem cell therapies. PMID:23715542

  14. Governing stem cell fate through inert materials

    Microsoft Academic Search

    Paolo Di Nardo; Marilena Minieri

    2011-01-01

    A decade of intensive research has not produced consistent results able to allow a safe and cost-effective use of stem cells in the clinical setting. Among the different causes, the vision that the stem cell rejuvenating potential could overwhelm all the other biological cues has demonstrated to be very weak. Instead, it is now clear that stem cell fate is

  15. The inhibitory effect of hypoxic cytotoxin on the expansion of cancer stem cells in ovarian cancer.

    PubMed

    Nozawa-Suzuki, Noriko; Nagasawa, Hideko; Ohnishi, Ken; Morishige, Ken-Ichirou

    2015-02-20

    While an increase in progression free survival time is seen when an angiogenesis inhibitor is used in the treatment of high-relapse rate ovarian cancer, it has little effect on overall survival. A possible cause of treatment-resistance to angiogenesis inhibitors is the growth of stem cells in a hypoxic microenvironment built inside the tumor tissue by angiogenesis inhibition. In this study, we examined the possible suppression of stem cell and cancer stem cell (CSC) expansion by hypoxic cytotoxin, TX-402. TX-402, an analogue of tirapazamine, has been developed as a hypoxia selective prodrug with inhibitory effects of HIF-1 and angiogenesis. We considered TX-402 as a possible molecular-target drug candidate for ovarian cancer due to its inhibition of CSC expansion. In this study, we found that the expressions of HIF-1? and HIF-2? were increased under hypoxia in serous ovarian cancer cell lines. The expressions of HIF-1? and HIF-2? induced under hypoxia were repressed by TX-402 in a dose-dependent manner. Next, we investigated the effects of hypoxia on the expression levels of stem cell factors, Oct4, Nanog, Sox2 and Lin28, and showed that their expressions were induced by hypoxia. It was also observed that the expressions of putative ovarian cancer stem cell markers, CD133 and CD44 were induced under hypoxia. Furthermore, TX-402 was found to dose-dependently inhibit the expressions of CSC markers and stem cell factors. Oct4 expression was repressed by HIF-2? silencing, but not by HIF-1? silencing, indicating that TX-402 may repress the expression of Oct4 by inhibiting HIF-2?. We constructed CaOV3 spheroids as a 3-dimensional hypoxia model, in which the internal hypoxic region contained CSC-like cells expressing Oct4. The internal hypoxic region, which contained Oct4 expressing cells, disappeared following TX-402 treatment. In conclusion, hypoxia promoted the expansion of CSCs expressing CD133 and CD44 accompanied by an increase of stem cell factors. Its inhibition of hypoxia-induced CSC expansion makes TX-402 promising agent usable in combination for ovarian cancer therapy. PMID:25619133

  16. Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation

    PubMed Central

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

    2014-01-01

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

  17. EFFECTS OF INSECT HORMONE ACTIONS, 20E AND JH, ON MIDGUT STEM CELLS OF LEPIDOPTERA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Addition of the two principal insect hormones, 20-hydroxyecdysone (20E) and juvenile hormone (JH3) to the medium containing midgut stem cells cultured in vitro, induced stimulation of stem cell proliferation in a concentration-dependent manner. Stem cells were obtained from larvae of an economically...

  18. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells

    PubMed Central

    Seoane, Samuel; Bermúdez, María A.; Lamelas, Maria Luz; Garcia-Caballero, Tomás; Schneider, José; Perez-Fernandez, Roman; Vizoso, Francisco J.

    2014-01-01

    Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy. PMID:25296979

  19. Embryonic Stem Cells Cell Signalling Course

    E-print Network

    South Bohemia, University of

    Embryonic Stem Cells Cell Signalling Course Ceské Budjovice January 2013 #12;Pluripotent (stem(s) of differentiation ·Symmetric/asymmetric division ? ? ? ? #12;Where can we find the origins of stem cell research;1981 Lines of pluripotent cells were established for the first time from mouse embryo ­ Embryonic Stem Cells

  20. Embryonic Stem Cells Cell Signalling Course

    E-print Network

    South Bohemia, University of

    Embryonic Stem Cells Cell Signalling Course Ceské Budjovice November 2013 #12;Pluripotent (stem(s) of differentiation ·Symmetric/asymmetric division ? ? ? ? #12;Where can we find the origins of stem cell research;1981 Lines of pluripotent cells were established for the first time from mouse embryo ­ Embryonic Stem Cells

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

    PubMed

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

    2014-02-01

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

  2. Stem Cell Niche

    Microsoft Academic Search

    Pei Wen; Pei Sun; Rongwen Xi

    \\u000a The adult stem cells are essential for maintaining tissue homeostasis and commonly reside in specific local microenvironment\\u000a named niche. The niche keeps stem cells in multipotent state, prevents them from precocious differentiation and positions\\u000a them to undergo asymmetric division to produce differentiated ­progenies for tissue regeneration. The niches employ a variety\\u000a of factors including cell adhesion molecules, extra cellular matrix,

  3. Intestinal stem cells.

    PubMed

    Umar, Shahid

    2010-10-01

    Self-renewal in the intestinal epithelia is fueled by a population of undifferentiated intestinal stem cells (ISCs) that give rise to daughter or progenitor cells, which can subsequently differentiate into the mature cell types required for normal gut function. The cellular signals that regulate self-renewal are poorly understood and the factors that mediate the transition from a stem cell to a progenitor cell in the gut are unknown. Recent studies have suggested that ISCs are located either at the crypt base interspersed between the Paneth cells (eg, Lgr-5+ve cells) or at or near position 4 within the intestinal crypt (eg, DCAMKL-1 or Bmi-1+ve cells). This raises the possibility that distinct stem cell regions exist in the crypts and that ISC's state of activation will determine how the self-renewal is regulated in the intestinal tract. PMID:20683682

  4. The effect of mesenchymal stem cell conditioned media on corneal stromal fibroblast wound healing activities

    Microsoft Academic Search

    S. L. Watson; H. Marcal; M. Sarris; N. Di Girolamo; M. T. C. Coroneo; D. Wakefield

    2009-01-01

    AimsTo investigate the effects of conditioned media from mesenchymal stem cells (MSC) on the wound healing activities of corneal stromal fibroblasts.MethodsCell cycle analysis and early stage activation of apoptosis, chemotactic chambers and fibroblast-populated type I collagen gels were used to assess corneal stromal fibroblast proliferation, migration and contraction, respectively. Fibroblasts were obtained from human donor corneas and MSC from fresh

  5. Stem Cell Task Force

    NSDL National Science Digital Library

    This Web site from the National Institutes of Health (NIH) provides an overview of the activities of an NIH task force established to move the stem cell research agenda forward. The section titled Scientific Research may be of particular interest to researchers in this area. It provides links to the Web sites of stem cell-related research at a number of NIH institutes, as well as an extensive information index, a FAQs page about stem cell research, information on funding opportunities, and much more.

  6. Cardiac stem cell niches.

    PubMed

    Leri, Annarosa; Rota, Marcello; Hosoda, Toru; Goichberg, Polina; Anversa, Piero

    2014-11-01

    The critical role that stem cell niches have in cardiac homeostasis and myocardial repair following injury is the focus of this review. Cardiac niches represent specialized microdomains where the quiescent and activated state of resident stem cells is regulated. Alterations in niche function with aging and cardiac diseases result in abnormal sites of cardiomyogenesis and inadequate myocyte formation. The relevance of Notch1 signaling, gap-junction formation, HIF-1? and metabolic state in the regulation of stem cell growth and differentiation within the cardiac niches are discussed. PMID:25267073

  7. Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats.

    PubMed

    Mohamed, Rasha H; Karam, Rehab A; Hagrass, Hoda A; Amer, Mona G; Abd El-Haleem, Manal R

    2015-04-25

    The present study was designed to investigate whether spermatogonial stem cells (SSCs) have possible effect on doxorubicin (DOX)-induced testicular apoptosis and damaged oxidant/antioxidant balance in rats. Sixty male Albino rats were divided into 3 groups: the saline control group, the testicular toxicity group (2mg/kg DOX once a week for 8weeks) and the third group is a donor stem cells transplanted following pre-treatment with DOX. After the 8th week, the rats were sacrificed and tissues were collected and examined for CD95, CD95L, Caspase 3, and Caspase 8 gene expression using RT-PCR. While malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) were determined using colorimetric kits. Biochemical, histopathological and PCR results showed improvement of the SSCs' group compared to the DOX-group. It was observed that spermatogonial stem cell affected DOX-induced activation of intrinsic apoptotic signaling pathway via preventing DOX-induced increases in CD95 and CD95L levels as well as cleaved Caspase-8 and Caspase-3 levels in testicular tissues, however, spermatogonial stem cell decreased Dox-induced NF-?B activation as well. It can be concluded that SSCs may be utilized to develop new cell-based therapies, and to advance germline gene therapy. PMID:25680288

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

    PubMed Central

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

    2013-01-01

    Adult stem cells play an essential role in mammalian organ maintenance and repair throughout adulthood since they ensure that organs retain their ability to regenerate. The choice of cell fate by adult stem cells for cellular proliferation, self-renewal, and differentiation into multiple lineages is critically important for the homeostasis and biological function of individual organs. Responses of stem cells to stress, injury, or environmental change are precisely regulated by intercellular and intracellular signaling networks, and these molecular events cooperatively define the ability of stem cell throughout life. Skeletal muscle tissue represents an abundant, accessible, and replenishable source of adult stem cells. Skeletal muscle contains myogenic satellite cells and muscle-derived stem cells that retain multipotent differentiation abilities. These stem cell populations have the capacity for long-term proliferation and high self-renewal. The molecular mechanisms associated with deficits in skeletal muscle and stem cell function have been extensively studied. Muscle-derived stem cells are an obvious, readily available cell resource that offers promise for cell-based therapy and various applications in the field of tissue engineering. This review describes the strategies commonly used to identify and functionally characterize adult stem cells, focusing especially on satellite cells, and discusses their potential applications. PMID:23818907

  9. Nasal ectomesenchymal stem cells: Multi-lineage differentiation and transformation effects on fibrin gels.

    PubMed

    Zhang, Zhijian; He, Qinghua; Deng, Wenwen; Chen, Qian; Hu, Xinyuan; Gong, Aihua; Cao, Xia; Yu, Jiangnan; Xu, Ximing

    2015-05-01

    Ectomesenchymal stem cells (EMSCs) are novel adult stem cells derived from the cranial neural crest. However, their stemness and multi-lineage differentiation potential on three-dimensional fibrin gels has not yet been explored. The objective of this study was to investigate induced differentiation of EMSCs on fibrin gels and their remodeling effects on the scaffolds during the induced differentiation process. The results indicated that CD133(+)/nestin(+)/CD44(+) EMSCs were extensively distributed in the lamina propria of the nasal mucosa. The passaged cells could be induced to differentiate to a greater degree into neurons, Schwann cells and osteoblasts on three-dimensional fibrin gels than on two-dimensional glass slides. More importantly, the induced Schwann cells and osteoblasts exerted channelized and calcified remodeling effects, respectively, on the fibrin gels. Thus, these reshaped scaffolds have desirable biological properties, such as good cell adhesion, biocompatibility and guidance over the cell behavior, providing a tissue-committed niche for specific tissue generation. PMID:25725555

  10. SMOOTH MUSCLE STEM CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

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

    PubMed

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

    2014-01-01

    Adult neurogenesis occurs within the special microenvironment in the subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle of the mammalian brain. The special microenvironment is known as neurogenic niches. Multiple cell types, including endothelial cells, astroglia, ependymal cells, immature progeny of neural stem cells, and mature neurons, comprise the neurogenic niche. Differentiation of embryonic stem cells towards the neural lineage results in the generation of different neuronal subtypes and non-neuronal cells (mainly astrocytes). Therefore, it is reasonable to hypothesize that transplantation of human embryonic stem cell-derived neural progenitor cells can be used to modify neurogenic niches for facilitating adult neurogenesis. Furthermore, if generated new neurons are functionally integrated into the existing circuits of the aged hippocampus, synaptic plasticity in the hippocampus and learning/memory functions in aged mice should be enhanced. In this article, we provide a comprehensive review of the concepts in the regulation of adult neurogenesis by neurogenic niches and discuss the molecular mechanisms underlying the effect of stem cell transplantation on adult neurogenesis in aged hippocampus. PMID:24660111

  12. Clonal interrogation of stem cells

    Microsoft Academic Search

    Kristin Hope; Mickie Bhatia

    2011-01-01

    Individual stem cells are functionally defined by their self-renewal and differentiation potential. Methods for clonal analysis are essential for understanding stem cells, particularly given the increasing evidence for stem-cell heterogeneity. Stem cells reside within complex microenvironments, making single-cell analysis particularly challenging. Furthermore, simultaneous molecular and functional characterization of single stem cells is not trivial. Here we explore clonal assays applied

  13. LESSON PLAN Stem Cell Discussion

    E-print Network

    Rambaut, Andrew

    LESSON PLAN Stem Cell Discussion Learning objectives Students will: · consider the implications of stem cell research · research the current research situation · debate the future of stem cell of the Wellcome Trust, discusses why stem cells have the potential to treat many debilitating diseases, and why

  14. Information on Stem Cell Research

    MedlinePLUS

    Information on Stem Cell Research Research @ NINDS Stem Cell Highlights Submit a hESC line for NIH review (9/21/09) NIH Opens ... found here: Human Induced Pluripotent Stem Cells NINDS Stem Cell Research on Campus The Intramural Research Program of ...

  15. Interventions in Aging and Neurodegenerative Disease: Effects on Adult StemCells

    Microsoft Academic Search

    Adam D. Bachstetter; Carmellina Gemma; Paula C. Bickford

    Throughout the entire life span, stem cells are present in many organs of our body and continue to produce new cells which\\u000a are critical to maintain homeostasis and to repair damaged tissues. In the brain, stem cells generate new neurons through\\u000a a process called neurogenesis. With age, stem cells lose their ability to generate new cells, although the number of

  16. Microarrays and Stem Cells

    NSDL National Science Digital Library

    Mary Colvard

    2010-01-01

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

  17. The Effects of Topographical Patterns and Sizes on Neural Stem Cell Behavior

    PubMed Central

    Qi, Lin; Li, Ning; Huang, Rong; Song, Qin; Wang, Long; Zhang, Qi; Su, Ruigong; Kong, Tao; Tang, Mingliang; Cheng, Guosheng

    2013-01-01

    Engineered topographical manipulation, a paralleling approach with conventional biochemical cues, has recently attracted the growing interests in utilizations to control stem cell fate. In this study, effects of topological parameters, pattern and size are emphasized on the proliferation and differentiation of adult neural stem cells (ANSCs). We fabricate micro-scale topographical Si wafers with two different feature sizes. These topographical patterns present linear micro-pattern (LMP), circular micro-pattern (CMP) and dot micro-pattern (DMP). The results show that the three topography substrates are suitable for ANSC growth, while they all depress ANSC proliferation when compared to non-patterned substrates (control). Meanwhile, LMP and CMP with two feature sizes can both significantly enhance ANSC differentiation to neurons compared to control. The smaller the feature size is, the better upregulation applies to ANSC for the differentiated neurons. The underlying mechanisms of topography-enhanced neuronal differentiation are further revealed by directing suppression of mitogen-activated protein kinase/extracellular signaling-regulated kinase (MAPK/Erk) signaling pathway in ANSC using U0126, known to inhibit the activation of Erk. The statistical results suggest MAPK/Erk pathway is partially involved in topography-induced differentiation. These observations provide a better understanding on the different roles of topographical cues on stem cell behavior, especially on the selective differentiation, and facilitate to advance the field of stem cell therapy. PMID:23527077

  18. Cell Stem Cell The Systematic Production

    E-print Network

    Zandstra, Peter W.

    Cell Stem Cell Review The Systematic Production of Cells for Cell Therapies Daniel C. Kirouac1 10.1016/j.stem.2008.09.001 Stem cells have emerged as the starting material of choice. Translating the biological properties and potential of stem cells into therapies will require overcoming

  19. Colon cancer stem cells.

    PubMed

    Ricci-Vitiani, Lucia; Fabrizi, Eros; Palio, Elisabetta; De Maria, Ruggero

    2009-11-01

    Colorectal cancer (CRC) is the third most common form of cancer and the second cause of cancer-related death in the Western world, leading to 655,000 deaths worldwide per year (Jemal et al. in CA Cancer J Clin 56:106-130, 2006). Despite the emergence of new targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is increasingly supporting the idea that human cancers can be considered as a stem cell disease. According to the cancer stem cell model, malignancies originate from a small fraction of cancer cells that show self-renewal and pluripotency and are capable of initiating and sustaining tumor growth (Boman and Wicha in J Clin Oncol 26:2795-2799, 2008). The cancer-initiating cells or "cancer stem cells" were first identified in hematologic malignancies and most recently in several solid tumors, including CRC. The hypothesis of stem cell-driven tumorigenesis in colon cancer raises questions as to whether current treatments are able to efficiently target the tumorigenic cell population that is responsible for tumor growth and maintenance. This review will focus on the different aspects of stem cell biology in the context of CRC, which might help to understand the mechanisms that give rise to tumor development and resistance to therapy. First, we will briefly revise the knowledge available on normal intestinal stem cells and recent advances in understanding crypt biology, which have led to new theory on the origins of colon adenomas and cancers. Then, we will summarize the evidence and current status on colon cancer stem cells, focusing on their relevance and promises for the treatment of colorectal carcinoma. PMID:19727638

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

    Microsoft Academic Search

    Yasuyuki Amoh; Kensei Katsuoka; Robert M. Hoffman

    2010-01-01

    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

  1. Poly(ester-urethane) scaffolds: effect of structure on properties and osteogenic activity of stem cells.

    PubMed

    Kiziltay, Aysel; Marcos-Fernandez, Angel; San Roman, Julio; Sousa, Rui A; Reis, Rui L; Hasirci, Vasif; Hasirci, Nesrin

    2013-12-26

    The present study aimed to investigate the effect of structure (design and porosity) on the matrix stiffness and osteogenic activity of stem cells cultured on poly(ester-urethane) (PEU) scaffolds. Different three-dimensional (3D) forms of scaffold were prepared from lysine-based PEU using traditional salt-leaching and advanced bioplotting techniques. The resulting scaffolds were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), mercury porosimetry and mechanical testing. The scaffolds had various pore sizes with different designs, and all were thermally stable up to 300?°C. In vitro tests, carried out using rat bone marrow stem cells (BMSCs) for bone tissue engineering, demonstrated better viability and higher cell proliferation on bioplotted scaffolds compared to salt-leached ones, most probably due to their larger and interconnected pores and stiffer nature, as shown by higher compressive moduli, which were measured by compression testing. Similarly, SEM, von Kossa staining and EDX analyses indicated higher amounts of calcium deposition on bioplotted scaffolds during cell culture. It was concluded that the design with larger interconnected porosity and stiffness has an effect on the osteogenic activity of the stem cells. Copyright © 2013 John Wiley & Sons, Ltd. PMID:24376070

  2. Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival and proliferation and reduced scarring in skin wound healing.

    PubMed

    Lam, Mai T; Nauta, Allison; Meyer, Nathaniel P; Wu, Joseph C; Longaker, Michael T

    2013-03-01

    Wound healing is one of the most complex biological processes and occurs in all tissues and organs of the body. In humans, fibrotic tissue, or scar, hinders function and is aesthetically unappealing. Stem cell therapy offers a promising new technique for aiding in wound healing; however, current findings show that stem cells typically die and/or migrate from the wound site, greatly decreasing efficacy of the treatment. Here, we demonstrate effectiveness of a stem cell therapy for improving wound healing in the skin and reducing scarring by introducing stem cells using a natural patch material. Adipose-derived stromal cells were introduced to excisional wounds created in mice using a nonimmunogenic extracellular matrix (ECM) patch material derived from porcine small-intestine submucosa (SIS). The SIS served as an attractive delivery vehicle because of its natural ECM components, including its collagen fiber network, providing the stem cells with a familiar structure. Experimental groups consisted of wounds with stem cell-seeded patches removed at different time points after wounding to determine an optimal treatment protocol. Stem cells delivered alone to skin wounds did not survive post-transplantation as evidenced by bioluminescence in vivo imaging. In contrast, delivery with the patch enabled a significant increase in stem cell proliferation and survival. Wound healing rates were moderately improved by treatment with stem cells on the patch; however, areas of fibrosis, indicating scarring, were significantly reduced in wounds treated with the stem cells on the patch compared to untreated wounds. PMID:23072446

  3. Cell Stem Cell Short Article

    E-print Network

    Collins, James J.

    -renewal and reprogramming. INTRODUCTION The transcription factors OCT4, NANOG, and SOX2 are master regulators the requirement of OCT4, SOX2, and NANOG in stem cell function (De Los Angeles et al., 2012), discrepancies

  4. Effect of Dexamethasone, Insulin and EGF on the Myogenic Potential on Human Endometrial Stem Cell

    PubMed Central

    Jalali Tehrani, Hora; Parivar, Kazem; Ai, Jafar; Kajbafzadeh, Abdolmohammad; Rahbarghazi, Reza; Hashemi, Mehrdad; Sadeghizadeh, Majid

    2014-01-01

    Human endometrium contains mesenchymal stem cells (eMSC) which have the ability to differentiate into three cell lineages and the potential in therapeutic applications. We hypothesize that using environmental induction in culture media such as dexamethasone, human recombinant insulin and human epidermal growth factor (hEGF) can differentiate endometrial stem cells into myoblast. These agents have a broad range of effects in myoblast differentiation in-vitro. We used immunohystochemistry analysis and RT –PCR to evaluate the presence of skeletal muscle - specific proteins some of which are expressed in the early stage of differentiation including myoD and Desmin which expressed at later stages of differentiation. In conclusion eMSC can differentiate in culture media which contains above mentioned factors and use for therapeutic purpose in muscular degenerative disease. PMID:25237362

  5. Pleiotropic effects of cancer cells’ secreted factors on human stromal (mesenchymal) stem cells

    PubMed Central

    2013-01-01

    Introduction Studying cancer tumors’ microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor cells’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. Methods Morphological changes were assessed using fluorescence microscopy. Changes in gene expression were assessed using Agilent microarray and qRT-PCR. GeneSpring 12.1 and DAVID tools were used for bioinformatic and signaling pathway analyses. Cell migration was assessed using a transwell migration system. SB-431542, PF-573228 and PD98059 were used to inhibit transforming growth factor ? (TGF?), focal adhesion kinase (FAK), and mitogen activated protein kinase kinase (MAPKK) pathways, respectively. Interleukin-1? (IL1?) was measured using ELISA. Results MSCs exposed to secreted factors present in conditioned media (CM) from FaDu, MDA-MB-231, PC-3 and NCI-H522, but not from MCF7 and HT-29, developed an elongated, spindle-shaped morphology with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (approximately 80% to 99%, and 55% to 88% inhibition, respectively), while inhibition of the TGF? pathway was found to promote the pro-inflammatory response (approximately 3-fold increase). In addition, bioinformatics and pathway analysis of gene expression data from tumor cell lines combined with experimental validation revealed tumor-derived IL1? as one mediator of the pro-inflammatory phenotype observed in MSCs exposed to tumor CM. MSCs exhibited significant tropism toward secreted factors from the aforementioned tumor cell lines, while both normal and MSCs exposed to tumor CM were capable of attracting human peripheral blood mononuclear cells (PBMCs). Conclusions Our data revealed tumor-derived IL1? as one mediator of the pro-inflammatory response in MSCs exposed to tumor CM, which was found to be positively regulated by FAK and MAPK signaling and negatively regulated by TGF? signaling. Thus, our data support a model where MSCs could promote cancer progression through becoming pro-inflammatory cells within the cancer stroma. PMID:24405819

  6. Cell Stem Cell Alternative Induced Pluripotent

    E-print Network

    Zandstra, Peter W.

    Cell Stem Cell Letter Alternative Induced Pluripotent Stem Cell Characterization Criteria, Canada 4Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY 10029, USA 5Samuel.2009.02.010 ``Guidelines and Techniques for the Generation of Induced Pluripotent Stem Cells

  7. [Allogeneic hematopoietic stem cell transplantation].

    PubMed

    Mohty, Mohamad

    2008-12-15

    Allogeneic hematopoietic stem cell transplantation is a curative option in different hematologic malignancies. This benefit is traditionally based on the immune anti-tumour effect mediated by the allogeneic immune effectors derived from the graft, usually called "graft versus leukemia". Several categories of donors and sources of stem cells are currently used. In addition, different types of preparative regimens are available, and can be distinguished based on their myeloablative and immunosuppressive properties. Despite significant progress in terms of short term toxicity and morbidity, and despite effective prophylactic strategies, graft versus host disease remains a major complication, with its corollary of prolonged immunosuppression and opportunistic infections. However, allogeneic stem cell transplantation is rapidly expanding because the immunological anti-tumour effect has been demonstrated both in myeloid and lymphoid malignancies with a relatively acceptable risk of toxicity. PMID:19213539

  8. Effect of bone morphogenetic protein-4 (BMP4) on cardiomyocyte differentiation from mouse embryonic stem cell

    Microsoft Academic Search

    Masoumeh Fakhr Taha; Mojtaba Rezazadeh Valojerdi; Seyed Javad Mowla

    2007-01-01

    The present study was designed to evaluate the effect of BMP-4 on mouse embryonic stem cells (ESCs)-derived cardiomyocyte. Cardiac differentiation of the mouse ESCs was initiated by embryoid bodies (EBs) formation in hanging drops, transfer of EBs to the suspension culture and then plating onto gelatin-coated tissue culture plates. BMP-4 was added to culture medium throughout the suspension period. Cultures

  9. Neural stem cell transplantation in a model of fetal alcohol effects

    Microsoft Academic Search

    T. Yoshinaga; E. Hashimoto; W. Ukai; S. Toki; S. Saito; T. Saito

    Neural stem cell (NSC) transplantation has been investigated and developed in areas such as brain injury, stroke and neurodegenerative\\u000a diseases. Recently, emerging evidence suggest that many of clinical symptoms observed in psychiatric disease are likely related\\u000a to neural network disruptions including neurogenesis dysfunction. In the present study, we transplanted NSCs into a model\\u000a of fetal alcohol effects (FAE) for the

  10. Physiological effects of human muscle-derived stem cell implantation on urethral smooth muscle function

    Microsoft Academic Search

    Akira Furuta; Ron J. Jankowski; Ryan Pruchnic; Shin Egawa; Naoki Yoshimura; Michael B. Chancellor

    2008-01-01

    The physiological effects of human muscle-derived stem cell (MDSC) implantation on urethral smooth muscle function were investigated\\u000a in pudendal nerve-transected nude rats with human MDSC (TM) or saline (TS) injection into the proximal urethra compared with\\u000a sham-operated, saline-injected nude rats (SS). Leak point pressure (LPP) before and after hexamethonium application, which\\u000a can block autonomic efferent nerves, and proximal urethral contractile

  11. [An effective method for T-cell and B-cell simultaneous depletion in vitro from mobilized peripheral blood stem/progenitor cell graft for haploidentical transplantation].

    PubMed

    Xiao, Juan; Li, Hong-Hua; Jin, Xiang-Shu; Jin, Hai-Jie; Fu, Li-Ye; Gao, Chun-Ji; Han, Xiao-Ping; Yu, Li

    2008-10-01

    Depletion of T and B cells from the graft is prerequisite for haploidentical transplantation to decrease the risk of GVHD and EBV-associated lymphoproliferative disease. This study was aimed to investigate the performance of T-cell and B-cell simultaneous depletion from mobilized peripheral blood stem cells (PBSCs) for the first time in China, using anti-CD3 and anti-CD19 antibodies conjugated to magnetic microbeads by the CliniMACS device. The depletion efficiency of T-cell and B-cells was analyzed by flow cytometry; the function of the stem cells after depletion was evaluated using colony assays. The results indicated that the mononuclear cell count prior to T- and B-cell depletion was 4.88 x 10(10). After depletion, the percentage of T cells was 0.02% with a log (10) depletion of 4.4. The percentage of B cells was less than 0.01% with a log (10) depletion of at least 3.3. The product contained not only CD34(+) stem cells, but also NK cells, monocytes and granulocytes. After T- and B-cell depletion the purity of CD34(+) cells was 0.98%, the number of CD34 cells was 1.84 x 10(8) and their recovery rate was 69.7%. The number of NK cells was 2.54 x 10(9) and the recovery rate of NK cells was 71.7%. In vitro colony assays showed no negative impact on function of the hematopoietic stem cells. In conclusion, the CliniMACS system can be used to efficiently deplete T and B cells from PBSCs simultaneously, without adverse effect on biological function of hematopoietic stem cells. This study provides technical platform for haploidentical hematopoietic stem cell transplantation. PMID:18928610

  12. Stem Cell Research

    SciTech Connect

    Catherine Verfaillie

    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.

  13. The River of Stem Cells

    PubMed Central

    Chuong, Cheng-Ming; Widelitz, Randall Bruce

    2015-01-01

    In this issue of Cell Stem Cell, Greco et al. (2009) characterize the hair germ as a novel stop between bulge stem cell and transient amplifying cells during hair regeneration. The work implies stem cell states can be regulated to form different numbers of intermediate stops, depending on physiological requirements. PMID:19200797

  14. Stem Cells Branch Out

    NSDL National Science Digital Library

    Pamela Hines (AAAS; )

    2000-02-25

    Heals all manner of ailments, unlimited quantities, tailor-made for you. â?¦ No, it's not an advertisement for snake oil but may represent the promise of stem cellsâ??cells that have the potential to produce various cell types that make up the body and might therefore provide replacements for tissues damaged by age, trauma, or disease. But the work raises numerous questions as well: Can such promise be true? What is the ethical cost of such developments? Who will fund the necessary R&D? This article introduces a special issue on stem cells.

  15. Brain cancer stem cells

    Microsoft Academic Search

    Sara G. M. Piccirillo; Elena Binda; Roberta Fiocco; Angelo L. Vescovi; Khalid Shah

    2009-01-01

    Cancers comprise heterogeneous cells, ranging from highly proliferative immature precursors to more differentiated cell lineages.\\u000a In the last decade, several groups have demonstrated the existence of cancer stem cells in both nonsolid solid tumors, including\\u000a some of the brain: glioblastoma multiforme (GBM), medulloblastoma, and ependymoma. These cells, like their normal counterpart\\u000a in homologous tissues, are multipotent, undifferentiated, self-sustaining, yet transformed

  16. Cryoprotective Effect of Disaccharides on Cord Blood Stem Cells with Minimal Use of DMSO.

    PubMed

    Mantri, Santwana; Kanungo, Shyama; Mohapatra, P C

    2015-06-01

    Umbilical cord blood (UCB) is an extremely attractive source of stem cells for the treatment of various benign and malignant hematological and non-hematological disorders. To facilitate the preservation of these stem cells, 10 % dimethylsulfoxide (DMSO) is widely used as cryoprotectant in cord blood banks. But it is found to be toxic at this concentration with the result of serious side effects in recipients after infusion of DMSO-cryopreserved cells. Evaluation of viability and functionality of cryopreserved hematopoietic stem cells is needed with either inclusion of nontoxic additives alone or with reduced DMSO concentration. We assessed the post thawing viability of UCB stem cells in the freezing medium containing disaccharides (sucrose or trehalose) alone and in combination with reduced amount i.e. 2 % DMSO by trypan blue staining. The functionally active progenitor cells content of the optimized media was then evaluated and compared with 5% DMSO by a colony forming unit assay using methylcellulose based media. The freezing solution containing 0.2 M trehalose with 2 % DMSO came out to be superior in the evaluation of viability and generation of hematopoietic colonies of erythroid and myeloid lineage than 5 % DMSO alone. While the percentage of viability was lower than 2 % DMSO, as observed in the medium containing 0.2 M trehalose or sucrose alone, with poor outcome of generation of myeloid lineage based colonies. Our study results suggest that trehalose (0.2M) with the inclusion of reduced concentration of DMSO(2%) can better replace 5%DMSO rather than complete removal of DMSO from the freezing medium. PMID:25825559

  17. Immune effects of mesenchymal stem cells: Implications for Charcot–Marie–Tooth disease

    Microsoft Academic Search

    Alejandro Leal; Thomas E. Ichim; Annette M. Marleau; Fabian Lara; Shalesh Kaushal; Neil H. Riordan

    2008-01-01

    Mesenchymal stem cell (MSC) therapy is the most clinically advanced form of cell therapy, second to hematopoietic stem cell transplants. To date, MSC have been used for immune modulation in conditions such as Graft Versus Host Disease (GVHD) and Crohn’s Disease, for which Phase III clinical trials are currently in progress. Here, we review the immunological properties of MSC and

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

    SciTech Connect

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

    2005-08-12

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

  19. Effects of laser therapy on the proliferation of human periodontal ligament stem cells.

    PubMed

    Soares, Diego Moura; Ginani, Fernanda; Henriques, Águida Gomes; Barboza, Carlos Augusto Galvăo

    2015-04-01

    Low-level laser irradiation (LLLI) stimulates the proliferation of a variety of cell types. However, very little is known about the effect of laser therapy on dental stem cells. The aim of the present study was to evaluate the effect of LLLI (660 nm, 30 mW) on the proliferation rate of human periodontal ligament stem cells (hPDLSC), obtained from two healthy permanent third molars extracted due to surgical indication. Culture cells were either irradiated or not (control) with an InGaAIP diode laser at 0 and 48 h, using two different energy densities (0.5 J/cm˛, 16 s and 1.0 J/cm˛, 33 s). Cell proliferation was evaluated by the Trypan blue exclusion method and by measuring mitochondrial activity using the MTT-based cytotoxicity assay at intervals of 0, 24, 48, and 72 h after the first laser application. An energy density of 1.0 J/cm˛ improved the cell proliferation in comparison to the other groups (control and laser 0.5 J/cm˛) at 48 and 72 h. The group irradiated with 1.0 J/cm˛ presented significantly higher MTT activity at 48 and 72 h when compared to the energy density of 0.5 J/cm˛. It can be concluded that LLLI using infrared light and an energy density of 1.0 J/cm˛ has a positive stimulatory effect on the proliferation of hPDLSC. PMID:24013624

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

    PubMed

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

    2014-02-01

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

  1. 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 and GVHD are discussed. PMID:14633793

  2. Stem cells and the Planarian Schmidtea mediterranea

    Microsoft Academic Search

    Alejandro Sánchez Alvarado

    2007-01-01

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

  3. Cell Stem Cell Primed to Perish

    E-print Network

    Lahav, Galit

    Cell Stem Cell Previews Primed to Perish: Heightened Mitochondrial Priming Explains hESC Apoptosis Sensitivity Niels Geijsen1,2,* 1Hubrecht Institute for Developmental Biology and Stem Cell Research://dx.doi.org/10.1016/j.stem.2013.09.011 Human embryonic stem cells (hESCs) are hypersensitive to apoptotic stimuli

  4. Synergistic anti-proliferative effect of metformin and sorafenib on growth of anaplastic thyroid cancer cells and their stem cells.

    PubMed

    Chen, Guofang; Nicula, Diana; Renko, Kostja; Derwahl, Michael

    2015-04-01

    Sorafenib, a multikinase inhibitor has recently been approved for the treatment of radio-iodine refractory thyroid carcinoma. However, toxic side effects may lead to dose reduction. In the present study, we analyzed whether a combined therapy with metformin may allow a dose reduction of sorafenib without loss of effectiveness at the same time. In HTh74 anaplastic thyroid carcinoma (ATC) cells and its derived doxorubicin-resistant HTh74Rdox cell line, the growth inhibitory effect of sorafenib with or without metformin was investigated. Furthermore, an analysis of cell cycle arrest in response to sorafenib was performed and the ability of a combined treatment to induce apoptosis was analyzed. In addition, the effects on clonal growth and formation of stem cell-derived spheres were assayed. The influence of sorafenib and metformin on MAP kinase pathway was investigated by analysis of ERK phosphorylation. Sorafenib and metformin synergistically inhibited growth of the two thyroid cancer cell lines, with a more pronounced effect on the doxorubicin-resistant HTh74Rdox cell line. The two drugs also synergistically decreased sphere formation, which suggested a specific effect on thyroid cancer stem cells. The addition of metformin enabled a 25% dose reduction of sorafenib without loss of its growth inhibitory efficacy. Sorafenib and metformin synergistically decreased the proliferation of ATC cell lines and the outgrowth of their derived cancer stem cells. A combined treatment enabled a significant dose reduction of sorafenib. In respect to frequent toxic side effects, clinical studies in future should demonstrate whether the addition of metformin may be an advantage in the chemotherapy of patients with radio-iodine?resistant thyroid cancer. PMID:25683253

  5. The effect of recombinant mast cell growth factor on purified murine hematopoietic stem cells

    PubMed Central

    1991-01-01

    Pluripotent hematopoietic stem cells (PHSC) are very rare cells whose functional capabilities can only be analyzed indirectly. For a better understanding and possible manipulation of mechanisms that regulate self-renewal and commitment to differentiation of PHSC, it is necessary to purify these cells and to develop assays for their growth in vitro. In the present study, a rapid and simple, widely applicable procedure to highly purify day 14 spleen colony-forming cells (day 14 CFU-S) is described. Low density bone marrow cells (rho less than or equal to 1.078 g/cm3) were enriched by two successive light-activated cell sorting procedures. In the first sort, cells within a predetermined light scatter (blast cell) window that are wheat germ agglutinin/Texas Red (WGA/TxR) positive and mAb 15-1.4.1/fluorescein isothiocyanate negative (granulocyte-monocyte marker) were selected. In the second sort, cells were selected on the basis of retention of the supravital dye rhodamine 123 (Rh123). Cells that take up little Rh123 (Rh123 dull cells) and those that take up more Rh123 (Rh123 bright cells) were 237- fold and 132-fold enriched, respectively, for day 14 CFU-S. Both Rh123 fractions were cultured for various time periods in vitro in the presence of mast cell growth factor (MGF), with or without interleukin 3 (IL-3) or IL-1 alpha. Both Rh123 fractions proliferated in response to MGF alone as determined by a [3H]TdR assay or by counting nucleated cells present in the cultures over time. MGF also acted synergistically with both IL-3 and IL-1 alpha to promote stem cell proliferation. Stimulation of both Rh123 fractions with MGF alone did not result in a net increase of day 14 CFU-S. Stimulation with MGF + IL-3 or MGF + IL- alpha resulted in a 4.4- or 2.6-fold increase of day 14 CFU-S in the Rh123 dull fraction, and an 11.6-fold or 2.6-fold increase of day 14 CFU-S in the Rh123 bright fraction, respectively. The data presented in this paper indicate that in vitro MGF acts on primitive hematopoietic stem cells by itself and also is a potent synergistic factor in combination with IL-3 or IL-1 alpha. PMID:1708810

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

    PubMed

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

    2012-09-01

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

  7. Xenobiotic Effects on Intestinal Stem Cell Proliferation in Adult Honey Bee (Apis mellifera L) Workers

    PubMed Central

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

    2014-01-01

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

  8. 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). PMID:20373251

  9. Effects of Inflorescence Stem Structure and Cell Wall Components on the Mechanical Strength of Inflorescence Stem in Herbaceous Peony

    PubMed Central

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

    2012-01-01

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

  10. Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect

    PubMed Central

    Wang, Xingmin; Yang, Yonghong; Huycke, Mark M

    2015-01-01

    Objective Commensal bacteria and innate immunity play a major role in the development of colorectal cancer (CRC). We propose that selected commensals polarise colon macrophages to produce endogenous mutagens that initiate chromosomal instability (CIN), lead to expression of progenitor and tumour stem cell markers, and drive CRC through a bystander effect. Design Primary murine colon epithelial cells were repetitively exposed to Enterococcus faecalis-infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)—an endogenous mutagen and spindle poison produced by macrophages. CIN, gene expression, growth as allografts in immunodeficient mice were examined for clones and expression of markers confirmed using interleukin (IL) 10 knockout mice colonised by E. faecalis. Results Primary colon epithelial cells exposed to polarised macrophages or 4-hydroxy-2-nonenal developed CIN and were transformed after 10 weekly treatments. In immunodeficient mice, 8 of 25 transformed clones grew as poorly differentiated carcinomas with 3 tumours invading skin and/or muscle. All tumours stained for cytokeratins confirming their epithelial cell origin. Gene expression profiling of clones showed alterations in 3 to 7 cancer driver genes per clone. Clones also strongly expressed stem/progenitor cell markers Ly6A and Ly6E. Although not differentially expressed in clones, murine allografts positively stained for the tumour stem cell marker doublecortin-like kinase 1. Doublecortin-like kinase 1 and Ly6A/E were expressed by epithelial cells in colon biopsies for areas of inflamed and dysplastic tissue from E. faecalis-colonised IL-10 knockout mice. Conclusions These results validate a novel mechanism for CRC that involves endogenous CIN and cellular transformation arising through a microbiome-driven bystander effect. PMID:24906974

  11. Evaluation of Late Effects of Heavy-Ion Radiation on Mesenchymal Stem Cells

    NASA Technical Reports Server (NTRS)

    Gonda, S.R.; Behravesh, E.; Huff, J.L.; Johnson, F.

    2005-01-01

    The overall objective of this recently funded study is to utilize well-characterized model test systems to assess the impact of pluripotent stem cell differentiation on biological effects associated with high-energy charged particle radiation. These stem cells, specifically mesenchymal stem cells (MSCs), have the potential for differentiation into bone, cartilage, fat, tendons, and other tissue types. The characterization of the regulation mechanisms of MSC differentiation to the osteoblastic lineage by transcription factors, such as Runx2/Cbfa1 and Osterix, and osteoinductive proteins such as members of the bone morphogenic protein family are well established. More importantly, for late biological effects, MSCs have been shown to contribute to tissue restructuring and repair after tissue injury. The complex regulation of and interactions between inflammation and repair determine the eventual outcome of the responses to tissue injury, for which MSCs play a crucial role. Additionally, MSCs have been shown to respond to reactive oxygen species, a secondary effector of radiation, by differentiating. With this, we hypothesized that differentiation of MSCs can alter or exacerbate the damage initiated by radiation, which can ultimately lead to late biological effects of misrepair/fibrosis which may ultimately lead to carcinogenesis. Currently, studies are underway to examine high-energy X-ray radiation at low and high doses, approximately 20 and 200 Rad, respectively, on cytogenetic damage and gene modulation of isolated MSCs. These cells, positive for MSC surface markers, were obtained from three persons. In vitro cell samples were harvested during cellular proliferation and after both cellular recovery and differentiation. Future work will use established in vitro models of increasing complexity to examine the value of traditional 2D tissue-culture techniques, and utilize 3D in vitro tissue culture techniques that can better assess late effects associated with radiation.

  12. Stem Cells and Bioactive Materials

    Microsoft Academic Search

    Robert C. Bielby; Julia M. Polak

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

  13. Therapeutic effect of bone marrow mesenchymal stem cells on cold stress induced changes in the hippocampus of rats

    PubMed Central

    Kumar, Saravana Kumar Sampath; Perumal, Saraswathi; Rajagopalan, Vijayaraghavan

    2014-01-01

    The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mesenchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by flow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% confluence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress (cold stress), cold stress + PBS (intravenous infusion), and cold stress + bone marrow mesenchymal stem cells (1 × 106; intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacrificed for histological studies. Treatment with bone marrow mesenchymal stem cells significantly increased the number of neuronal cells in hippocampal CA1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions. PMID:25422634

  14. Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation.

    PubMed

    Kratchmarova, Irina; Blagoev, Blagoy; Haack-Sorensen, Mandana; Kassem, Moustapha; Mann, Matthias

    2005-06-01

    Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate. PMID:15933201

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

    PubMed Central

    Pacini, Nicola; Borziani, Fabio

    2014-01-01

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

  16. Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model.

    PubMed

    Serigano, Kenji; Sakai, Daisuke; Hiyama, Akihiko; Tamura, Futoshi; Tanaka, Masahiro; Mochida, Joji

    2010-10-01

    Transplantation of mesenchymal stem cells (MSCs) inhibits the progression of disc degeneration in animal models. We know of no study to determine the optimal number of cells to transplant into the degenerated intervertebral disc (IVD). To determine the optimal donor cell number for maximum benefit, we conducted an in vivo study using a canine disc degeneration model. Autologous MSCs were transplanted into degenerative discs at 10(5), 10(6), or 10(7)?cells per disc. The MSC-transplanted discs were evaluated for 12 weeks using plain radiography, magnetic resonance imaging, and gross and microscopic evaluation. Preservation of the disc height, annular structure was seen in MSC-transplantation groups compared to the operated control group with no MSC transplantation. Result of the number of remaining transplanted MSCs, the survival rate of NP cells, and apoptosis of NP cells in transplanted discs showed both structural microenvironment and abundant extracellular matrix maintained in 10(6) MSCs transplanted disc, while less viable cells were detected in 10(5) MSCs transplanted and more apoptotic cells in 10(7) MSCs transplanted discs. The results of this study demonstrate that the number of cells transplanted affects the regenerative capability of MSC transplants in experimentally induced degenerating canine discs. It is suggested that maintenance of extracellular matrix by its production from transplanted cells and/or resident cells is important for checking the progression of structural disruption that leads to disc degeneration. PMID:20839317

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-27

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

  19. Effect of stem cell activation, culture media of manipulated embryos, and site of embryo transfer in the production of F0 embryonic stem cell mice.

    PubMed

    Ramírez, Miguel Angel; Fernández-González, Raúl; Pérez-Crespo, Miriam; Pericuesta, Eva; Gutiérrez-Adán, Alfonso

    2009-06-01

    Recently, F0 embryonic stem (ES) cell mice have been produced by injection of ES cells into eight-cell embryos using either laser- or piezo-assisted injection systems. To simplify the injection procedure, we have optimized the conventional blastocyst injection method, free of laser- or piezo-assisted micromanipulation systems, to produce F0 ES cell pups. To increase the efficiency of producing mice from ES cell injection into eight-cell and blastocyst stage embryos, we have tested: 1) the effect of activating ES cell before injection, 2) the effect of in vitro culture in medium optimized for the survival of both ES cells and embryos, and 3) the effect of transferring the micromanipulated embryos into the oviduct versus into the uterus of CD1 foster mice. Two B6D2 hybrid ES cell lines were used for injection in a multifactorial analysis to evaluate the efficiency of producing live chimeric and F0 ES cell mice. Our results demonstrate that the activation of ES cells and the appropriate culture conditions are crucial parameters influencing the generation of F0 ES cell offspring. Transfer of blastocysts injected with ES cells into the oviduct of 0.5-day postcoitum pseudopregnant females increased the number of live animals with higher chimera proportion. Under these conditions, injections into eight-cell embryos produce a high number of F0 ES mice, and the conventional blastocyst injection method produces a lower number of F0 ES cell pups; however, the efficiency of production of chimeric mice with germline transmission was high. We have developed an economical and efficient technique for producing fully ES cell-derived F0 mice with full germline transmission that can be applied in many laboratories without the use of piezo or laser instruments. PMID:19228592

  20. Effects of low oxygen culture on pluripotent stem cell differentiation and teratoma formation

    E-print Network

    Millman, Jeffrey Robert

    2011-01-01

    Pluripotent stem cells (PSC) hold promise for the study of embryonic development and the treatment of many diseases. Most pluripotent cell research is performed in incubators with a gas-phase oxygen partial pressure (p02) ...

  1. Characterization of amniotic stem cells.

    PubMed

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

    2014-08-01

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

  2. [Multiple myeloma stem cell].

    PubMed

    Hosen, Naoki

    2015-01-01

    Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells. MM patients harbor phenotypic CD19+ B cells expressing the immunoglobulin gene sequence and the idiotype unique to the individual myeloma clone. However, in most MM patients CD19+ clonotypic B cells do not reconstitute MM disease upon transplantation into immune-deficient mice. In the SCID-rab and SCID-hu models, which enable engraftment of human MM in vivo, CD19-CD38++ plasma cells engrafted and rapidly propagated MM. These results indicate that MM-initiating cells are derived from plasma cells, which are terminally differentiated cells. It should be now clarified whether all MM plasma cells can exert as MM-initiating cells when located in the appropriate niche or only distinct myeloma stem cells can propagate MM. PMID:25626303

  3. Effects of encapsulated rabbit mesenchymal stem cells on ex vivo expansion of human umbilical cord blood hematopoietic stem/progenitor cells.

    PubMed

    Liu, Yang; Liu, Tianqing; Ma, Xuehu; Fan, Xiubo; Bao, Chunyu; Cui, Zhanfeng

    2009-03-01

    The expansion of umbilical cord blood mononuclear cells (UCB MNCs) was investigated in a novel co-culture system by means of encapsulation of rabbit bone marrow (BM) mesenchymal stem cells (MSCs) in alginate beads (Alg beads). Three kinds of media were applied and the experiments lasted for 7 days. The total nucleated cell density was measured every 24 h. Flow cytometric assay for CD34(+) cells and methylcellulose colony assays were carried out at 0, 72 and 168 h. It was found that the encapsulated MSCs illustrated remarkable effects on UCB MNCs expansion regardless of whether serum is present in culture media or not. At the end of 168 h co-culture, the total nucleated cell number was multiplied by 15 +/- 2.9 times, and CD34(+) cells 5.3 +/- 0.3 times and colony-forming units in culture (CFU-Cs) 5.6 +/- 1.2 times in the serum-free media supplemented with conventional dose of cytokines, which was very similar to the results in the containing 20% serum media. While in the control, i.e. MNC expansion without encapsulated MSCs, however, total nucleated cells density changed mildly, CD34(+) cells and CFU-Cs showed little effective expansion. It is demonstrated that the encapsulated stromal cells can support the expansion of UCB MNCs effectively under the experimental condition. PMID:18608809

  4. Biomaterials as Stem Cell Niche: Cardiovascular Stem Cells

    Microsoft Academic Search

    Ge Zhang; Laura J. Suggs

    \\u000a A tissue-specific stem cell niche functions to direct either self-renewal or differentiation. The niche comprises all local\\u000a cues that can be sensed by the cell including soluble and insoluble signals, physical forces and cell–cell contacts. Approximating\\u000a the stem cell niche through the utilization of biomaterials may give rise to a greater understanding of the biology of the\\u000a stem cell niche

  5. Embryonic Stem Cells

    NSDL National Science Digital Library

    Erdmann, Deanne

    2006-07-20

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

  6. 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

  7. The effect of the local delivery of alendronate on human adipose-derived stem cell-based bone regeneration

    Microsoft Academic Search

    Chau-Zen Wang; Shih-Mao Chen; Chung-Hwan Chen; Chih-Kuang Wang; Gwo-Jaw Wang; Je-Ken Chang; Mei-Ling Ho

    2010-01-01

    Recent studies have shown that alendronate (Aln) enhances the osteogenesis of osteoblasts and bone marrow mesenchymal stem cells. In this study, we hypothesize that Aln may act as an osteo-inductive factor to stimulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs) for bone regeneration. The in vitro effect of Aln (1–10 ?M) on the osteogenic ability of hADSCs was evaluated

  8. Once Upon a Stem Cell

    MedlinePLUS

    ... Science > Once Upon a Stem Cell Inside Life Science View All Articles | Inside Life Science Home Page Once Upon a Stem Cell By ... Do Geometry Sticky Stem Cells This Inside Life Science article also appears on LiveScience . Learn about related ...

  9. Embryonic Stem Cells from Parthenotes

    Microsoft Academic Search

    Jose B. Cibelli; Kerrianne Cunniff; Kent E. Vrana

    2006-01-01

    While human embryonic stem cells (hESCs) hold tremendous therapeutic potential, they also create societal and ethical dilemmas. Adult and placental stem cells represent two alternatives to the hESC, but may have technical limitations. An additional alternative is the stem cell derived from parthenogenesis. Parthenogenesis is a reproductive mechanism that is common in lower organisms and produces a live birth from

  10. Haute Culture: Tailoring stem cells

    E-print Network

    Chou, James

    research projects and its faculty have founded five stem cell-related startup companies and serveHaute Culture: Tailoring stem cells to make us well Tuesday, April 24, 2012 6:00-7:30 p;Haute Culture: Tailoring stem cells to make us well Moderator Brock Reeve, MPhil, MBA Executive Director

  11. Paracrine Effect of Mesenchymal Stem Cells Derived from Human Adipose Tissue in Bone Regeneration

    PubMed Central

    Linero, Itali; Chaparro, Orlando

    2014-01-01

    Mesenchymal stem cell (MSC) transplantation has proved to be a promising strategy in cell therapy and regenerative medicine. Although their mechanism of action is not completely clear, it has been suggested that their therapeutic activity may be mediated by a paracrine effect. The main goal of this study was to evaluate by radiographic, morphometric and histological analysis the ability of mesenchymal stem cells derived from human adipose tissue (Ad-MSC) and their conditioned medium (CM), to repair surgical bone lesions using an in vivo model (rabbit mandibles). The results demonstrated that both, Ad-MSC and CM, induce bone regeneration in surgically created lesions in rabbit's jaws, suggesting that Ad-MSC improve the process of bone regeneration mainly by releasing paracrine factors. The evidence of the paracrine effect of MSC on bone regeneration has a major impact on regenerative medicine, and the use of their CM can address some issues and difficulties related to cell transplants. In particular, CM can be easily stored and transported, and is easier to handle by medical personnel during clinical procedures. PMID:25198551

  12. Melanoma Stem Cells

    Microsoft Academic Search

    Tobias Schatton; Markus H. Frank

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

  13. Cancer Stem Cells

    Microsoft Academic Search

    Marcello Maugeri Saccŕ; Vito D’Andrea; Angelo Pulcini; Ruggero Maria

    \\u000a Far from being a new concept, the belief that cancer might originate from stem cells dates back to the mid-19th century when\\u000a Rudolf Virchow proposed that cancer arises from embryo-like cells, based on the histologic similarity between embryonic and\\u000a cancer tissues. This hypothesis was later extended by Cohnheim and Durante, who postulated that adult tissues contain embryonic\\u000a remnants that usually

  14. Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells on Mouse Bone-Marrow-Derived Dendritic Cells

    PubMed Central

    Ryu, Kyung-Ha

    2015-01-01

    Mesenchymal stem cells (MSCs) are considered valuable sources for cell therapy because of their immune regulatory function. Here, we investigated the effects of tonsil-derived MSCs (T-MSCs) on the differentiation, maturation, and function of dendritic cells (DCs). We examined the effect of T-MSCs on differentiation and maturation of bone-marrow- (BM-) derived monocytes into DCs and we found suppressive effect of T-MSCs on DCs via direct contact as well as soluble mediators. Moreover, T cell proliferation, normally increased in the presence of DCs, was inhibited by T-MSCs. Differentiation of CD4+ T cell subsets by the DC-T cell interaction also was inhibited by T-MSCs. The soluble mediators suppressed by T-MSCs were granulocyte-macrophage colony-stimulating factor (GM-CSF), RANTES, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Taken together, T-MSCs exert immune modulatory function via suppression of the differentiation, maturation, and function of BM-derived DCs. Our data suggests that T-MSCs could be used as a novel source of stem cell therapy as immune modulators. PMID:25784940

  15. Cell Stem Cell Sic Transit Gloria

    E-print Network

    Simons, Ben

    Cell Stem Cell Review Sic Transit Gloria: Farewell to the Epidermal Transit Amplifying Cell? Philip, Cambridge CB2 0RE, UK 4Wellcome Trust Centre for Stem Cell Research, Tennis Court Road, Cambridge CB2 1QR years, the prevailing model of epidermal homeostasis has been that epidermal stem cells give rise

  16. Effects of micropitted/nanotubular titania topographies on bone mesenchymal stem cell osteogenic differentiation.

    PubMed

    Zhao, Lingzhou; Liu, Li; Wu, Zhifen; Zhang, Yumei; Chu, Paul K

    2012-03-01

    Micro/nanotopographical modification of biomaterials constitutes a promising approach to direct stem cell osteogenic differentiation to promote osseointegration. In this work, titania nanotubes (NTs) 25 and 80 nm in size with the acid-etched Ti topography (AcidTi) and hierarchical hybrid micropitted/nanotubular topographies (Micro/5VNT and Micro/20VNT) are produced to mimic the structure of the natural bone extracellular matrix (ECM). The effects on bone mesenchymal stem cell (MSC) osteogenic differentiation are studied systematically by various microscopic and biological characterization techniques. Cell adhesion is assayed by nucleus fluorescence staining and cell proliferation is studied by CCK-8 assay and ?ow cytometry. Osteogenic differentiation is assayed by alkaline phosphatase (ALP) expression, collagen secretion, matrix mineralization, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis on the osteogenesis related gene expression. All the topographies are observed to induce MSC osteogenic differentiation in the absence of osteogenic supplements. The nanotube surfaces significantly promote cell attachment and spread, collagen secretion and ECM mineralization, as well as osteogenesis-related gene expression. Among them, Micro/20VNT shows the best ability to simultaneously promote MSC proliferation and osteogenic differentiation. Our results unambiguously demonstrate their excellent ability to support MSC proliferation and induce MSC osteogenic differentiation, especially those with the micropitted topography. PMID:22204980

  17. Stem cells: research tools and clinical treatments.

    PubMed

    Fahey, Michael C; Wallace, Euan M

    2011-09-01

    The term 'stem cell' most commonly refers to embryonic stem cells, particularly in the lay media; however, it also describes other cell types. A stem cell represents a cell of multi-lineage potential with the ability for self-renewal. It is now clear that the plasticity and immortality of a given stem cell will depend on what type of stem cell it is, whether an embryonic stem cell, a fetal-placental stem cell or an adult stem cell. Stem cells offer great promise as cell-based therapies for the future. With evolving technology, much of the socio-political debate regarding stem cells can now be avoided. PMID:21951457

  18. Selective JAK2/ABL dual inhibition therapy effectively eliminates TKI-insensitive CML stem/progenitor cells

    PubMed Central

    Lin, Hanyang; Chen, Min; Rothe, Katharina; Lorenzi, Matthew V.; Woolfson, Adrian; Jiang, Xiaoyan

    2014-01-01

    Imatinib Mesylate (IM) and other tyrosine kinase inhibitor (TKI) therapies have had a major impact on the treatment of chronic myeloid leukemia (CML). However, TKI monotherapy is not curative, with relapse and persistence of leukemic stem cells (LSCs) remaining a challenge. We have recently identified an AHI-1-BCR-ABL-JAK2 protein complex that contributes to the transforming activity of BCR-ABL and IM-resistance in CML stem/progenitor cells. JAK2 thus emerges as an attractive target for improved therapies, but off-target effects of newly developed JAK2 inhibitors on normal hematopoietic cells remain a concern. We have examined the biological effects of a highly selective, orally bioavailable JAK2 inhibitor, BMS-911543, in combination with TKIs on CD34+ treatment-naďve IM-nonresponder cells. Combination therapy reduces JAK2/STAT5 and CRKL activities, induces apoptosis, inhibits proliferation and colony growth, and eliminates CML LSCs in vitro. Importantly, BMS-911543 selectively targets CML stem/progenitor cells while sparing healthy stem/progenitor cells. Oral BMS-911543 combined with the potent TKI dasatinib more effectively eliminates infiltrated leukemic cells in hematopoietic tissues than TKI monotherapy and enhances survival of leukemic mice. Dual targeting BCR-ABL and JAK2 activities in CML stem/progenitor cells may consequently lead to more effective disease eradication, especially in patients at high risk of TKI resistance and disease progression. PMID:25226617

  19. Stem cells in gastric cancer

    PubMed Central

    Zhao, Yue; Feng, Fei; Zhou, Yong-Ning

    2015-01-01

    Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Cancer stem cells (CSCs), which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors, play important roles in cancer initiation, dissemination and recurrence. CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells. Several populations of multipotent gastric stem cells (GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair. These populations include the Villin+ and Lgr5+ GSCs in the antrum, the Troy+ chief cells in the corpus, and the Sox2+ GSCs that are found in both the antrum and the corpus. The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models. In addition to residing GSCs, bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection. Furthermore, expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines. Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models. In summary, the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients. PMID:25574084

  20. The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation

    PubMed Central

    Kang, So Mang; Lee, Kyoung Min

    2015-01-01

    Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases. PMID:25705693

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

    PubMed Central

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

    2013-01-01

    Objective: Osteoporosis or silent disease is a major bone disorder in elderly women in current century. Estrogen has an important role in osteogenesis and prevention of bone fractures. Hormone replacement therapy (HRT) is usually accompanied by such effects as breast and ovary cancers. Thus, there is an increasing demand for replacement with plant phytoestrogens. This study is focused on determining the effects of Foeniculum vulgare extract on proliferation and osteogenesis progress in human mesenchymal stem cells. Materials and Methods: Human mesenchymal stem cells were isolated and treated with different amount of plant extracts (0.5 to 100 µg/ml). Extract cytotoxicity was measured using MTT assay. The alkaline phosphatase enzyme activity was measured to evaluate the differentiation progress. Results: Results of MTT assay and alkaline phosphatase activity showed that Foeniculum vulgare extract, at range of 5 to 50 µg/ml, may positively affect cell proliferation and mineralization. The most proliferation and enzyme activity were seen with dose of 5 µg/ml. Conclusions: Foeniculum vulgare has been used in Iranian folk medicine for many years. Our in vitro study showed that Foeniculum vulgare extract has osteoprotective effects. PMID:25050267

  2. The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation.

    PubMed

    Song, Juhyun; Kang, So Mang; Lee, Kyoung Min; Lee, Jong Eun

    2015-01-01

    Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases. PMID:25705693

  3. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

    PubMed

    El-Merahbi, Rabih; Liu, Yen-Nien; Eid, Assaad; Daoud, Georges; Hosry, Leina; Monzer, Alissar; Mouhieddine, Tarek H; Hamade, Aline; Najjar, Fadia; Abou-Kheir, Wassim

    2014-01-01

    Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs. PMID:25380390

  4. Berberis libanotica Ehrenb Extract Shows Anti-Neoplastic Effects on Prostate Cancer Stem/Progenitor Cells

    PubMed Central

    Eid, Assaad; Daoud, Georges; Hosry, Leina; Monzer, Alissar; Mouhieddine, Tarek H.; Hamade, Aline; Najjar, Fadia; Abou-Kheir, Wassim

    2014-01-01

    Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs. PMID:25380390

  5. Comparison of the effects of human dental pulp stem cells and human bone marrow-derived mesenchymal stem cells on ischemic human astrocytes in vitro.

    PubMed

    Song, Miyeoun; Jue, Seong-Suk; Cho, Young-Ah; Kim, Eun-Cheol

    2015-06-01

    This study assesses the cytoprotective effects of human dental pulp stem cells (hDPSCs) and conditioned medium from hDPSCs (CM-hDPSCs) on ischemic human astrocytes (hAs) in vitro compared with human bone marrow-derived mesenchymal stem cells (hMSCs). Ischemia of hAs was induced by oxygen-glucose deprivation (OGD). CM-hDPSCs and hMSCs were collected after 48 hr of culture. Cell death was determined by 3-[4,5-dimethylthialzol-2-yl]-2,5-diphenyltetrazolium bromide and cellular ATP assays. The expression of glial fibrillary acidic protein (GFAP) and musashi-1 as markers of reactive astrogliosis was examined with immunochemical staining. mRNA expression and reactive oxygen species (ROS) were analyzed by RT-PCR and flow cytometry, respectively. OGD increased cytotoxicity in a time-dependent manner and decreased cellular ATP content concomitantly in hAs. Pretreatment and posttreatment with hDPSCs were associated with greater recovery from OGD-induced cytotoxicity in hAs compared with hMSCs. Similarly, CM-hDPSCs had a greater effect on OGD-induced cytotoxicity in a dose-dependent manner. Pre- and posttreatment with CM-hDPSCs or CM-hMSCs attenuated OGD-induced GFAP, nestin, and musashi-1 expression in hAs. Furthermore, treatment of cells with CM-hDPSCs and hMSCs blocked OGD-induced ROS production and interleukin-1ß upregulation. This study demonstrates for the first time that hDPSCs and CM-hDPSCs confer superior cytoprotection against cell death in an in vitro OGD model compared with hMSCs as shown by cell viability assay. Reactive gliosis, ROS production, and inflammatory mediators might contribute to this protective effect. Therefore, hDPSCs could represent an alternative source of cell therapy for ischemic stroke. © 2015 Wiley Periodicals, Inc. PMID:25663284

  6. Effects of Toll-Like Receptors 3 and 4 in the Osteogenesis of Stem Cells

    PubMed Central

    Qi, Chen; Xiaofeng, Xu; Xiaoguang, Wang

    2014-01-01

    Objective. To investigate the effects of Toll-like receptors in stem cell osteogenesis. Methods. Bone marrow mesenchymal stem cells (BMSCs) were divided into the blank group, the TLR-3 activated group, and the TLR-4 activated group. After 10 days' osteogenic-promoting culture, expression of type I collagen and osteocalcin was determined by Western blot. Osteoblasts (OBs) were also divided into three groups mentioned above. Alkaline phosphatase (ALP) and alizarin red staining were performed after 10 days' ossification-inducing culture. The expression of ?-catenin was investigated by Western blot. Results. Both the TLR-3 and TLR-4 activated groups had increased expression of type I collagen and osteocalcin; the effect of TLR-4 was stronger. The intensity of alizarin red and ALP staining was strongest in the TLR-3 activated group and weakest in the TLR-4 activated group. Activation of TLR-4 decreased the expression of ?-catenin, whilst activation of TLR-3 did not affect the expression of ?-catenin. Discussion. This study suggested that both TLR-3 and -4 promoted differentiation of BMSCs to OBs. TLR-3 had an inducing effect on the ossification of OBs to osteocytes, whilst the effect of TLR-4 was the opposite because of its inhibitory effect on the Wnt signaling pathway. PMID:25610471

  7. Stem Cell Plasticity, Beyond Alchemy

    Microsoft Academic Search

    Michael S. Rutenberg; Takashi Hamazaki; Amar M. Singh; Naohiro Terada

    2004-01-01

    Cell plasticity is a central issue in stem cell biology. Differentiated somatic nuclei have the flexibility to dedifferentiate\\u000a when transferred into oocytes or when fused to pluripotent embryonic stem cells. Recent publications also claim that somatic\\u000a stem cells can convert into developmentally unrelated cell types both in vivo and ex vivo without such drastic cell manipulations.\\u000a Some of these claims

  8. Perinatal sources of stem cells.

    PubMed

    Piskorska-Jasiulewicz, Magdalena Maria; Witkowska-Zimny, Ma?gorzata

    2015-01-01

    Recently, stem cell biology has become an interesting topic. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Successful application of hematopoietic stem cells in hematology has led to the search for other sources of stem cells and expanding the scale of their application. Perinatal stem cells are a versatile cell population, and they are interesting for both scientific and practical objectives. Stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in the case of genetic disorders. In this review paper we focus on the extraction and therapeutic potential of stem cells derived from perinatal tissues such as the placenta, the amnion, amniotic fluid, umbilical cord blood and Wharton's jelly. PMID:25748624

  9. Effects of different feeder layers on culture of bovine embryonic stem cell-like cells in vitro.

    PubMed

    Cong, Shan; Cao, Guifang; Liu, Dongjun

    2014-12-01

    To find a suitable feeder layer is important for successful culture conditions of bovine embryonic stem cell-like cells. In this study, expression of pluripotency-related genes OCT4, SOX2 and NANOG in bovine embryonic stem cell-like cells on mouse embryonic fibroblast feeder layers at 1-5 passages were monitored in order to identify the possible reason that bovine embryonic stem cell-like cells could not continue growth and passage. Here, we developed two novel feeder layers, mixed embryonic fibroblast feeder layers of mouse and bovine embryonic fibroblast at different ratios and sources including mouse fibroblast cell lines. The bovine embryonic stem cell-like cells generated in our study displayed typical stem cell morphology and expressed specific markers such as OCT4, stage-specific embryonic antigen 1 and 4, alkaline phosphatase, SOX2, and NANOG mRNA levels. When feeder layers and cell growth factors were removed, the bovine embryonic stem cell-like cells formed embryoid bodies in a suspension culture. Furthermore, we compared the expression of the pluripotent markers during bovine embryonic stem cell-like cell in culture on mixed embryonic fibroblast feeder layers, including mouse fibroblast cell lines feeder layers and mouse embryonic fibroblast feeder layers by real-time quantitative polymerase chain reaction. Results suggested that mixed embryonic fibroblast and sources including mouse fibroblast cell lines feeder layers were more suitable for long-term culture and growth of bovine embryonic stem cell-like cells than mouse embryonic fibroblast feeder layers. The findings may provide useful experimental data for the establishment of an appropriate culture system for bovine embryonic stem cell lines. PMID:24807816

  10. Salivary gland cancer stem cells.

    PubMed

    Adams, April; Warner, Kristy; Nör, Jacques E

    2013-09-01

    Emerging evidence suggests the existence of a tumorigenic population of cancer cells that demonstrate stem cell-like properties such as self-renewal and multipotency. These cells, termed cancer stem cells (CSC), are able to both initiate and maintain tumor formation and progression. Studies have shown that CSC are resistant to traditional chemotherapy treatments preventing complete eradication of the tumor cell population. Following treatment, CSC are able to re-initiate tumor growth leading to patient relapse. Salivary gland cancers are relatively rare but constitute a highly significant public health issue due to the lack of effective treatments. In particular, patients with mucoepidermoid carcinoma or adenoid cystic carcinoma, the two most common salivary malignancies, have low long-term survival rates due to the lack of response to current therapies. Considering the role of CSC in resistance to therapy in other tumor types, it is possible that this unique sub-population of cells is involved in resistance of salivary gland tumors to treatment. Characterization of CSC can lead to better understanding of the pathobiology of salivary gland malignancies as well as to the development of more effective therapies. Here, we make a brief overview of the state-of-the-science in salivary gland cancer, and discuss possible implications of the cancer stem cell hypothesis to the treatment of salivary gland malignancies. PMID:23810400

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

    PubMed

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

    2012-11-01

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

  12. Biological effects of T315I-mutated BCR-ABL in an embryonic stem cell-derived hematopoiesis model.

    PubMed

    Melkus, Michael; Bennaceur-Griscelli, Annelise; Valogne, Yannick; Flamant, Stephane; Chomel, Jean-Claude; Sorel, Nathalie; Bonnet, Marie-Laure; Deininger, Michael W; Mitjavila-Garcia, Maria-Teresa; Turhan, Ali G

    2013-04-01

    The occurrence of T315I mutation during the course of targeted therapies of chronic myeloid leukemia is a major concern because it confers resistance to all currently approved tyrosine kinase inhibitors. The exact phenotype of the hematopoietic stem cell and the hierarchical level of the occurrence of this mutation in leukemic hematopoiesis has not been determined. To study the effects of T315I-mutated breakpoint cluster region-abelson (BCR-ABL) in a primitive hematopoietic stem cell, we have used the murine embryonic stem cell (mESC)-derived hematopoiesis model. Native and T315I-mutated BCR-ABL were introduced retrovirally in mESC-derived embryonic bodies followed by induction of hematopoiesis. In several experiments, T315I-mutated and nonmutated BCR-ABL-transduced embryonic bodies rapidly generated hematopoietic cells on OP-9 feeders, with evidence of hematopoietic stem cell markers. After injection into NOD/SCID mice, these cells induced myeloid and lymphoid leukemias, whereas transplantation of control (nontransduced) hematopoietic cells failed to produce any hematopoietic reconstitution in vivo. Moreover, the expression of native and T315I-mutated BCR-ABL conferred to mESC-derived hematopoietic cells a self-renewal capacity demonstrated by the generation of leukemias after secondary transplantations. Secondary leukemias were more aggressive with evidence of extramedullary tumors. The expression of stem cell regulator Musashi-2 was found to be increased in bone marrow of leukemic mice. These data show that T315I-mutated BCR-ABL is functional at the stem cell level, conferring to mESC-derived leukemic cells a long-term hematopoietic repopulation ability. This model could be of interest to test the efficiency of drugs at the stem cell level in leukemias with T315I mutation. PMID:23287417

  13. An effective strategy of magnetic stem cell delivery for spinal cord injury therapy

    NASA Astrophysics Data System (ADS)

    Tukmachev, Dmitry; Lunov, Oleg; Zablotskii, Vitalii; Dejneka, Alexandr; Babic, Michal; Syková, Eva; Kubinová, Šárka

    2015-02-01

    Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal channel showed a good correlation with the calculated distribution of magnetic forces exerted onto the transplanted cells. The results suggest that focused targeting and fast delivery of stem cells can be achieved using the proposed non-invasive magnetic system. With future implementation the proposed targeting and delivery strategy bears advantages for the treatment of disease requiring fast stem cell transplantation.Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal channel showed a good correlation with the calculated distribution of magnetic forces exerted onto the transplanted cells. The results suggest that focused targeting and fast delivery of stem cells can be achieved using the proposed non-invasive magnetic system. With future implementation the proposed targeting and delivery strategy bears advantages for the treatment of disease requiring fast stem cell transplantation. Electronic supplementary information (ESI) available: Experimental procedures. See DOI: 10.1039/c4nr05791k

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

    Microsoft Academic Search

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

    2010-01-01

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

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

    PubMed

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

    2013-04-01

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

  16. Stem cell and precursor cell therapy

    Microsoft Academic Search

    Jingli Cai; Mahendra S. Rao

    2002-01-01

    Strategies for cell replacement therapy have been guided by the success in the hematopoietic stem cell field. In this review,\\u000a we discuss the basis of this success and examine whether this stem cell transplant model can be replicated in other systems\\u000a where stem cell therapy is being evaluated. We conclude that identifying the most primitive stem cell and using it

  17. Stem cells can form gap junctions with cardiac myocytes and exert pro-arrhythmic effects

    PubMed Central

    Smit, Nicoline W.; Coronel, Ruben

    2014-01-01

    Stem cell therapy has been suggested to be a promising option for regeneration of injured myocardium, for example following a myocardial infarction. For clinical use cell-based therapies have to be safe and applicable and are aimed to renovate the architecture of the heart. Yet for functional and coordinated activity synchronized with the host myocardium stem cells have to be capable of forming electrical connections with resident cardiomyocytes. In this paper we discuss whether stem cells are capable of establishing functional electrotonic connections with cardiomyocytes and whether these may generate a risk for arrhythmias. Application of stem cells in the clinical setting with outcomes concerning arrhythmogenic safety and future perspectives will also briefly be touched upon. PMID:25400586

  18. Effects of capsaicin on adipogenic differentiation in bovine bone marrow mesenchymal stem cell.

    PubMed

    Jeong, Jin Young; Suresh, Sekar; Park, Mi Na; Jang, Mi; Park, Sungkwon; Gobianand, Kuppannan; You, Seungkwon; Yeon, Sung-Heom; Lee, Hyun-Jeong

    2014-12-01

    Capsaicin is a major constituent of hot chili peppers that influences lipid metabolism in animals. In this study, we explored the effects of capsaicin on adipogenic differentiation of bovine bone marrow mesenchymal stem cells (BMSCs) in a dose- and time-dependent manner. The BMSCs were treated with various concentrations of capsaicin (0, 0.1, 1, 5, and 10 ?M) for 2, 4, and 6 days. Capsaicin suppressed fat deposition significantly during adipogenic differentiation. Peroxisome proliferator-activated receptor gamma, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer binding protein alpha, fatty acid binding protein 4, and stearoyl-CoA desaturase expression decreased after capsaicin treatment. We showed that the number of apoptotic cells increased in dose- and time-dependent manners. Furthermore, we found that capsaicin increased the expression levels of apoptotic genes, such as B-cell lymphoma 2-associated X protein and caspase 3. Overall, capsaicin inhibits fat deposition by triggering apoptosis. PMID:25358373

  19. Effects of Capsaicin on Adipogenic Differentiation in Bovine Bone Marrow Mesenchymal Stem Cell

    PubMed Central

    Jeong, Jin Young; Suresh, Sekar; Park, Mi Na; Jang, Mi; Park, Sungkwon; Gobianand, Kuppannan; You, Seungkwon; Yeon, Sung-Heom; Lee, Hyun-Jeong

    2014-01-01

    Capsaicin is a major constituent of hot chili peppers that influences lipid metabolism in animals. In this study, we explored the effects of capsaicin on adipogenic differentiation of bovine bone marrow mesenchymal stem cells (BMSCs) in a dose- and time-dependent manner. The BMSCs were treated with various concentrations of capsaicin (0, 0.1, 1, 5, and 10 ?M) for 2, 4, and 6 days. Capsaicin suppressed fat deposition significantly during adipogenic differentiation. Peroxisome proliferator-activated receptor gamma, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer binding protein alpha, fatty acid binding protein 4, and stearoyl-CoA desaturase expression decreased after capsaicin treatment. We showed that the number of apoptotic cells increased in dose- and time-dependent manners. Furthermore, we found that capsaicin increased the expression levels of apoptotic genes, such as B-cell lymphoma 2-associated X protein and caspase 3. Overall, capsaicin inhibits fat deposition by triggering apoptosis. PMID:25358373

  20. Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy: neuroprotective effects of combined therapy

    PubMed Central

    Wang, Lin; Jiang, Feng; Li, Qifeng; He, Xiaoguang; Ma, Jie

    2014-01-01

    Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27–28°C) can increase the survival rate of neural stem cells (1.0 × 105/?L) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hypothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and anti-apoptotic mechanisms. PMID:25422635

  1. Effect of Mesenchymal Stem Cells and a Novel Curcumin Derivative on Notch1 Signaling in Hepatoma Cell Line

    PubMed Central

    Abdel Aziz, Mohamed Talaat; Khaled, Hussien Mostafa; El Hindawi, Ali; Roshdy, Nagwa Kamal; Rashed, Laila A.; Hassouna, Amira A.; Taha, Fatma; Ali, Walaa Ibrahim

    2013-01-01

    This study was conducted to evaluate the effect of mesenchymal stem cells (MSCs) and a novel curcumin derivative (NCD) on HepG2 cells (hepatoma cell line) and to investigate their effect on Notch1 signaling pathway target genes. HepG2 cells were divided into HepG2 control group, HepG2 cells treated with MSC conditioned medium (MSCs CM), HepG2 cells treated with a NCD, HepG2 cells treated with MSCs CM and NCD, and HepG2 cells treated with MSCs CM (CM of MSCs pretreated with a NCD). Expression of Notch1, Hes1, VEGF, and cyclin D1 was assessed by real-time, reverse transcription-polymerase chain reaction (RT-PCR) in HepG2 cells. In addition, HepG2 proliferation assay was performed in all groups. Notch1 and its target genes (Hes1 and cyclin D1) were downregulated in all treated groups with more suppressive effect in the groups treated with both MSCs and NCD. Also, treated HepG2 cells showed significant decrease in cell proliferation rate. These data suggest that modulation of Notch1 signaling pathway by MSCs and/or NCD can be considered as a therapeutic target in HCC. PMID:24024180

  2. The effect of rabbit antithymocyte globulin on human mesenchymal stem cells.

    PubMed

    Franquesa, Marcella; Baan, Carla C; Korevaar, Sander S; Engela, Anja U; Roemeling-van Rhijn, Marieke; Weimar, Willem; Betjes, Michiel G H; Grinyo, Josep M; Hoogduijn, Martin J

    2013-06-01

    Mesenchymal stem cells (MSCs) possess immunomodulatory properties which are of key interest for their application in autoimmunity and transplantation. In transplantation, administration of MSCs has shown promising results in preclinical models and has recently moved to clinical trials. Therefore, it is important to study the interactions between MSCs and immunosuppressive drugs currently used in transplantation. We aimed to analyze the effect of rabbit antithymocyte globulin (rATG) MSCs. MSCs were obtained from perirenal fat of kidney donors and exposed to ranging doses of rATG (Thymoglobulin(®) , Genzyme; 0.5-100 ?g/ml). Binding of rATG, effects on viability and susceptibility to be killed by cytotoxic lymphocytes as well as effects on their immunosuppressive potential of MSCs were tested. rATG binds dose-dependently to MSCs. This binding was associated with slightly impaired viability after 48 and 72 h when compared with nonexposed MSCs. In contrast to nontreated MSCs, rATG preexposed MSCs were susceptible to be lysed by cytokine-activated CD8(+) cytotoxic cells and NKT cells. The capacity of MSCs to suppress the proliferation of anti-CD3/CD28 activated CD4 and CD8 T cells were reduced by the presence of rATG in the culture. rATG reduces the viability and antiproliferative capacity of MSCs in a dose-dependent manner and converts them into targets for CD8 T cells and NKT cell lysis. PMID:23682671

  3. Effect of aged bone marrow microenvironment on mesenchymal stem cell migration.

    PubMed

    Yang, Yan-Mei; Li, Ping; Cui, Dian-Chao; Dang, Rui-Jie; Zhang, Lei; Wen, Ning; Jiang, Xiao-Xia

    2015-04-01

    Mesenchymal stem cells (MSCs) are known to have many notable features, especially their multiple differentiation ability and immunoregulatory capacity. MSCs are important stem cells in the bone marrow (BM), and their characteristics are affected by the BM microenvironment. However, effects of the BM microenvironment on the properties of MSCs are not well understood. In this study, we found that BM from aged mice decreased MSC colony formation. Flow cytometry data showed that the proportion of B220(+) cells in BM from aged mice was significantly lower than that in BM from young mice, while the proportion of CD11b(+), CD3(+), Gr-1(+), or F4/80(+) cells are on the contrary. CD11b(+), B220(+), and Ter119(+) cells from aged mice were not the subsets that decreased MSC colony formation. We further demonstrated that both BM from aged mice and young mice exhibited similar effects on the proliferation of murine MSC cell line C3H10T1/2. However, when cocultured with BM from aged mice, C3H10T1/2 showed slower migration ability. In addition, we found that phosphorylation of JNK (c-Jun N-terminal kinases) in C3H10T1/2 cocultured with BM from aged mice was lower than that in C3H10T1/2 cocultured with BM from young mice. Collectively, our data revealed that BM from aged mice could decrease the migration of MSCs from their niche through regulating the JNK pathway. PMID:25693923

  4. The effect of Kisspeptin-10 on mesenchymal stem cells migration in vitro and in vivo

    PubMed Central

    Golzar, Fatemeh; Javanmard, Shaghayegh Haghjooy; Bahrambeigi, Vahid; Rafiee, Laleh

    2015-01-01

    Background: Kisspeptins (kp) activate a receptor coupled to a G?q subunit (GPR54 or KiSS-1R) receptor to perform a variety of functions, including inhibition of cell motility, chemotaxis, and metastasis. In this study we have investigated whether kp-10, the most potent member of the kisspeptin family, can modulate CXCR4 (C-X-C chemokine receptor type 4) expression and mesenchymal stem cells (MSCs) migration that may influence the development of tumors. Materials and Methods: We compared the directional migration of MSCs treated with 10-100 or 500 nM kp-10 for 24 hours and no treated cells using an in vitro transmembrane migration assay. In addition, Chloromethylbenzamido Dialkylacarbocyanine (CM-Dil) labeled adipose-derived mesenchymal stem cells treated with 10-100 or 500 nM kp-10 and no treated cells were transfused via the tail vein to the melanoma tumor bearing C57BL/6 mice. After 24 hours, the mice were scarified, the tumors were dissected, and the tumor cell suspensions were analyzed by flow cytometry for detection of CM-Dil+ MSCs. Results: We have found that kp-10 increased the MSCs migration at 100 nM, while it decreased the MSCs migration at 500 nM, both in vitro and in vivo, with a significant increase of CXCR4 expression at 100 nM kp-10 compared to the no treated cells, but it had no significant difference between the various concentrations of kp-10. Conclusion: Thus, our data showed that kp-10 can differently affect MSCs migration in various concentrations, probably through different effects on CXCR4 expression in various concentrations. PMID:25709985

  5. ``Stemness'': Transcriptional Profiling of Embryonic and Adult Stem Cells

    Microsoft Academic Search

    Miguel Ramalho-Santos; Soonsang Yoon; Yumi Matsuzaki; Richard C. Mulligan; Douglas A. Melton

    2002-01-01

    The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells. A total of 216 genes are enriched in all three types of stem cells, and several of these genes are clustered in the genome. When compared to differentiated cell types, stem cells express a significantly higher number of genes

  6. Hepatic differentiation capability of rat bone marrow-derived mesenchymal stem cells and hematopoietic stem cells

    Microsoft Academic Search

    Sai-Nan Shu; Lai Wei; Jiang-Hua Wang; Yu-Tao Zhan; Hong-Song Chen; Yu Wang

    2004-01-01

    AIM: To investigate the different effects of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) on hepatic differentiation. METHODS: MSCs from rat bone marrow were isolated and cultured by standard methods. HSCs from rat bone marrow were isolated and purified by magnetic activated cell sorting. Both cell subsets were induced. Morphology, RT-PCR and immunocytochemistry were used to identify the

  7. Stem cell transplantation in neurological diseases: improving effectiveness in animal models

    PubMed Central

    Adami, Raffaella; Scesa, Giuseppe; Bottai, Daniele

    2014-01-01

    Neurological diseases afflict a growing proportion of the human population. There are two reasons for this: first, the average age of the population (especially in the industrialized world) is increasing, and second, the diagnostic tools to detect these pathologies are now more sophisticated and can be used on a higher percentage of the population. In many cases, neurological disease has a pharmacological treatment which, as in the case of Alzheimer's disease, Parkinson's disease, Epilepsy, and Multiple Sclerosis can reduce the symptoms and slow down the course of the disease but cannot reverse its effects or heal the patient. In the last two decades the transplantation approach, by means of stem cells of different origin, has been suggested for the treatment of neurological diseases. The choice of slightly different animal models and the differences in methods of stem cell preparation make it difficult to compare the results of transplantation experiments. Moreover, the translation of these results into clinical trials with human subjects is difficult and has so far met with little success. This review seeks to discuss the reasons for these difficulties by considering the differences between human and animal cells (including isolation, handling and transplantation) and between the human disease model and the animal disease model. PMID:25364724

  8. Stem cell transplantation in neurological diseases: improving effectiveness in animal models.

    PubMed

    Adami, Raffaella; Scesa, Giuseppe; Bottai, Daniele

    2014-01-01

    Neurological diseases afflict a growing proportion of the human population. There are two reasons for this: first, the average age of the population (especially in the industrialized world) is increasing, and second, the diagnostic tools to detect these pathologies are now more sophisticated and can be used on a higher percentage of the population. In many cases, neurological disease has a pharmacological treatment which, as in the case of Alzheimer's disease, Parkinson's disease, Epilepsy, and Multiple Sclerosis can reduce the symptoms and slow down the course of the disease but cannot reverse its effects or heal the patient. In the last two decades the transplantation approach, by means of stem cells of different origin, has been suggested for the treatment of neurological diseases. The choice of slightly different animal models and the differences in methods of stem cell preparation make it difficult to compare the results of transplantation experiments. Moreover, the translation of these results into clinical trials with human subjects is difficult and has so far met with little success. This review seeks to discuss the reasons for these difficulties by considering the differences between human and animal cells (including isolation, handling and transplantation) and between the human disease model and the animal disease model. PMID:25364724

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

    PubMed Central

    2014-01-01

    Background Because there is little research on the effects of transplanted stem cells on neuronal metabolites in infarct areas, we transplanted human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into cerebral ischemic rabbits and examined the neuronal metabolites. Results Rabbits (n?=?40) were equally divided into sham, middle cerebral artery occlusion (MCAO), hUCB-MSC, and saline groups. The rabbit ischemic model was established by MCAO. The effects of hUCB-MSC transplantation were assessed by proton magnetic resonance spectroscopy (1H-MRS), neurological severity scores (NSSs), infarct area volume, neuronal density, and optical density (OD) of microtubule-associated protein 2 (MAP2)-positive cells. We also evaluated complete blood cell counts(CBCs) and serum biochemical parameters. NSSs in the hUCB-MSC group at 7 and 14 days after reperfusion were lower than in MCAO and saline groups (p?cells in the MCAO group were significantly lower than those in the sham group, whereas the neuronal density and OD of MAP2-positive cells in the hUCB-MSC group were higher than those in MCAO and saline groups (p?stem cells. No significant changes were observed in CBCs or serum biochemical parameters, suggesting that intravenous infusion of hUCB-MSCs is safe for rabbits in the short-term. PMID:24635873

  10. The effect of dimethyl sulfoxide on hepatic differentiation of mesenchymal stem cells.

    PubMed

    Alizadeh, Effat; Zarghami, Nosratollah; Eslaminejad, Mohamadreza Baghaban; Akbarzadeh, Abolfazl; Barzegar, Abolfazl; Mohammadi, Seyed Abolghasem

    2014-06-30

    Introduction: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are suitable choices in autologous stem cell treatment of liver-associated diseases due to their hepatic differentiation potential. Dimethyl sulfoxide (DMSO) is an amphipathic molecule with potential of delivering both lipophilic and hydrophilic agents into cells, also a common cryoprotectant for freezing of the cells. DMSO was used in some protocols for induction of AT-MSCs towards hepatocyte like cells. However, the effect of DMSO on hepatogenic differentiation of AT-MSCs were not surveyed, previously. In the present study, we aimed at evaluation of the effect of DMSO on differentiation of AT-MSCs into hepatic lineage. Methods: We isolated mesenchymal stem cells (MSCs) from adipose tissue, and then verifies multi-potency and surface markers of AT-MSCs . Isolated AT-MSCs randomly dispensed in four groups including Group 1: HGF treated, 2: HGF+ DMSO treated, 3: HGF+ DMSO+ OSM treated, and group control for a period of 3 weeks in the expansion medium without serum; EGF and bFGF were also included in the first days of inductions. The morphologic changes during induction period was observed with microscopy. The secretion of albumin (ALB) of the differentiating MSCs was investigated using ELISA, and urea production was evaluated using colorimetric assay. The qRT-PCR was performed for quantitation of hepatocyte marker genes including AFP, ALB, CK18, HNF4a, and HNF6. The glycogen storage of differentiated cells was visualized by periodic-acid Schiff's staining. Results: The results demonstrate that DMSO speeds up hepatic differentiation of AT-MSCs characterized by rapid changes in morphology; higher expression of hepatic marker gene (ALB) in both mRNA and protein level (P < 0.05); also increased transcriptional levels of other liver genes including CK18, HNF4a, and HNF6 (P < 0.01); and moreover, greater percentage of glycogen storage(p < 0.05) in DMSO-treated groups. Conclusion: DMSO catalyzes hepatic differentiation; therefore, using DMSO for acceleration of the hepatogenic protocols of AT-MSCs appears advantageous. PMID:24978442

  11. Amniotic fluid stem cells prevent ?-cell injury

    PubMed Central

    VILLANI, VALENTINA; MILANESI, ANNA; SEDRAKYAN, SARGIS; DA SACCO, STEFANO; ANGELOW, SUSANNE; CONCONI, MARIA TERESA; DI LIDDO, ROSA; DE FILIPPO, ROGER; PERIN, LAURA

    2015-01-01

    Background aims The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating ?-cell injury and restoring ?-cell function. Methods Streptozotocin-induced diabetic mice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation. Results AFSC injection resulted in protection from ?-cell damage and increased ?-cell regeneration in a subset of mice as indicated by glucose and insulin levels, increased islet mass and preservation of islet structure. Moreover, ?-cell preservation/regeneration correlated with activation of the insulin receptor/Pi3K/Akt signaling pathway and vascular endothelial growth factor-A expression involved in maintaining ?-cell mass and function. Conclusions Our results suggest a therapeutic role for AFSC in preserving and promoting endogenous ?-cell functionality and proliferation. The protective role of AFSC is evident when stem cell transplantation is performed before severe hyperglycemia occurs, which suggests the importance of early intervention. The present study demonstrates the possible benefits of the application of a non–genetically engineered stem cell population derived from amniotic fluid for the treatment of type 1 diabetes mellitus and gives new insight on the mechanism by which the beneficial effect is achieved. PMID:24210784

  12. Effects of BIO on proliferation and chondrogenic differentiation of mouse marrow-derived mesenchymal stem cells

    PubMed Central

    Baghaban Eslaminejad, Mohamadreza; Fallah, Nasrin

    2013-01-01

    In vitro expansion of mesenchymal stem cell (MSCs) into large number is necessary for their application in cell-based treatment of articular cartilage defects. On the other hand, some studies have indicated that BIO (6-Bromoindirubin-3-Oxime) possesses mitogenic effects on cell culture. The objective of the present study was to examine the effect of BIO on in vitro expansion and chondrogenic differentiation of mouse marrow-derived MSCs. The culture was established using bone marrow tissue obtained from 10 NMRI mice. MSC nature of the isolated cells was verified according to the minimal criteria proposed for MSC. Passaged-3 cells were seeded in 24-well culture plates and treated by 0.05, 0.01, 0.1, 1.0 and 1.5 µM BIO for seven days. The culture without BIO was taken as the control. At the end of cultivation period, the cultures were examined for viable cell number which was then used to calculate population doubling time (PDT). The BIO with higher proliferation-promoting effect was investigated for its chondrogenic effect on MSC culture. There was significantly more viable cells at the cultures treated by 0.1 µM BIO. At this culture the cells tended to double their population in rapid rate (each 43.07 hr) than the cells treated with the other BIO concentrations (p < 0.05). Interestingly treatment of MSC chondrogenic culture with 0.1 µM BIO led to the up-regulation of cartilage specific genes including aggrecan, collagen II and Sox9. In conclusion BIO at 0.1 µM could enhance mouse MSC in vitro proliferation as well as their chondrogenic differentiation. These findings would be of great importance for the field of regenerative medicine. PMID:25653775

  13. Stem cell senescence. Effects of REAC technology on telomerase-independent and telomerase-dependent pathways

    PubMed Central

    Rinaldi, S.; Maioli, M.; Pigliaru, G.; Castagna, A.; Santaniello, S.; Basoli, V.; Fontani, V.; Ventura, C.

    2014-01-01

    Decline in the gene expression of senescence repressor Bmi1, and telomerase, together with telomere shortening, underlay senescence of stem cells cultured for multiple passages. Here, we investigated whether the impairment of senescence preventing mechanisms can be efficiently counteracted by exposure of human adipose-derived stem cells to radio electric asymmetrically conveyed fields by an innovative technology, named Radio Electric Asymmetric Conveyer (REAC). Due to REAC exposure, the number of stem cells positively stained for senescence associated ?-galactosidase was significantly reduced along multiple culturing passages. After a 90-day culture, REAC-treated cells exhibited significantly higher transcription of Bmi1 and enhanced expression of other stem cell pluripotency genes and related proteins, compared to unexposed cells. Transcription of the catalytic telomerase subunit (TERT) was also increased in REAC-treated cells at all passages. Moreover, while telomere shortening occurred at early passages in both REAC-treated and untreated cells, a significant rescue of telomere length could be observed at late passages only in REAC-exposed cells. Thus, REAC-asymmetrically conveyed radio electric fields acted on a gene and protein expression program of both telomerase-independent and telomerase-dependent patterning to optimize stem cell ability to cope with senescence progression. PMID:25224681

  14. Effects of silver nanoparticles on human and rat embryonic neural stem cells

    PubMed Central

    Liu, Fang; Mahmood, Meena; Xu, Yang; Watanabe, Fumiya; Biris, Alexandru S.; Hansen, Deborah K.; Inselman, Amy; Casciano, Daniel; Patterson, Tucker A.; Paule, Merle G.; Slikker, William; Wang, Cheng

    2015-01-01

    Silver nano-particles (Ag-NPs) are becoming increasingly prevalent in consumer products as antibacterial agents. The increased use of Ag NP-enhanced products will almost certainly increase environmental silver levels, resulting in increased exposures and the potential for increased adverse reactions including neurotoxic effects. In the present study, embryonic neural stem cells (NSCs) from human and rat fetuses (gestational day-16) were used to determine whether Ag-NPs are capable of causing developmental neurotoxicity. The NSCs were cultured in serum free medium supplemented with appropriate growth factors. On the eighth day in vitro (DIV 8), the cells were exposed to Ag-NPs at concentrations of 1, 5, 10, and 20 ?g/ml for 24 h. The cultured cells then were characterized by NSC markers including nestin and SOX2 and a variety of assays were utilized to determine the effects of Ag-NPs on NSC proliferation and viability and the underlying mechanisms associated with these effects. The results indicate that mitochondrial viability (MTT metabolism) was substantially attenuated and LDH release was increased significantly in a dose-dependent manner. Ag-NPs-induced neurotoxicity was further confirmed by up-regulated Bax protein expression, an increased number of TUNEL-positively stained cells, and elevated reactive oxygen species (ROS). NSC proliferation was also significantly decreased by Ag-NPs. Co-administration of acetyl-L-carnitine, an antioxidant agent, effectively blocked the adverse effects associated with Ag-NP exposure.

  15. Cell Stem Cell Adult SVZ Stem Cells Lie in a Vascular

    E-print Network

    Lin, Gang

    Cell Stem Cell Article Adult SVZ Stem Cells Lie in a Vascular Niche: A Quantitative Analysis Susan K. Goderie,1 Badrinath Roysam,3 and Sally Temple1,2,* 1New York Neural Stem Cell Institute within stem cell niches. Here, we examine whether neural stem cells (NSCs) in the adult subventricular

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

    NASA Technical Reports Server (NTRS)

    Kigel, J.; Cosgrove, D. J.

    1991-01-01

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

  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. PMID:25388388

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

    SciTech Connect

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

    2012-02-15

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

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

    EPA Science Inventory

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

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

    PubMed Central

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

    2014-01-01

    Mesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-? would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN-? gene under the control of the EF1? promoter. The IFN-?-modified MSCs effectively secreted functional IFN-?, which led to long-term expression of TRAIL. More importantly, the IFN-?-modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN-?-modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN-?-modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN-?-modified MSCs. PMID:24971369

  1. Stem cells—meet immunity

    Microsoft Academic Search

    Tracy S. P. Heng; Jarrod A. Dudakov; Danika M. P. Khong; Ann P. Chidgey; Richard L. Boyd

    2009-01-01

    The ability of stem cells to differentiate into various different cell types holds great promise for the treatment of irreversible\\u000a tissue damage that occurs in many debilitating conditions. With stem cell research advancing at a tremendous pace, it is becoming\\u000a clear that one of the greatest hurdles to successful stem cell-derived therapies is overcoming immune rejection of the transplant.\\u000a Although

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

    PubMed

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

    2013-01-01

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

  3. Follicle stimulating hormone receptor in mesenchymal stem cells integrates effects of glycoprotein reproductive hormones.

    PubMed

    Tourkova, Irina L; Witt, Michelle R; Li, La; Larrouture, Quitterie; Liu, Li; Luo, Jianhua; Robinson, Lisa J; Blair, Harry C

    2015-01-01

    Previously we reported that follicle stimulating hormone (FSH) affects bone degradation in human cells and in follicle stimulating hormone receptor (FSH-R) null mice. Here we describe a FSH-R knockout bone-formation phenotype. We used mesenchymal stem cells (MSCs), osteoblast precursors that express FSH-R, to determine whether FSH regulates bone formation. FSH stimulates MSC cell adhesion 1-3 h and proliferation at 24 h after addition. On the basis of phylogenetic and clinical precedents, we also examined effects of pregnant levels of human chorionic gonadotropin (hCG) on MSCs. We found effects similar to those of FSH, and RNAi knockdown of FSH-R abrogated both FSH and hCG effects on MSCs. In contrast to effects on MSCs, neither FSH nor hCG had significant effects on osteoblast maturation. Also in MSCs, short-term treatment by FSH and hCG altered signaling pathways for proliferation, including Erk1/2 phosphorylation. Our results show augmentation of MSC proliferation by either FSH at menopausal levels or hCG at normal pregnant levels. We conclude that FSH-R participates in regulation of MSC precursor pools in response to either FSH or hCG, integrating the effects of these two glycoprotein hormones. PMID:25118101

  4. Antiproliferative and Apoptotic Effects of a Specific Antiprostate Stem Cell Single Chain Antibody on Human Prostate Cancer Cells

    PubMed Central

    Nejatollahi, Foroogh; Abdi, Soghra

    2013-01-01

    Prostate stem cell antigen (PSCA) is a highly glycosylated cell surface protein which is overexpressed in several malignancies including prostate, pancreas, and urinary bladder cancers. Tumor suppression has been reported by anti-PSCA antibody. Small and high affinity single chain antibodies (scFv) have been introduced as effective agents for cancer immunotargeting approaches. In the present study, we used a phage antibody display library of scFv and selected two antibodies against two immunodominant epitopes of PSCA by panning process. The reactivity of the scFvs for the corresponding epitopes was determined by phage ELISA. The binding specificity of antibodies to PSCA-expressing prostate cancer cell line, DU-145, was analyzed by flow cytometry. The antiproliferative and apoptotic induction effects were evaluated by MTT and Annexin-V assays, respectively. Results represented functional scFv C5-II which could bind specifically to DU-145 cells and significantly inhibited the proliferation of these cells (61%) with no effect on PSCA-negative cells. The antibody also induced apoptosis in the PSCA expressing cells. The percentage of the apoptotic cells after 24?hrs of exposure to 500?scFv/cell was 33.80%. These results demonstrate that the functional anti-PSCA scFv C5-II has the potential to be considered as a new agent for targeted therapy of prostate cancer. PMID:24391668

  5. Control of Stemness by Fibroblast Growth Factor Signaling in Stem Cells and Cancer Stem Cells

    Microsoft Academic Search

    Noriko Gotoh

    2009-01-01

    Since the discovery of stem cells, scientists have invested tremendous effort in establishing in vitro culture conditions in order to maintain the self-renewal and efficient proliferative capabilities of stem cells by manipulating a va- riety of growth factors. Fibroblast growth factor (FGF) is one of the most common growth factors used to expand stem cells, including human embryonic stem (hES)

  6. Effect of VEGF on the Regenerative Capacity of Muscle Stem Cells in Dystrophic Skeletal Muscle

    Microsoft Academic Search

    Bridget M Deasy; Joseph M Feduska; Thomas R Payne; Yong Li; Fabrisia Ambrosio; Johnny Huard

    2009-01-01

    We have isolated a population of muscle-derived stem cells (MDSCs) that, when compared with myoblasts, display an improved regeneration capacity, exhibit better cell survival, and improve myogenesis and angiogenesis. In addition, we and others have observed that the origin of the MDSCs may reside within the blood vessel walls (endothelial cells and pericytes). Here, we investigated the role of vascular

  7. Stem Cell-Based Therapies for Ischemic Stroke

    PubMed Central

    Hao, Lei; Zou, Zhongmin; Tian, Hong; Zhang, Yubo; Zhou, Huchuan; Liu, Lei

    2014-01-01

    In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs), inducible pluripotent stem cells (iPSCs), neural stem cells (NSCs), and mesenchymal stem cell (MSCs) might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future. PMID:24719869

  8. A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

    PubMed Central

    Yang, Ruili; Liu, Yi; Kelk, Peyman; Qu, Cunye; Akiyama, Kentaro; Chen, Chider; Atsuta, Ikiru; Chen, WanJun; Zhou, Yanheng; Shi, Songtao

    2013-01-01

    Bone marrow mesenchymal stem cells (MSCs) comprise a heterogeneous population of postnatal progenitor cells with profound immunomodulatory properties, such as upregulation of Foxp3+ regulatory T cells (Tregs) and downregulation of Th17 cells. However, it is unknown whether different MSC subpopulations possess the same range of immunomodulatory function. Here, we show that a subset of single colony-derived MSCs producing IL-17 is different from bulk MSC population in that it cannot upregulate Tregs, downregulate Th17 cells, or ameliorate disease phenotypes in a colitis mouse model. Mechanistically, we reveal that IL-17, produced by these MSCs, activates the NF?B pathway to downregulate TGF-? production in MSCs, resulting in abolishment of MSC-based immunomodulation. Furthermore, we show that NF?B is able to directly bind to TGF-? promoter region to regulate TGF-? expression in MSCs. Moreover, these IL-17+ MSCs possess anti-Candida albicans growth effects in vitro and therapeutic effect in C. albicans-infected mice. In summary, this study shows that MSCs contain an IL-17+ subset capable of inhibiting C. albicans growth, but attenuating MSC-based immunosuppression via NF?B-mediated downregulation of TGF-?. PMID:23266891

  9. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Jenq, Robert R.; Perales, Miguel-Angel; Littmann, Eric R.; Morjaria, Sejal; Ling, Lilan; No, Daniel; Gobourne, Asia; Viale, Agnes; Dahi, Parastoo B.; Ponce, Doris M.; Barker, Juliet N.; Giralt, Sergio; van den Brink, Marcel; Pamer, Eric G.

    2014-01-01

    Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT. PMID:24939656

  10. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation.

    PubMed

    Taur, Ying; Jenq, Robert R; Perales, Miguel-Angel; Littmann, Eric R; Morjaria, Sejal; Ling, Lilan; No, Daniel; Gobourne, Asia; Viale, Agnes; Dahi, Parastoo B; Ponce, Doris M; Barker, Juliet N; Giralt, Sergio; van den Brink, Marcel; Pamer, Eric G

    2014-08-14

    Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT. PMID:24939656

  11. Stem cells for myocardial regeneration.

    PubMed

    Orlic, Donald; Hill, Jonathan M; Arai, Andrew E

    2002-12-13

    Stem cells are being investigated for their potential use in regenerative medicine. A series of remarkable studies suggested that adult stem cells undergo novel patterns of development by a process referred to as transdifferentiation or plasticity. These observations fueled an exciting period of discovery and high expectations followed by controversy that emerged from data suggesting cell-cell fusion as an alternate interpretation for transdifferentiation. However, data supporting stem cell plasticity are extensive and cannot be easily dismissed. Myocardial regeneration is perhaps the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes are generated in what was previously considered a postmitotic organ. On the basis of postmortem microscopic analysis, it is proposed that renewal is achieved by stem cells that infiltrate normal and infarcted myocardium. To further understand the role of stem cells in regeneration, it is incumbent on us to develop instrumentation and technologies to monitor myocardial repair over time in large animal models. This may be achieved by tracking labeled stem cells as they migrate into myocardial infarctions. In addition, we must begin to identify the environmental cues that are needed for stem cell trafficking and we must define the genetic and cellular mechanisms that initiate transdifferentiation. Only then will we be able to regulate this process and begin to realize the full potential of stem cells in regenerative medicine. PMID:12480809

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

    PubMed Central

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

    2013-01-01

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

  13. Effect of Surface Patterning and Presence of Collagen I on the Phenotypic Changes of Embryonic Stem Cell Derived Cardiomyocytes

    E-print Network

    Wan, C. R.

    Embryonic stem cell derived cardiomyocytes have been widely investigated for stem cell therapy or in vitro model systems. This study examines how two specific biophysical stimuli, collagen I and cell alignment, affect the ...

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

    SciTech Connect

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

    1996-06-01

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

  15. Stem cells and neurodegenerative diseases

    Microsoft Academic Search

    LingLing Hou; Tao Hong

    2008-01-01

    Neurodegenerative diseases are characterized by the neurodegenerative changes or apoptosis of neurons involved in networks,\\u000a which are important to specific physiological functions. With the development of old-aging society, the incidence of neurodegenerative\\u000a diseases is on the increase. However, it is difficult to diagnose for most of neurodegenerative diseases. At present, there\\u000a are too few effective therapies. Advances in stem cell

  16. DEVELOPMENTAL BIOLOGY: Orienting Stem Cells

    NSDL National Science Digital Library

    Matthew R. Wallenfang (University of Pennsylvania; Department of Cell and Developmental Biology)

    2003-09-12

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

  17. The therapeutic effects of human adipose-derived stem cells in Alzheimer's disease mouse models.

    PubMed

    Chang, Keun-A; Kim, Hee Jin; Joo, Yuyoung; Ha, Sungji; Suh, Yoo-Hun

    2014-01-01

    Alzheimer's disease (AD) is an irreversible neurodegenerative disease, still lacking proper clinical treatment. Therefore, many researchers have focused on the possibility of therapeutic use of stem cells for AD. Adipose-derived stem cells (ASCs), mesenchymal stem cells (MSCs) isolated from adipose tissue, are well known for their pluripotency and their ability to differentiate into multiple tissue types and have immune modulatory properties similar to those of MSCs from other origins. Because of their biological properties, ASCs can be considered for cell therapy and neuroregeneration. Our recent results clearly showed the therapeutic potential of these cells after transplantation into Tg2576 mice (an AD mouse model). Intravenously or intracerebrally transplanted human ASCs (hASCs) greatly improved the memory impairment and the neuropathology, suggesting that hASCs have a high therapeutic potential for AD. PMID:24157626

  18. Indirect Effects of Wnt3a/?-Catenin Signalling Support Mouse Spermatogonial Stem Cells In Vitro

    PubMed Central

    Yeh, Jonathan R.; Zhang, Xiangfan; Nagano, Makoto C.

    2012-01-01

    Proper regulation of spermatogonial stem cells (SSCs) is crucial for sustaining steady-state spermatogenesis. Previous work has identified several paracrine factors involved in this regulation, in particular, glial cell line-derived neurotrophic factor and fibroblast growth factor 2, which promote long-term SSC self-renewal. Using a SSC culture system, we have recently reported that Wnt5a promotes SSC self-renewal through a ?-catenin-independent Wnt mechanism whereas the ?-catenin-dependent Wnt pathway is not active in SSCs. In contrast, another study has reported that Wnt3a promotes SSC self-renewal through the ?-catenin-dependent pathway, as it can stimulate the proliferation of a spermatogonia cell line. To reconcile these two contradictory reports, we assessed Wnt3a effects on SSCs and progenitor cells, rather than a cell line, in vitro. We observed that Wnt3a induced ?-catenin-dependent signalling in a large subset of germ cells and increased SSC numbers. However, further investigation revealed that cell populations with greater ?-catenin-signalling activity contained fewer SSCs. The increased maintenance of SSCs by Wnt3a coincided with more active cell cycling and the formation of germ cell aggregates, or communities, under feeder-free conditions. Therefore, the results of this study suggest that Wnt3a selectively stimulates proliferation of progenitors that are committed to differentiation or are in the process of exiting the SSC state, leading to enhanced formation of germ cell communities, which indirectly support SSCs and act as an in vitro niche. PMID:22761943

  19. Stem cells in veterinary medicine

    Microsoft Academic Search

    Lisa A Fortier; Alexander J Travis

    2011-01-01

    The stem cell field in veterinary medicine continues to evolve rapidly both experimentally and clinically. Stem cells are\\u000a most commonly used in clinical veterinary medicine in therapeutic applications for the treatment of musculoskeletal injuries\\u000a in horses and dogs. New technologies of assisted reproduction are being developed to apply the properties of spermatogonial\\u000a stem cells to preserve endangered animal species. The

  20. Stem Cell Transplants at Childbirth

    Microsoft Academic Search

    Paul R. Sanberg; Dong-Hyuk Park; Cesar V. Borlongan

    2010-01-01

    Autologous transplantation of stem cells is a natural phenomenon at birth in mammals via the umbilical cord. Here, we discuss\\u000a that a delay in the cord clamping may increase stem cell supply to the baby, thereby allowing an innate stem cell therapy\\u000a that can render acute benefits in the case of neonatal disease, as well as long-term benefits against age-related

  1. Metabolic oxidation regulates embryonic stem cell differentiation

    PubMed Central

    Yanes, Oscar; Clark, Julie; Wong, Diana M; Patti, Gary J; Sanchez-Ruiz, Antonio; Benton, H Paul; Trauger, Sunia A; Desponts, Caroline; Ding, Sheng; Siuzdak, Gary

    2010-01-01

    Metabolites offer an important unexplored complement to understanding the pluripotency of stem cells. Using mass spectrometry-based metabolomics, we show that embryonic stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. By monitoring the reduced and oxidized glutathione ratio as well as ascorbic acid levels, we demonstrate that the stem cell redox status is regulated during differentiation. Based on the oxidative biochemistry of the unsaturated metabolites, we experimentally manipulated specific pathways in embryonic stem cells while monitoring the effects on differentiation. Inhibition of the eicosanoid signaling pathway promoted pluripotency and maintained levels of unsaturated fatty acids. In contrast, downstream oxidized metabolites (e.g., neuroprotectin D1) and substrates of pro-oxidative reactions (e.g., acyl-carnitines), promoted neuronal and cardiac differentiation. We postulate that the highly unsaturated metabolome sustained by stem cells makes them particularly attuned to differentiate in response to in vivo oxidative processes such as inflammation. PMID:20436487

  2. Modeling Stem Cell Induction Processes

    E-print Network

    Grácio, Filipe

    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 ...

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

    SciTech Connect

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

    1991-02-01

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

  4. Engineering stem cells for future medicine.

    PubMed

    Ricotti, Leonardo; Menciassi, Arianna

    2013-03-01

    Despite their great potential in regenerative medicine applications, stem cells (especially pluripotent ones) currently show a limited clinical success, partly due to a lack of biological knowledge, but also due to a lack of specific and advanced technological instruments able to overcome the current boundaries of stem cell functional maturation and safe/effective therapeutic delivery. This paper aims at describing recent insights, current limitations, and future horizons related to therapeutic stem cells, by analyzing the potential of different bioengineering disciplines in bringing stem cells toward a safe clinical use. First, we clarify how and why stem cells should be properly engineered and which could be in a near future the challenges and the benefits connected with this process. Second, we identify different routes toward stem cell differentiation and functional maturation, relying on chemical, mechanical, topographical, and direct/indirect physical stimulation. Third, we highlight how multiscale modeling could strongly support and optimize stem cell engineering. Finally, we focus on future robotic tools that could provide an added value to the extent of translating basic biological knowledge into clinical applications, by developing ad hoc enabling technologies for stem cell delivery and control. PMID:23380842

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

    PubMed

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

    2006-01-01

    Intervertebral disc (IVD) degeneration, a common cause of low back pain in humans, is a relentlessly progressive phenomenon with no currently available effective treatment. In an attempt to solve this dilemma, we transplanted autologous mesenchymal stem cells (MSCs) from bone marrow into a rabbit model of disc degeneration to determine if stem cells could repair degenerated IVDs. LacZ expressing MSCs were transplanted to rabbit L2-L3, L3-L4 and L4-L5 IVDs 2 weeks after induction of degeneration. Changes in disc height by plain radiograph, T2-weighted signal intensity in magnetic resonance imaging (MRI), histology, immunohistochemistry and matrix associated gene expressions were evaluated between normal controls (NC) without operations, sham operated with only disc degeneration being induced, and MSC-transplanted animals for a 24-week period. Results showed that after 24 weeks post-MSC transplantation, degenerated discs of MSC-transplanted group animals regained a disc height value of about 91%, MRI signal intensity of about 81%, compared to NC group discs. On the other hand, sham-operated group discs demonstrated the disc height value of about 67% and MRI signal intensity of about 60%. Macroscopic and histological evaluations confirmed relatively preserved nucleus with circular annulus structure in MSC-transplanted discs compared to indistinct structure seen in sham. Restoration of proteoglycan accumulation in MSC-transplanted discs was suggested from immunohistochemistry and gene expression analysis. These data indicate that transplantation of MSCs effectively led to regeneration of IVDs in a rabbit model of disc degeneration as suggested in our previous pilot study. MSCs may serve as a valuable resource in cell transplantation therapy for degenerative disc disease. PMID:16112726

  6. Mechanotransduction: Tuning Stem Cells Fate

    PubMed Central

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

    2011-01-01

    It is a general concern that the success of regenerative medicine-based applications is based on the ability to recapitulate the molecular events that allow stem cells to repair the damaged tissue/organ. To this end biomaterials are designed to display properties that, in a precise and physiological-like fashion, could drive stem cell fate both in vitro and in vivo. The rationale is that stem cells are highly sensitive to forces and that they may convert mechanical stimuli into a chemical response. In this review, we describe novelties on stem cells and biomaterials interactions with more focus on the implication of the mechanical stimulation named mechanotransduction. PMID:24956164

  7. Cancer Stem Cells

    PubMed Central

    Yu, Zuoren; Pestell, Timothy G.; Lisanti, Michael P.; Pestell, Richard G.

    2012-01-01

    Cancer Stem Cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into an animal host. A number of cell surface markers such as CD44, CD24, and CD133 are often used to identify and enrich CSCs. A regulatory network consisting of microRNAs and Wnt/?-catenin, Notch, and Hedgehog signaling pathways controls the CSC properties. The clinical relevance of CSCs has been strengthened by emerging evidence, demonstrating that CSCs are resistant to conventional chemotherapy and radiation treatment and that CSCs are very likely to be the origin of cancer metastasis. CSCs are believed to be an important target for novel anti-cancer drug discovery. Herein we summarize the current understanding of CSCs, with a focus on the role of miRNA and epithelial mesenchymal transition (EMT), and discuss the clinical application of targeting CSCs for cancer treatment. PMID:22981632

  8. Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells.

    PubMed

    Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

    2015-04-01

    Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body ?-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to ?-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

  9. Stem Cell Glycolipids

    Microsoft Academic Search

    Makoto Yanagisawa

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

  10. Stem cell therapy: challenges ahead.

    PubMed

    Bhagavati, Satyakam

    2015-03-01

    Stem cells have generated great interest for their potential therapeutic use because of their capacity to self-renew indefinitely and to generate all cell lineages (pluripotency). Many diseases such as neurodegenerative disorders or diabetes are caused by loss of functionality or deficiency of a particular cell type. Stem cells differentiated into a specific cell type such as pancreatic ?-cells or neurons, for example, thus hold great promise for regenerative medicine. However, many challenges have to be overcome before stem cell therapy can become a viable clinical approach. PMID:24992980

  11. STEM CELLS 2014;00:0000 www.StemCells.com AlphaMed Press 2014 EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS

    E-print Network

    Feng, Jian

    reduced in induced pluripotent stem cell (iPSC)derived TH + or TH neurons from PD patients neurons by stabilizing microtubules. STEM CELLS 2014; 00:000­000 INTRODUCTION The locomotorSTEM CELLS 2014;00:0000 www.StemCells.com ©AlphaMed Press 2014 EMBRYONIC STEM CELLS

  12. Background Information 1. What are stem cells?

    E-print Network

    Rambaut, Andrew

    Background Information 1. What are stem cells? 2. What might stem cell research achieve? 3. Why we need to continue research using embryonic stem cells? 4. Time taken for discoveries 5. Examples of stem cell therapies in clinical trials 6. Patentability of human embryonic stem cell therapies 7. Creation

  13. Stem cells in gastroenterology and hepatology

    Microsoft Academic Search

    Michael Quante; Timothy C. Wang

    2009-01-01

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

  14. Stem Cell Basics About this document

    E-print Network

    Bandettini, Peter A.

    1 Stem Cell Basics About this document This primer on stem cells is intended for anyone who wishes to learn more about the biological properties of stem cells, the important questions about stem cells that are the focus of scientific research, and the potential use of stem cells in research and in treating disease

  15. Effect of hydroxyapatite nanocrystals functionalized with lactoferrin in osteogenic differentiation of mesenchymal stem cells.

    PubMed

    Montesi, Monica; Panseri, Silvia; Iafisco, Michele; Adamiano, Alessio; Tampieri, Anna

    2015-01-01

    Lactoferrin (LF) is a bioactive glycoprotein that became recently interesting in the field of bone regeneration for its modulatory effect on bone cells. On the basis of this evidence this work aims to functionalize biomimetic hydroxyapatite (HA) nanocrystals with LF to study their effect on osteogenic differentiation of mesenchymal stem cells (MSCs). The orientation of LF on the HA surface was analyzed by spectroscopic and thermal techniques. Three samples with different amounts of LF attached to HA nanocrystals were tested in vitro. The combined effect of HA and LF on MSC proliferation and morphology, alkaline phosphatase (ALP) activity, and gene expression were evaluated at different time points. The sample with the lowest LF amount showed the best bioactivity probably due to the formation of a single layer of protein with a better molecular orientation. Coupling of HA-LF did not affect cell proliferation and morphology, while analysis of HA-LF on ALP activity and messenger RNA expression of the selected genes, demonstrated the role of HA-LF in the induction of osteogenic markers. HA-LF represents a promising system to be used to manufacture bioactive functional materials in tissue engineering (as scaffolds, injectable cements, or coatings for metallic implants) with enhanced anabolic activity to treat bone diseases. PMID:24639083

  16. Effect of liraglutide on proliferation and differentiation of human adipose stem cells.

    PubMed

    Cantini, Giulia; Di Franco, Alessandra; Samavat, Jinous; Forti, Gianni; Mannucci, Edoardo; Luconi, Michaela

    2015-02-15

    Glucagon-Like Peptide-1 (GLP-1) receptor agonists, used as glucose-lowering drugs, also induce weight loss by inhibiting food intake. The present study was aimed at the assessment of the in vitro effects of the GLP-1 receptor agonist liraglutide on proliferation and differentiation of human adipose stem cells (ASC) obtained from subcutaneous adipose tissue of morbidly obese subjects undergoing bariatric surgery. Liraglutide (10-100?nM) significantly inhibited ASC proliferation and viability, with a maximum effect at 6 days of culture (45% and 50%, for liraglutide 10 and 100?nM, respectively); the effect was reverted by exendin 9-39. Glucose uptake was significantly reduced by liraglutide in a dose dependent manner. Treatment with liraglutide reduced intracellular lipid accumulation in differentiating ASC, together with FABP-4 mRNA expression (-18%, -23%, -46%, for 1?nM, 10?nM and 100?nM, respectively), whereas it stimulated adiponectin (APN) expression (1.86-, 2.64-, 2.28-fold increase, for 1?nM, 10?nM and 100?nM, respectively). Liraglutide exerts effects on human adipose cell precursors, inhibiting proliferation and differentiation, while stimulating the expression of the insulin-sensitizing adipokine APN. These effects could contribute to the actions of GLP-1 receptor agonists on body weight and insulin sensitivity. PMID:25575456

  17. The effects of triclosan on pluripotency factors and development of mouse embryonic stem cells and zebrafish.

    PubMed

    Chen, Xiaojiao; Xu, Bo; Han, Xiumei; Mao, Zhilei; Chen, Minjian; Du, Guizhen; Talbot, Prue; Wang, Xinru; Xia, Yankai

    2015-04-01

    Triclosan (TCS) poses potential risks to reproduction and development due to its endocrine-disrupting properties. However, the mechanism of TCS's effects on early embryonic development is little known. Embryonic stem cells (ESC) and zebrafish embryos provide valuable models for testing the toxic effects of environmental chemicals on early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to TCS for 24 h, and general cytotoxicity and the effect of TCS on pluripotency were then evaluated. In addition, zebrafish embryos were exposed to TCS from 2- to 24-h post-fertilization (hpf), and their morphology was evaluated. In mESC, alkaline phosphatase staining was significantly decreased after treatment with the highest concentration of TCS (50 ?M). Although the expression levels of Sox2 mRNA were not changed, the mRNA levels of Oct4 and Nanog in TCS-treated groups were significantly decreased compared to controls. In addition, the protein levels of Oct4, Sox2 and Nanog were significantly reduced in response to TCS treatment. MicroRNA (miR)-134, an expression inhibitor of pluripotency markers, was significantly increased in TCS-treated mESC. In zebrafish experiments, after 24 hpf of treatment, the controls had developed to the late stage of somitogenesis, while embryos exposed to 300 ?g/L of TCS were still at the early stage of somitogenesis, and three genes (Oct4, Sox2 and Nanog) were upregulated in treated groups when compared with the controls. The two models demonstrated that TCS may affect early embryonic development by disturbing the expression of the pluripotency markers (Oct4, Sox2 and Nanog). PMID:24879426

  18. Effect of nanodiamond modification of siloxane surfaces on stem cell behaviour

    NASA Astrophysics Data System (ADS)

    Keremidarska, M.; Hikov, T.; Radeva, E.; Pramatarova, L.; Krasteva, N.

    2014-12-01

    Mesenchymal stem cells (MSCs) hold a great promise for use in many cell therapies and tissue engineering due to their remarkable potential to replicate indefinitely and differentiate into various cell types. Many efforts have been put to study the factors controlling stem cell differentiation. However, still little knowledge has been gained to what extent biomaterials properties influence stem cell adhesion, growth and differentiation. Research utilizing bone marrow-derived MSCs has concentrated on development of specific materials which can enhance specific differentiation of stem cells e.g. osteogenic and chondrogenic. In the present work we have modified an organosilane, hexamethyldisiloxane (HMDS) with detonation nanodiamond (DND) particles aiming to improve adhesion, growth and osteodifferentiation of rat mesenchymal stem cells. HMDS/DND films were deposited on cover glass using two approaches: premixing of both compounds, followed by plasma polymerization (PP) and PP of HMDS followed by plasma deposition of DND particles. We did not observe however an increase in rMSCs adhesion and growth on DND-modified PPHMDS surfaces compared to unmodified PPHMDS. When we studied alkaline phosphatase (ALP) activity, which is a major sign for early osteodifferentiation, we found the highest ALP activity on the PPHMDS/DND material, prepared by consequent deposition while on the other composite material ALP activity was the lowest. These results suggested that DND-modified materials were able to control osteodifferention in MSCs depending on the deposition approach. Modification of HMDS with DND particles by consequent plasma deposition seems to be a promising approach to produce biomaterials capable to guide stem cell differentiation toward osteoblasts and thus to be used in bone tissue engineering.

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

    NASA Astrophysics Data System (ADS)

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

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

  20. University of Michigan developmental cancer stem cell vaccine shows antitumor effect

    Cancer.gov

    Scientists from the University of Michigan Comprehensive Cancer Center may have discovered a new paradigm for immunotherapy against cancer by priming antibodies and T cells with cancer stem cells, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

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

    PubMed Central

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

    2014-01-01

    Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF) which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs) strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer. PMID:24595237

  2. Locally induced neural stem cells\\/pluripotent stem cells for in vivo cell replacement therapy

    Microsoft Academic Search

    Ti-Fei Yuan; Oscar Arias-Carrión

    2008-01-01

    Neural stem cells hold the key to innovative new treatments for age-associated degeneration and traumatic injury to the brain and spinal cord. We hypothesized that the in vivo induced pluripotent stem cells or neural stem cells through \\

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

    PubMed Central

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

    2014-01-01

    Aim of work: To demonstrate the bleomycin induced histological changes in the lung and the possible protective and/or therapeutic effect of stem cell therapy. Materials and methods: Study was carried out on 36 adult male albino rats, classified into 4 groups: group I (control), group II (bleomycin treated group), group III (early stem cell treated group: immediately after bleomycin), group IV (late stem cell treated group: 7 days after bleomycin). Sections were taken at the 14th day of experiment. stained with Hematoxylin and Eosin, Masson’s trichrome, immunohistochemichal stains for ?-SMA & PCNA. Sections were examined by light & immunofluroscent microscopy. Area percent of collagen fibers, area percent & optical density of ?-SMA immunopositive cells were measured as well as the number of H&E and PCNA stained pneumocytes type II was counted. Results: Group II showed, thickening of septa, extravasation of blood, dividing pneumocytes type II cells with acinar formation, cellular infiltration, fibroblast cells, almost complete loss of normal lung architecture in certain fields, consolidation and replacement of the lung tissue with fibrous tissue in other fields. Restoring of lung tissue with significant decrease in mean area % of collagen fibers, ?-SMA immunopositive cells were detected in group III. Conclusions: Early treatment with bone marrow derived mesenchymal stem cells (BMSCs) immediately after bleomycin administration showed a significant reduction in fibrotic changes, however the late treatment with BMSCs (7 days) after bleomycin administration showed non significant results. PMID:24921026

  4. Preconditioning Strategy in Stem Cell Transplantation Therapy

    PubMed Central

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

    2013-01-01

    Stem cell transplantation therapy has emerged as a promising regenerative medicine for ischemic stroke and other neurodegenerative disorders. However, many issues and problems remain to be resolved before successful clinical applications of the cell-based therapy. To this end, some recent investigations have sought to benefit from well-known mechanisms of ischemic/hypoxic preconditioning. Ischemic/hypoxic preconditioning activates endogenous defense mechanisms that show marked protective effects against multiple insults found in ischemic stroke and other acute attacks. As in many other cell types, a sub-lethal hypoxic exposure significantly increases the tolerance and regenerative properties of stem cells and progenitor cells. So far, a variety of preconditioning triggers have been tested on different stem cells and progenitor cells. Preconditioned stem cells and progenitors generally show much better cell survival, increased neuronal differentiation, enhanced paracrine effects leading to increased trophic support, and improved homing to the lesion site. Transplantation of preconditioned cells helps to suppress inflammatory factors and immune responses, and promote functional recovery. Although the preconditioning strategy in stem cell therapy is still an emerging research area, accumulating information from reports over the last few years already indicates it as an attractive, if not essential, prerequisite for transplanted cells. It is expected that stem cell preconditioning and its clinical applications will attract more attention in both the basic research field of preconditioning as well as in the field of stem cell translational research. This review summarizes the most important findings in this active research area, covering the preconditioning triggers, potential mechanisms, mediators, and functional benefits for stem cell transplant therapy. PMID:23914259

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

    PubMed Central

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

    2012-01-01

    Purpose The molecular markers cluster of differentiation (CD)24, CD44, adenosine tri-phosphate (ATP) binding cassette protein G2 (ABCG2), and epithelial cell adhesion molecule (EpCAM) are widely used, individually or in combination, to characterize some types of cancer stem cells. In this study we characterized the EpCAM+ retinoblastoma (RB) cells for their cancer stem-like properties in vitro. Additionally, we targeted RB tumor cells via redirecting T cells using bispecific EpCAM×CD3 antibody. Methods Flow cytometry was used to study the co-expression of EpCAM with putative cancer stem cell markers, such as CD44, CD24, and ABCG2, in RB primary tumors. In vitro methyl thiazol tetrazolium (MTT) assay, invasion assay, and neurosphere formation assay were performed to characterize EpCAM+ cells for their cancer stem/progenitor cell-like properties. We assessed the in vitro efficacy of bispecific EpCAM×CD3 antibody on RB tumor cell proliferation and validated the results by evaluating effector cytokine production in the culture medium with the ELISA method. Results EpCAM was co-expressed with all cancer stem cell markers (CD44, CD24, and ABCG2) in primary RB tumors. EpCAM+ cells showed significantly higher proliferative invasive potential and neurosphere formation in vitro compared to EpCAM– Y79 cells. EpCAM+ cells showed higher ?-catenin expression compared to EpCAM? cells. EpCAM×CD3 significantly retarded proliferation of RB primary tumor cells. EpCAM×CD3 effectively induced the secretion of effector cytokines, such as interferon (IFN)-?, tumor necrosis factor (TNF)-?, interleukin (IL)-10, IL-2, and transforming growth factor (TGF)-?1, and also perforin levels by pre-activated lymphocytes. Conclusions EpCAM might be a novel cancer stem cell marker in RB. EpCAM×CD3 antibody redirecting T cells to attack RB tumor cells may prove effective in RB management. Further preclinical studies are needed to confirm the initial findings of our study. PMID:22328825

  6. Stem cell tracking using iron oxide nanoparticles

    PubMed Central

    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. PMID:24729700

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

    PubMed Central

    2013-01-01

    Background Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods. Results We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as ?-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration. Conclusions We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also for in vitro applications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells. PMID:23870169

  8. Harvard Stem Cell Institute

    NSDL National Science Digital Library

    The Harvard Stem Cell Institute (HSCI) was formed in 2004 to "draw Harvard's resources together by establishing a cooperative community of scientists and practitioners, by developing new ways to fund and support research, and by promoting opportunities for open communication and education." Their website features videos of HSCI scientists speaking about their selected disease programs. Visitors can click on a video as it appears, or they can wait for one of the next videos in the rotation. To read about the disease programs, visitors can click on the "Research" tab near the top of the page, and then select the "Research Programs" link to read about the different programs and the lead researcher. Research programs include the "Blood Disease Program", "Cancer Program", "Cardiovascular Disease Program", "Kidney Disease Program", "Nervous System Diseases Program", and the "Translational Research Program". The "Resources" tab near the top of the page has video of a great series of education sessions that are held quarterly by HSCI, and which address the medical, religious, economic, and public policy concerns that stem cell research presents. There are eight sessions to watch, and each runs longer than an hour, so each topic is covered in exquisite detail.

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

    PubMed

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

    2014-01-30

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

  10. Distinct effects of caudalizing factors on regional specification of embryonic stem cell-derived neural precursors.

    PubMed

    Irioka, Takashi; Watanabe, Kiichi; Mizusawa, Hidehiro; Mizuseki, Kenji; Sasai, Yoshiki

    2005-01-01

    Recent embryological studies have implicated several "caudalizing factors" in the caudal specification of the central nervous system (CNS). In this study, we have examined the effects of three candidate caudalizing factors on neural precursors induced from embryonic stem (ES) cells by the stromal cell-derived inducing activity (SDIA) method. Among retinoic acid (RA), Wnt and FGF signals, RA causes the strongest level of caudalization: inducing suppression of forebrain differentiation and promotion of caudal CNS specification. Obvious suppression of the telencephalic marker Bf1 and that of the forebrain marker Otx2 occur at 2x10(-8) and 2x10(-7) M, respectively. Activation of the caudal marker genes such as Hoxb9 is observed in a dose-dependent manner over the range of 2x10(-9)-2x10(-6) M. Suppression of the forebrain genes has a narrow critical period of RA response during the early culture phase. In contrast, significant induction of the caudal genes is evoked by a 1-day exposure to RA at any time between days 3 and 8. RA treatment not only induces caudal specification but also inhibits differentiation of ventral CNS tissues, particularly of floor plate cells. FGF4 induces partial caudalization while Wnt-3A exhibits weak caudalizing activities only in the presence of RA. These findings provide useful information on the proper selection of combination of signaling molecules, doses and timing for steering ES cell differentiation by caudalizing factors into caudal neural fates. PMID:15617756

  11. Effect of Propofol on microRNA Expression Profile in Adipocyte-Derived Adult Stem Cells.

    PubMed

    Kim, Jung-Ho; Kim, Bo-Kyeom; Kim, Dong-Wook; Shin, Hye-Young; Yu, Soo-Bong; Kim, Doo-Sik; Ryu, Sie-Jeong; Kim, Kyung-Han; Jang, Hee-Kyung; Kim, Ju-Deok

    2014-12-01

    MicroRNA (miRNA) pathways have been implicated in stem cell regulation. This study investigated the molecular effects of propofol on adipocyte stem cells (ASCs) by analyzing RNA expression arrays. Human ASCs were isolated by use of a liposuction procedure. ASCs were treated with saline, 50 µM propofol, or 100 µM propofol in culture media for 3 hours. After the isolation of total RNA, the expression of 76 miRNAs was evaluated with peptide nucleic acid-miRNA array analysis through denaturation and hybridization processes. Treatment with 50 µM propofol resulted in significant down-regulation of expression of 18 miRNAs and upregulation of expression of 25 miRNAs; 100 µM propofol resulted in significant downregulation of expression of 14 miRNAs and upregulation of expression of 29 miRNAs. The lowest expression was seen for miR-204, which was 0.07-fold with 50 µM propofol and 0.18-fold with 100 µM propofol. The highest expression was seen for miR-208b, which was 11.23-fold with 50 µM propofol and 11.20-fold with 100 µM propofol. Expression patterns of miRNAs were not significantly different between 50 µM and 100 µM propofol treatment. The results of this study suggest that propofol is involved in altering the miRNA expression level in human ASCs. Additional research is necessary to establish the functional effect of miRNA alteration by propofol. PMID:25568843

  12. Effect of Propofol on microRNA Expression Profile in Adipocyte-Derived Adult Stem Cells

    PubMed Central

    Kim, Jung-Ho; Kim, Bo-Kyeom; Kim, Dong-Wook; Shin, Hye-Young; Yu, Soo-Bong; Kim, Doo-Sik; Ryu, Sie-Jeong; Kim, Kyung-Han; Jang, Hee-Kyung

    2014-01-01

    MicroRNA (miRNA) pathways have been implicated in stem cell regulation. This study investigated the molecular effects of propofol on adipocyte stem cells (ASCs) by analyzing RNA expression arrays. Human ASCs were isolated by use of a liposuction procedure. ASCs were treated with saline, 50 µM propofol, or 100 µM propofol in culture media for 3 hours. After the isolation of total RNA, the expression of 76 miRNAs was evaluated with peptide nucleic acid-miRNA array analysis through denaturation and hybridization processes. Treatment with 50 µM propofol resulted in significant down-regulation of expression of 18 miRNAs and upregulation of expression of 25 miRNAs; 100 µM propofol resulted in significant downregulation of expression of 14 miRNAs and upregulation of expression of 29 miRNAs. The lowest expression was seen for miR-204, which was 0.07-fold with 50 µM propofol and 0.18-fold with 100 µM propofol. The highest expression was seen for miR-208b, which was 11.23-fold with 50 µM propofol and 11.20-fold with 100 µM propofol. Expression patterns of miRNAs were not significantly different between 50 µM and 100 µM propofol treatment. The results of this study suggest that propofol is involved in altering the miRNA expression level in human ASCs. Additional research is necessary to establish the functional effect of miRNA alteration by propofol. PMID:25568843

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

    PubMed Central

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

    2013-01-01

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

  14. Breast cancer stem cells

    PubMed Central

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumors are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs). Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarize what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically. PMID:23986719

  15. Alternative Embryonic Stem Cell Sources

    Microsoft Academic Search

    Tomo Šari?; Narges Zare Mehrjardi; Jürgen Hescheler

    \\u000a Pluripotency refers to the ability of a cell to differentiate in vivo or in vitro to practically all cell types of an adult\\u000a organism. In vivo, pluripotent stem cells exist only transiently in early embryos. However, when explanted the in vitro counterparts\\u000a of these cells, known as embryonic stem (ES) cells, can be maintained indefinitely in culture in undifferentiated state

  16. History of Cancer Stem Cells

    Microsoft Academic Search

    Stewart Sell

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

  17. The new stem cell biology.

    PubMed Central

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

    2002-01-01

    Recent studies have indicated that bone marrow stem cells are capable of generating muscle, cardiac, hepatic, renal, and bone cells. Purified hematopoietic stem cells have generated cardiac and hepatic cells and reversed disease manifestations in these tissues. Hematopoietic stem cells also alter phenotype with cell cycle transit or circadian phase. During a cytokine stimulated cell cycle transit, reversible alterations of differentiation and engraftment occur. Primitive hematopoietic stem cells express a wide variety of adhesion and cytokine receptors and respond quickly with migration and podia extensions on exposure to cytokines. These data suggest an "Open Chromatin" model of stem cell regulation in which there is a fluctuating continuum in the stem cell/progenitor cell compartments, rather than a hierarchical relationship. These observations, along with progress in using low dose treatments and tolerization approaches, suggest many new therapeutic strategies involving stem cells and the creation of a new medical specialty; stemology. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:12053709

  18. Adult Stem and Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Geraerts, Martine; Verfaillie, Catherine M.

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

  19. 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

  20. Bioprinting for stem cell research

    PubMed Central

    Tasoglu, Savas; Demirci, Utkan

    2012-01-01

    Recently, there has been a growing interest to apply bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized proteins can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cell of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. PMID:23260439

  1. Stem cells for spine surgery.

    PubMed

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

    2015-01-26

    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

  2. Stem Cells behind the Barrier.

    PubMed

    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

  3. Xanthosine administration does not affect the proportion of epithelial stem cells in bovine mammary tissue, but has a latent negative effect on cell proliferation.

    PubMed

    Rauner, Gat; Barash, Itamar

    2014-10-15

    The challenge in manipulating the proportion of somatic stem cells lies in having to override tissue homeostasis. Xanthosine infusion via the teat canal has been reported to augment the number of label-retaining cells in the mammary gland of 3-month-old bovine calves. To further delineate xanthosine?s effect on defined stem cells in the mammary gland of heifers-which are candidates for increased prospective milk production following such manipulation-bovine mammary parenchymal tissue was transplanted and integrated into the cleared mammary fat pad of immunodeficient mice. Xanthosine administration for 14 days did not affect the number of label-retaining cells after 10- and 11-week chases. No change in stem cell proportion, analyzed according to CD49f and CD24 expression, was noted. Clone formation and propagation rate of cultured cells, as well as expression of stem cell markers, were also unaffected. In contrast, a latent 50% decrease in bovine mammary cell proliferation rate was observed 11 weeks after xanthosine administration. Tumor development in mice was also limited by xanthosine administration. These effects may have resulted from an initial decrease in expression of the rate-limiting enzyme in guanine synthesis, IMPDH. The data indicate that caution should be exerted when considering xanthosine for stem cell manipulation. PMID:24992045

  4. Cell Stem Cell Endogenous Bone Marrow MSCs

    E-print Network

    Mootha, Vamsi K.

    of cultured cells (Sacchetti et al., 2007). Similar multipotent MSCs can be isolated from mouse bone marrowCell Stem Cell Article Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants Street, Boston, MA 02114, USA 4Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA

  5. Cell Stem Cell Induction of Multipotential Hematopoietic

    E-print Network

    Collins, James J.

    patients with hematologic diseases, including Fanconi anemia (Mu¨ ller et al., 2012), sickle cell anemiaCell Stem Cell Article Induction of Multipotential Hematopoietic Progenitors from Human Pluripotent Stem Cells via Respecification of Lineage-Restricted Precursors Sergei Doulatov,1,2 Linda T. Vo,1

  6. Developmental Cell Sox2+ Stem Cells Contribute

    E-print Network

    Klein, Ophir

    Developmental Cell Article Sox2+ Stem Cells Contribute to All Epithelial Lineages of the Tooth via of the incisor in the labial cervical loop. Here, we show that the transcription factor Sox2 is a specific marker for these stem cells. Sox2+ cells became restricted to the labial cervical loop during tooth morphogenesis

  7. Stem Cells for Cell-Based Therapies

    NSDL National Science Digital Library

    Lauren Pecorino (University of Greenwich, U.K.; )

    2001-07-01

    The issue-focused, peer-reviewed article explains how stem cells have the potential to cure many human diseases because they are: like blank cells - they can become any cell in the human body, enduring - embryos, in particular, can provide an endless supply of stem cells, and regenerative - they can be used as a live source of self-repair.

  8. R-ESHAP plus pegfilgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory diffuse large B-cell lymphoma.

    PubMed

    Montoro, Juan; Andreola, Giovanna; Gardellini, Angelo; Babic, Aleksandra; Negri, Mara; Frungillo, Niccolň; Martinelli, Giovanni; Laszlo, Daniele

    2014-06-01

    Stem cell (SC) mobilization is significantly influenced by the mobilization schedule in patients with lymphoma. We evaluated data from 30 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) undergoing SC mobilization. All received R-ESHAP plus a single dose of pegfilgrastim. All patients collected ? 2 × 10(6) CD34+cells/kg, 80% of them at least 5 × 10(6) CD34+cells/kg. Adverse effects of the regimen included myelosuppression and neutropenic fever. Herein, our results suggest that R-ESHAP plus pegfilgrastim is a highly effective mobilization strategy in patients affected by DLBCL associated with a low incidence of adverse events. PMID:24751603

  9. The effects of human keratinocyte coculture on human adipose-derived stem cells.

    PubMed

    Seo, Bommie F; Kim, Ki J; Kim, Min K; Rhie, Jong W

    2014-08-01

    The potential for adipose-derived stem cells to differentiate into keratinocyte-like cells has recently been receiving attention, stemming from the hypothesis that a bioengineered skin may be manufactured from these readily available mesenchymal stem cells. This study was conducted to evaluate the influence of human keratinocyte non-contact coculture on hADSCs. Human epidermal keratinocytes and hADSCs obtained by lipoaspiration were cultured in keratinogenic growth media, which were divided into the following groups: human adipose-derived stem cell (hADSC) monoculture, non-contact coculture of hADSCs and human keratinocytes and keratinocyte monoculture. Cell proliferation was assessed, and keratogenicity was analysed through immunocytochemistry and polymerase chain reaction of early, intermediate and late keratogenic markers. hADSCs cocultured with keratinocytes displayed enhanced proliferation compared with the monoculture group. After a 7-day coculture period, immunohistochemistry and polymerase chain reaction findings revealed the presence of specific keratinocyte markers in the coculture group. This study demonstrates that hADSCs cocultured with keratinocytes have the capacity to transdifferentiate into keratinocyte lineage cells, and suggests that adipose tissue may be a source of keratinocytes that may further be used in structuring the bioengineered skin. PMID:25091634

  10. Stem Cell Transplant Patients and Fungal Infections

    MedlinePLUS

    ... gov . Fungal Diseases Share Compartir Stem Cell Transplant Patients and Fungal Infections As a stem cell transplant ... Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because they are ...

  11. What's It Like to Donate Stem Cells?

    MedlinePLUS

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

  12. FDA Warns About Stem Cell Claims

    MedlinePLUS

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Claims Search the Consumer Updates Section Researchers hope ... blood-forming system. back to top Regulation of Stem Cells FDA regulates stem cells in the U.S. to ...

  13. Effects of lentiviral infection of mesenchymal stem cells on the expression of octamer transcription factor 4

    PubMed Central

    CHANG, JING; TANG, LI; LEI, HAN; ZHANG, XIAO-GANG; ZUO, ZHONG; HUANG, WEI; FU, HANG

    2014-01-01

    The present study aimed to investigate the effects of lentiviral infection of human umbilical cord mesenchymal stem cells (hUCMSCs) on the expression of octamer transcription factor 4 (Oct4). hUCMSCs were infected with lentivirus carrying the green fluorescent protein gene (GFP) at different multiplicities of infection (MOI), and the optimal MOI was determined by flow cytometry; the proliferation of non-infected and GFP-carrying lentivirus-infected hUCMSCs was evaluated by the MTT assay; and the expression of the Oct4 gene was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence staining in hUCMSCs cultured in vitro for eight weeks. Positive GFP staining of hUCMSCs was estimated at >75% at 48 h following infection with the GFP-carrying lentivirus (MOI = 20); no effect on hUCMSC proliferation was detected by the MTT assay following the infection; immunofluorescence analysis detected positive Oct4 expression in the cell nuclei at two and eight weeks of culture, while the relative expression of Oct4 assessed by qRT-PCR was 0.9075±0.0124. The GFP gene carried by the lentivirus was successfully expressed in hUCMSCs and had no significant effect on Oct4 expression, which lays a solid foundation for future studies investigating gene functions via the use of exogenous markers. PMID:25174942

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

    Microsoft Academic Search

    Mohamadreza Baghaban Eslaminejad; Mahmood Talkhabi; Bahman Zeynali

    2008-01-01

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

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

    Microsoft Academic Search

    Rokhaya Diop; Song Li

    2011-01-01

    \\u000a Although the field of vascular tissue engineering has made tremendous advances in the past decade, several complications have\\u000a yet to be overcome in order to produce biocompatible small-diameter vascular conduits with long-term patency. Stem cells and\\u000a progenitor cells represent potential cell sources in the development of autologous (or allogeneic), nonthrombogenic vascular\\u000a grafts with mechanical properties comparable to native blood vessel.

  16. Effect of extracorporeal shock wave on proliferation and differentiation of equine adipose tissue-derived mesenchymal stem cells in vitro

    PubMed Central

    Raabe, O; Shell, K; Goessl, A; Crispens, C; Delhasse, Y; Eva, A; Scheiner-Bobis, G; Wenisch, S; Arnhold, S

    2013-01-01

    Mesenchymal stem cells are regarded as common cellular precursors of the musculoskeletal tissue and are responsible for tissue regeneration in the course of musculoskeletal disorders. In equine veterinary medicine extracorporeal shock wave therapy (ESWT) is used to optimize healing processes of bone, tendon and cartilage. Nevertheless, little is known about the effects of the shock waves on cells and tissues. Thus, the aim of this study was to investigate the influence of focused ESWT on the viability, proliferation, and differentiation capacity of adipose tissue-derived mesenchymal stem cells (ASCs) and to explore its effects on gap junctional communication and the activation of signalling cascades associated with cell proliferation and differentiation. ASCs were treated with different pulses of focused ESWT. Treated cells showed increased proliferation and expression of Cx43, as detected by means of qRT-PCR, histological staining, immunocytochemistry and western blot. At the same time, cells responded to ESWT by significant activation (phosphorylation) of Erk1/2, detected in western blots. No significant effects on the differentiation potential of the ASCs were evident. Taken together, the present results show significant effects of shock waves on stem cells in vitro. PMID:23671817

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

    PubMed

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

    2014-05-01

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

  18. The postnatal origin of adult neural stem cells and the effects of glucocorticoids on their genesis.

    PubMed

    Ortega-Martínez, Sylvia; Trejo, José L

    2015-02-15

    The relevance of adult neurogenesis in hippocampal function is well documented, as is the potential impact stress has on the adult neurogenic niche. Adult born neurons are generated from neural precursors in the dentate gyrus (DG), although the point in postnatal development that these cell precursors originate is not known. This is particularly relevant if we consider the effects stress may have on the development of neural precursors, and whether such effects on adult neurogenesis and behavior may persist in the long-term. We have analyzed the proportion of neural precursors in the adult murine hippocampus born on specific days during postnatal development using a dual birth-dating analysis, and we assessed their sensitivity to dexamethasone (DEX) on the peak day of cell generation. We also studied the consequences of postnatal DEX administration on adult hippocampal-dependent behavior. Postnatal day 6 (P6) is a preferred period for proliferating neural stem cells (NSCs) to become the precursors that remain in a proliferative state throughout adulthood. This window is independent of gender, the cell's location in the DG granule cell layer or their rostro-caudal position. DEX administration at P6 reduces the size of the adult NSC pool in the DG, which is correlated with poor learning/memory capacity and increased anxiety-like behavior. These results indicate that aNSCs are generated non-uniformly during postnatal development, with peak generation on day P6, and that stress receptor activation during the key period of postnatal NSC generation has a profound impact on both adult hippocampal neurogenesis and behavior. PMID:25446750

  19. Effects of Wharton’s jelly-derived mesenchymal stem cells on neonatal neutrophils

    PubMed Central

    Khan, Imteyaz; Zhang, Liying; Mohammed, Moiz; Archer, Faith E; Abukharmah, Jehan; Yuan, Zengrong; Rizvi, S Saif; Melek, Michael G; Rabson, Arnold B; Shi, Yufang; Weinberger, Barry; Vetrano, Anna M

    2015-01-01

    Background Mesenchymal stem cells (MSCs) have been proposed as autologous therapy for inflammatory diseases in neonates. MSCs from umbilical cord Wharton’s jelly (WJ-MSCs) are accessible, with high proliferative capacity. The effects of WJ-MSCs on neutrophil activity in neonates are not known. We compared the effects of WJ-MSCs on apoptosis and the expression of inflammatory, oxidant, and antioxidant mediators in adult and neonatal neutrophils. Methods WJ-MSCs were isolated, and their purity and function were confirmed by flow cytometry. Neutrophils were isolated from cord and adult blood by density centrifugation. The effects of neutrophil/WJ-MSC co-culture on apoptosis and gene and protein expression were measured. Results WJ-MSCs suppressed neutrophil apoptosis in a dose-dependent manner. WJ-MSCs decreased gene expression of NADPH oxidase-1 in both adult and neonatal neutrophils, but decreased heme oxygenase-1 and vascular endothelial growth factor and increased catalase and cyclooxygenase-2 in the presence of lipopolysaccharide only in adult cells. Similarly, generation of interleukin-8 was suppressed in adult but not neonatal neutrophils. Thus, WJ-MSCs dampened oxidative, vascular, and inflammatory activity by adult neutrophils, but neonatal neutrophils were less responsive. Conversely, Toll-like receptor-4, and cyclooxygenase-2 were upregulated in WJ-MSCs only in the presence of adult neutrophils, suggesting an inflammatory MSC phenotype that is not induced by neonatal neutrophils. Conclusion Whereas WJ-MSCs altered gene expression in adult neutrophils in ways suggesting anti-inflammatory and antioxidant effects, these responses were attenuated in neonatal cells. In contrast, inflammatory gene expression in WJ-MSCs was increased in the presence of adult but not neonatal neutrophils. These effects should be considered in clinical trial design before WJ-MSC-based therapy is used in infants. PMID:25678809

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

    SciTech Connect

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

    2010-09-10

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

  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. Effect of Iron Deficiency on c-kit+ Cardiac Stem Cells In Vitro

    PubMed Central

    Song, Dongqiang; Li, Yuanmin; Cao, Jiatian; Han, Zhihua; Gao, Lin; Xu, Zuojun; Yin, Zhaofang; Wang, Guifang; Fan, Yuqi; Wang, Changqian

    2013-01-01

    Aim Iron deficiency is a common comorbidity in chronic heart failure (CHF) which may exacerbate CHF. The c-kit+ cardiac stem cells (CSCs) play a vital role in cardiac function repair. However, much is unknown regarding the role of iron deficiency in regulating c-kit+ CSCs function. In this study, we investigated whether iron deficiency regulates c-kit+ CSCs proliferation, migration, apoptosis, and differentiation in vitro. Method All c-kit+ CSCs were isolated from adult C57BL/6 mice. The c-kit+ CSCs were cultured with deferoxamine (DFO, an iron chelator), mimosine (MIM, another iron chelator), or a complex of DFO and iron (Fe(III)), respectively. Cell migration was assayed using a 48-well chamber system. Proliferation, cell cycle, and apoptosis of c-kit+ CSCs were analyzed with BrdU labeling, population doubling time assay, CCK-8 assay, and flow cytometry. Caspase-3 protein level and activity were examined with Western blotting and spectrophotometric detection. The changes in the expression of cardiac-specific proteins (GATA-4,TNI, and ?-MHC) and cell cycle-related proteins (cyclin D1, RB, and pRB) were detected with Western blotting. Result DFO and MIM suppressed c-kit+ CSCs proliferation and differentiation. They also modulated cell cycle and cardiac-specific protein expression. Iron chelators down-regulated the expression and phosphorylation of cell cycle-related proteins. Iron reversed those suppressive effects of DFO. DFO and MIM didn’t affect c-kit+ CSCs migration and apoptosis. Conclusion Iron deficiency suppressed proliferation and differentiation of c-kit+ CSCs. This may partly explain how iron deficiency affects CHF prognosis. PMID:23762416

  3. Effective combination of aligned nanocomposite nanofibers and human unrestricted somatic stem cells for bone tissue engineering

    PubMed Central

    Bakhshandeh, Behnaz; Soleimani, Masoud; Ghaemi, Nasser; Shabani, Iman

    2011-01-01

    Aim: Bioartificial bone tissue engineering is an increasingly popular technique to solve bone defect challenges. This study aimed to investigate the interactions between matrix composition and appropriate cell type, focusing on hydroxyapatite (HA), to achieve a more effective combination for bone regeneration. Methods: Human unrestricted somatic stem cells (USSCs) were isolated from placental cord blood. The cellular and molecular events during the osteo-induction of USSCs were evaluated for 21 d under the following conditions: (1) in basal culture, (2) supplemented with hydroxyapatite nanoparticle (nHA) suspension, and (3) seeded on electrospun aligned nanofibrous poly-?-caprolactone/poly-L-lactic acid/nHA (PCL/PLLA/nHA) scaffolds. The scaffolds were characterized using scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR) and tensile test. Results: Maintenance of USSCs for 21 d in basal or osteogenic culture resulted in significant increase in osteoblast differentiation. With nHA suspension, even soluble osteo-inductive additives were ineffective, probably due to induced apoptosis of the cells. In contrast to the hindrance of proliferation by nHA suspension, the scaffolds improved cell growth. The scaffolds mimic the nanostructure of natural bone matrix with the combination of PLLA/PCL (organic phase) and HA (inorganic phase) offering a favorable surface topography, which was demonstrated to possess suitable properties for supporting USSCs. Quantitative measurement of osteogenic markers, enzymatic activity and mineralization indicated that the scaffolds did not disturb, but enhanced the osteogenic potential of USSCs. Moreover, the alignment of the fibers led to cell orientation during cell growth. Conclusion: The results demonstrated the synergism of PCL/PLLA/nHA nanofibrous scaffolds and USSCs in the augmentation of osteogenic differentiation. Thus, nHA grafted into PCL/PLLA scaffolds can be a suitable choice for bone tissue regeneration. PMID:21516135

  4. Effects of Tithonia diversifolia (Hemsl.) A. Gray Extract on Adipocyte Differentiation of Human Mesenchymal Stem Cells

    PubMed Central

    Di Giacomo, Claudia; Vanella, Luca; Sorrenti, Valeria; Santangelo, Rosa; Barbagallo, Ignazio; Calabrese, Giovanna; Genovese, Carlo; Mastrojeni, Silvana; Ragusa, Salvatore; Acquaviva, Rosaria

    2015-01-01

    Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae) is widely used in traditional medicine. There is increasing interest on the in vivo protective effects of natural compounds contained in plants against oxidative damage caused from reactive oxygen species. In the present study the total phenolic and flavonoid contents of aqueous, methanol and dichloromethane extracts of leaves of Tithonia diversifolia (Hemsl.) A. Gray were determined; furthermore, free radical scavenging capacity of each extract and the ability of these extracts to inhibit in vitro plasma lipid peroxidation were also evaluated. Since oxidative stress may be involved in trasformation of pre-adipocytes into adipocytes, to test the hypothesis that Tithonia extract may also affect adipocyte differentiation, human mesenchymal stem cell cultures were treated with Tithonia diversifolia aqueous extract and cell viability, free radical levels, Oil-Red O staining and western bolt analysis for heme oxygenase and 5'-adenosine monophoshate-activated protein kinase were carried out. Results obtained in the present study provide evidence that Tithonia diversifolia (Hemsl.) A. Gray exhibits interesting health promoting properties, resulting both from its free radical scavenger capacity and also by induction of protective cellular systems involved in cellular stress defenses and in adipogenesis of mesenchymal cells. PMID:25848759

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

    PubMed

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

    2014-08-01

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

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

    PubMed Central

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

    2013-01-01

    ?-catenin, an adherens junction component and key Wnt pathway effector, regulates numerous developmental processes and supports embryonic stem cell (ESC) pluripotency in specific contexts. The ?-catenin homologue ?-catenin (also known as Plakoglobin) is a constituent of desmosomes and adherens junctions and may participate in Wnt signaling in certain situations. Here, we use ?-catenin(+/+) and ?-catenin(?/?) mouse embryonic stem cells (mESCs) to investigate the role of ?-catenin in Wnt signaling and mESC differentiation. Although ?-catenin protein is markedly stabilized upon inhibition or ablation of GSK-3 in wild-type (WT) mESCs, efficient silencing of its expression in these cells does not affect ?-catenin/TCF target gene activation after Wnt pathway stimulation. Nonetheless, knocking down ?-catenin expression in WT mESCs appears to promote their exit from pluripotency in short-term differentiation assays. In ?-catenin(?/?) mESCs, GSK-3 inhibition does not detectably alter cytosolic ?-catenin levels and does not activate TCF target genes. Intriguingly, ?-catenin/TCF target genes are induced in ?-catenin(?/?) mESCs overexpressing stabilized ?-catenin and the ability of these genes to be activated upon GSK-3 inhibition is partially restored when wild-type ?-catenin is overexpressed in these cells. This suggests that a critical threshold level of total catenin expression must be attained before there is sufficient signaling-competent ?-catenin available to respond to GSK-3 inhibition and to regulate target genes as a consequence. WT mESCs stably overexpressing ?-catenin exhibit robust Wnt pathway activation and display a block in tri-lineage differentiation that largely mimics that observed upon overexpression of ?-catenin. However, ?-catenin overexpression appears to be more effective than ?-catenin overexpression in sustaining the retention of markers of naďve pluripotency in cells that have been subjected to differentiation-inducing conditions. Collectively, our study reveals a function for ?-catenin in the regulation of mESC differentiation and has implications for human cancers in which ?-catenin is mutated and/or aberrantly expressed. PMID:23724138

  7. Cell Stem Cell The Use of Fresh Embryos in Stem Cell Research

    E-print Network

    Cell Stem Cell Commentary The Use of Fresh Embryos in Stem Cell Research: Ethical and Policy Issues of poor quality, can provide sources of human embryonic stem cell lines. We consider why some donate for fresh embryo donation based on those of Canada. Introduction Stem cell investigators have sought

  8. Natural killer cells can exert a graft-vs-tumor effect in haploidentical stem cell transplantation for pediatric solid tumors.

    PubMed

    Pérez-Martínez, Antonio; de Prada Vicente, Inmaculada; Fernández, Lucía; González-Vicent, Marta; Valentín, Jaime; Martín, Roberto; Maxwell, Hannah; Sevilla, Julián; Vicario, José Luis; Díaz, Miguel Ángel

    2012-11-01

    Little progress has been made with regard to the survival of children with metastatic and refractory solid tumors. Preliminary data from haploidentical stem cell transplantation (haplo-SCT) suggested a clinically beneficial allograft-vs-tumor effect associated with natural killer cell (NK) donor-recipient mismatch. We hypothesized that interaction between activatory receptors on NK cells and their ligands on tumor cells could be also important. To evaluate the NK-cell-mediated allograft-vs-tumor effect, we conducted a pilot study of haplo-SCT on six children with refractory solid tumors. Our specific goal for this study was NKG2D-major histocompatibility complex class I-related chain A interaction. Tasks include specific immunoassays that support haplo-SCT in refractory solid tumors. Patients suffered from neuroblastoma (n = 1), Ewing sarcoma (n = 2), a desmoplastic tumor (n = 1), nasopharyngeal carcinoma (n = 1), and embryonal rhabdomyosarcoma (n = 1). Pretransplantation disease status showed progressive disease in 2 patients, partial remission in 2 patients, and complete remission in 2 patients. NK-cell mismatch was present in three donor-recipients. Ligands for NKG2D receptors, major histocompatibility complex class I-related chain A and UL16 binding protein 2 were overexpressed in six of six and four of six tumors, respectively. NK cells led early immune reconstitution. After haplo-SCT, three patients were in complete remission, one patient showed partial remission, and two patients were in stable disease. With a median follow-up of 14 months, three patients were alive and in complete remission, and three patients had died; two due to progressive disease and one of transplant-related toxicity. Blocking NKG2D-major histocompatibility complex class I-related chain A interaction in vitro reduced NK-cell cytotoxicity. Our preliminary results suggest a beneficial effect from haplo-SCT in refractory solid tumors. PMID:22771496

  9. Cancer stem cells and “stemness” genes in neuro-oncology

    Microsoft Academic Search

    Silvia K. Nicolis

    2007-01-01

    The main properties of stem cells include long-term self-renewal and the capacity to give rise to one or more types of differentiated progeny. Recently, much evidence was provided that leukemia and tumor maintenance and growth are sustained by a small proportion of cells exhibiting stem cell properties. In neural tumors, stem cells have been detected in glioblastoma, medulloblastoma and ependymoma.

  10. 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

  11. Distribution of Mesenchymal Stem Cells and Effects on Neuronal Survival and Axon Regeneration after Optic Nerve Crush and Cell Therapy

    PubMed Central

    Mesentier-Louro, Louise Alessandra; Zaverucha-do-Valle, Camila; da Silva-Junior, Almir Jordăo; Nascimento-dos-Santos, Gabriel; Gubert, Fernanda; de Figueirędo, Ana Beatriz Padilha; Torres, Ana Luiza; Paredes, Bruno D.; Teixeira, Camila; Tovar-Moll, Fernanda; Mendez-Otero, Rosalia; Santiago, Marcelo F.

    2014-01-01

    Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC) injected into the vitreous body in a model of optic nerve injury. Adult (3–5 months old) Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1? expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime. PMID:25347773

  12. Culture medium of bone marrow-derived human mesenchymal stem cells effects lymphatic endothelial cells and tumor lymph vessel formation

    PubMed Central

    ZHAN, JIE; LI, YAHONG; YU, JING; ZHAO, YUANYAUN; CAO, WENMING; MA, JIE; SUN, XIAOXIAN; SUN, LI; QIAN, HUI; ZHU, WEI; XU, WENRONG

    2015-01-01

    Human bone marrow mesenchymal stem cells (hBM-MSCs) favor tumor growth and metastasis in vivo and in vitro. Neovascularization is involved in several pathological conditions, including tumor growth and metastasis. Previous studies have demonstrated that human bone marrow MSC-derived conditioned medium (hBM-MSC-CM) can promote tumor growth by inducing the expression of vascular epidermal growth factor (VEGF) in tumor cells. However, the effect of BM-MSCs on tumor lymph vessel formation has yet to be elucidated. In the present study, the effect of BM-MSCs on processes involved in lymph vessel formation, including tube formation, migration and proliferation, was investigated in human-derived lymphatic endothelial cells (HDLECs). It was identified that hBM-MSC-CM promoted the tube formation and migration of HDLECs. In addition, tumor cells were revealed to participate in lymph vessel formation. In the present study, the SGC-7901, HGC-27 and GFP-MCF-7 cell lines were treated with hBM-MSC-CM. The results demonstrated that the expression of the lymph-associated markers, prospero homeobox protein 1 and VEGF receptor-3, were increased in the SGC-7901 and HGC-27 cell lines, but not in the GFP-MCF-7 cells. The tube formation assay demonstrated that the HGC-27 cells treated with hBM-MSC-CM for 20 days underwent tube formation. These findings indicate that hBM-MSC-CM can promote tube formation in HDLECs and HGC-27 cells, which may be associated with lymph vessel formation during tumor growth and metastasis. PMID:25663886

  13. Distribution of mesenchymal stem cells and effects on neuronal survival and axon regeneration after optic nerve crush and cell therapy.

    PubMed

    Mesentier-Louro, Louise Alessandra; Zaverucha-do-Valle, Camila; da Silva-Junior, Almir Jordăo; Nascimento-Dos-Santos, Gabriel; Gubert, Fernanda; de Figueirędo, Ana Beatriz Padilha; Torres, Ana Luiza; Paredes, Bruno D; Teixeira, Camila; Tovar-Moll, Fernanda; Mendez-Otero, Rosalia; Santiago, Marcelo F

    2014-01-01

    Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC) injected into the vitreous body in a model of optic nerve injury. Adult (3-5 months old) Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1? expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime. PMID:25347773

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

    PubMed

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

    2012-07-26

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

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

    PubMed Central

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

    2013-01-01

    The suppressive effect of neural stem cells (NSCs) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), has been reported. However, the migration of NSCs to inflammatory sites was relatively slow as was the onset of rather limited clinical benefit. Lack of, or low expression of particular chemokine receptors on NSCs could be an important factor underlying the slow migration of NSCs. To enhance the therapeutic effect of NSCs, in the present study we transduced bone marrow (BM)-derived NSCs with CCR5, a receptor for CCL3, CCL4, and CCL5, chemokines that are abundantly produced in CNS-inflamed foci of MS/EAE. After i.v. injection, CCR5-NSCs rapidly reached EAE foci in larger numbers, and more effectively suppressed CNS inflammatory infiltration, myelin damage, and clinical EAE than GFP-NSCs used as controls. CCR5-NSC-treated mice also exhibited augmented remyelination and neuron/oligodendrocyte repopulation compared to PBS- or GFP-NSC-treated mice. We inferred that the critical mechanism underlying enhanced effect of CCR5-transduced NSCs on EAE is the early migration of chemokine receptor-transduced NSCs into the inflamed foci. Such migration at an earlier stage of inflammation enables NSCs to exert more effective immunomodulation, to reduce the extent of early myelin/neuron damage by creating a less hostile environment for remyelinating cells, and possibly to participate in the remyelination/neural re-population process. These features of BM-derived transduced NSCs, combined with their easy availability (the subject’s own BM) and autologous properties, may lay the groundwork for an innovative approach to rapid and highly effective MS therapy. PMID:22526024

  16. PBS Online NewsHour: Adult Stem Cells

    NSDL National Science Digital Library

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

  17. Stem cell therapy for autism.

    PubMed

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

    2007-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism. PMID:17597540

  18. Stem Cell Therapy for Autism

    PubMed Central

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

    2007-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism. PMID:17597540

  19. The therapeutic effects of bone marrow mesenchymal stem cells after optic nerve damage in the adult rat

    PubMed Central

    Tan, HaiBo; Kang, Xin; Lu, ShiHeng; Liu, Lin

    2015-01-01

    Optic nerve trauma is a common occurrence that results in irreversible blindness. Currently, no effective strategies are known to prevent optic nerve degeneration. We assessed the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) after optic nerve crush in the adult rat. Our results showed that BMSCs significantly promoted the regeneration of injured axons compared with phosphate buffered saline alone. Therefore, BMSC transplantation may be effective for the treatment of central nervous system disorders. PMID:25733825

  20. The therapeutic effects of bone marrow mesenchymal stem cells after optic nerve damage in the adult rat.

    PubMed

    Tan, HaiBo; Kang, Xin; Lu, ShiHeng; Liu, Lin

    2015-01-01

    Optic nerve trauma is a common occurrence that results in irreversible blindness. Currently, no effective strategies are known to prevent optic nerve degeneration. We assessed the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) after optic nerve crush in the adult rat. Our results showed that BMSCs significantly promoted the regeneration of injured axons compared with phosphate buffered saline alone. Therefore, BMSC transplantation may be effective for the treatment of central nervous system disorders. PMID:25733825

  1. Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

    Microsoft Academic Search

    K Nakamura; Y Ito; Y Kawano; K Kurozumi; M Kobune; H Tsuda; A Bizen; O Honmou; Y Niitsu; H Hamada

    2004-01-01

    The prognosis of patients with malignant glioma is extremely poor, despite the extensive surgical treatment that they receive and recent improvements in adjuvant radio- and chemotherapy. In the present study, we propose the use of gene-modified mesenchymal stem cells (MSCs) as a new tool for gene therapy of malignant brain neoplasms. Primary MSCs isolated from Fischer 344 rats possessed excellent

  2. Effectiveness of Partner Social Support Predicts Enduring Psychological Distress After Hematopoietic Stem Cell Transplantation

    Microsoft Academic Search

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

    2011-01-01

    Objective: Hematopoietic stem cell transplant (HSCT) survivors who are 1 to 3 years posttransplant are challenged by the need to resume valued social roles and activities—a task that may be complicated by enduring transplant-related psychological distress common in this patient population. The present study investigated whether transplant survivors who receive adequate social support from their spouse or intimate partner experience

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

    ERIC Educational Resources Information Center

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

    2011-01-01

    Objective: Hematopoietic stem cell transplant (HSCT) survivors who are 1 to 3 years posttransplant are challenged by the need to resume valued social roles and activities--a task that may be complicated by enduring transplant-related psychological distress common in this patient population. The present study investigated whether transplant…

  4. Effect of uniaxial stretch on morphology and cytoskeleton of human mesenchymal stem cells: static vs. dynamic loading.

    PubMed

    Goli-Malekabadi, Zahra; Tafazzoli-Shadpour, Mohammad; Rabbani, Mohsen; Janmaleki, Mohsen

    2011-10-01

    Abstract Human mesenchymal stem cells (hMSCs) are capable of self-renewal and differentiation into various cell lineages. Mechanical stimuli have been shown to regulate function of stem cells through alteration in morphology and structure. The aim of this study was to evaluate and compare effects of uniaxial static stretch and combined static-dynamic stretch on the orientation, regulation and cytoskeletal structure of hMSCs. Mean values of topological were calculated before and after loadings. Moreover, fractal dimension (FD) was employed to quantify alterations in shape complexity of the cells. Internal cytoskeletal structure of cells was observed by actin filament staining. Results demonstrated a statistically significant change in cell topology and FD due to 10% static-dynamic stretch after 24 h. Static stretch was not as influential as dynamic loading. Whereas for combined static-dynamic stretch systemic alignment of cells was detected, in the static test group local alignment of actin fibers was observed, although the entire cell network was not totally aligned in a specific direction. It was concluded that dynamic stretch leads to cytoskeletal alignment and repolarization of hMSCs, whereas static stretch does not. Under static stretch hMSCs proliferated more than under dynamic stretch. Results can be applied in tissue engineering when functionalization of stem cells is required. PMID:21988158

  5. Issues in-depth : Setting FIRES to stem cell research

    NSDL National Science Digital Library

    Roxanne Greitz Miller

    2005-01-01

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

  6. GPCRs in stem cell function.

    PubMed

    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

  7. 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

  8. In vitro and in vivo expansion of stem cell populations.

    PubMed

    Wagemaker, G

    1998-01-01

    Expansion of hemopoietic stem cells occurs in vivo following transplantation of limited numbers of bone marrow cells or of highly purified stem cells. Stem cell expansion can in principle be achieved in vitro and also be promoted in vivo by growth factor treatment, notably with thrombopoietin. Advances in identification of stromal elements, growth factors and culture conditions that stimulate immature hemopoietic stem cell proliferation may result in effective stem cell expansion protocols and contribute to efficient retrovirally mediated gene transfer. In vivo expansion of immature cells by growth factor treatment may both be a valid alternative and an adjuvant to in vitro expansion. PMID:9704482

  9. Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells

    SciTech Connect

    Hyun, Kyung-Hwan; Yoon, Chang-Hwan; Kim, Rae-Kwon; Lim, Eun-Jung [Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); An, Sungkwan [Functional Genoproteome Research Centre, Konkuk University, Seoul 143-701 (Korea, Republic of); Park, Myung-Jin [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hyun, Jin-Won [College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756 (Korea, Republic of); Suh, Yongjoon [Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Kim, Min-Jung, E-mail: kimmj74@hanyang.ac.kr [Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae, E-mail: sj0420@hanyang.ac.kr [Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2011-07-01

    A subpopulation of cancer cells with stem cell properties is responsible for tumor maintenance and progression, and may contribute to resistance to anticancer treatments. Thus, compounds that target cancer stem-like cells could be usefully applied to destroy cancer. In this study, we investigated the effect of Eckol, a phlorotannin compound, on stemness and malignancies in glioma stem-like cells. To determine whether Eckol targets glioma stem-like cells, we examined whether Eckol treatment could change the expression levels of glioma stem-like cell markers and self-renewal-related proteins as well as the sphere forming ability, and the sensitivity to anticancer treatments. Alterations in the malignant properties of sphere-derived cells by Eckol were also investigated by soft-agar colony forming assay, by xenograft assay in nude mice, and by cell invasion assay. Treatment of sphere-forming glioma cells with Eckol effectively decreased the sphere formation as well as the CD133{sup +} cell population. Eckol treatment suppressed expression of the glioma stem-like cell markers and the self-renewal-related proteins without cell death. Moreover, treatment of glioma stem-like cells with Eckol significantly attenuated anchorage-independent growth on soft agar and tumor formation in xenograft mice. Importantly, Eckol treatment effectively reduced the resistance of glioma stem-like cells to ionizing radiation and temozolomide. Treatment of glioma stem-like cells with Eckol markedly blocked both phosphoinositide 3-kinase-Akt and Ras-Raf-1-Erk signaling pathways. These results indicate that the natural phlorotannin Eckol suppresses stemness and malignancies in glioma stem-like cells, and thereby makes glioma stem-like cells more sensitive to anticancer treatments, providing novel therapeutic strategies targeting specifically cancer stem-like cells.

  10. Bronchoalveolar Sublineage Specification of Pluripotent Stem Cells: Effect of Dexamethasone Plus cAMP-Elevating Agents and Keratinocyte Growth Factor.

    PubMed

    Katsirntaki, Katherina; Mauritz, Christina; Olmer, Ruth; Schmeckebier, Sabrina; Sgodda, Malte; Puppe, Verena; Eggenschwiler, Reto; Duerr, Julia; Schubert, Susanne C; Schmiedl, Andreas; Ochs, Matthias; Cantz, Tobias; Salwig, Isabelle; Szibor, Marten; Braun, Thomas; Rathert, Christian; Martens, Andreas; Mall, Marcus A; Martin, Ulrich

    2015-02-01

    Respiratory progenitors can be efficiently generated from pluripotent stem cells (PSCs). However, further targeted differentiation into bronchoalveolar sublineages is still in its infancy, and distinct specifying effects of key differentiation factors are not well explored. Focusing on airway epithelial Clara cell generation, we analyzed the effect of the glucocorticoid dexamethasone plus cAMP-elevating agents (DCI) on the differentiation of murine embryonic and induced pluripotent stem cells (iPSCs) into bronchoalveolar epithelial lineages, and whether keratinocyte growth factor (KGF) might further influence lineage decisions. We demonstrate that DCI strongly induce expression of the Clara cell marker Clara cell secretory protein (CCSP). While KGF synergistically supports the inducing effect of DCI on alveolar markers with increased expression of surfactant protein (SP)-C and SP-B, an inhibitory effect on CCSP expression was shown. In contrast, neither KGF nor DCI seem to have an inducing effect on ciliated cell markers. Furthermore, the use of iPSCs from transgenic mice with CCSP promoter-dependent lacZ expression or a knockin of a YFP reporter cassette in the CCSP locus enabled detection of derivatives with Clara cell typical features. Collectively, DCI was shown to support bronchoalveolar specification of mouse PSCs, in particular Clara-like cells, and KGF to inhibit bronchial epithelial differentiation. The targeted in vitro generation of Clara cells with their important function in airway protection and regeneration will enable the evaluation of innovative cellular therapies in animal models of lung diseases. PMID:25316003

  11. Effect of vitamin C on growth of caprine spermatogonial stem cells in vitro.

    PubMed

    Wang, Juhua; Cao, Hongguo; Xue, Xiuheng; Fan, Caiyun; Fang, Fugui; Zhou, Jie; Zhang, Yunhai; Zhang, Xiaorong

    2014-03-01

    The genetic manipulation of spermatogonial stem cells (SSCs) can be used for the production of transgenic animals in a wide range of species. However, this technology is limited by the absence of an ideal culture system in which SSCs can be maintained and proliferated, especially in domestic animals like the goat. The aim of this study therefore was to investigate whether the addition of vitamin C (Vc) in cell culture influences the growth of caprine SSCs. Various concentrations of Vc (0, 5, 10, 25, 40, and 50 ?g/mL(-1)) were added to SSC culture media, and their effect on morphology and alkaline phosphatase activity was studied. The number of caprine SSC colonies and area covered by them were measured at 10 days of culture. The expression of various germ cell and somatic cell markers such as VASA, integrins, Oct-4, GATA-4, ?-SMA, vimentin, and Thy-1 was studied to identify the proliferated cells using immunostaining analyses. Further, the intracellular reactive oxygen species (ROS) level was measured at the 3rd, 6th, and 9th day after culture, and expression of Bax, Bcl-2, and P53, factors involved in the regulation of apoptosis, were analyzed on the 7th day after culture using reverse transcription polymerase chain reaction and quantitative real-time polymerase chain reaction. The results showed that the SSCs formed compact colonies and had unclear borders in the different Vc-supplemented groups at 10 days, and there were no major morphologic differences between the groups. The number and area of colonies were both the highest in the 40 ?g/mL(-1) Vc group. Differential expression of markers for germ cells, undifferentiated spermatogonia, and testis somatic cells was observed. Cultured germ cell clumps were found to have alkaline phosphatase activity regardless of the Vc dose. The number of Thy-1- and Oct-4-positive cells was the most in the 40 ?g/mL(-1) Vc group. Moreover, the level of ROS was dependent on the Vc dose and culture time. The Vc dose 40 ?g/mL(-1) was found to be optimum with regard to decreasing ROS generation, and increasing the expression of the antiapoptotic gene Bcl-2 and decreasing the expression of the proapoptotic genes Bax and P53. In conclusion, the addition of 40 ?g/mL(-1) Vc can maintain a certain physiological level of ROS, trigger the expression of the antiapoptosis gene Bcl-2, suppress the proapoptotic gene P53 and Bax pathway, and further promote the proliferation of caprine SSCs in vitro. PMID:24368149

  12. Effect of Labeling with Iron Oxide Particles or Nanodiamonds on the Functionality of Adipose-Derived Mesenchymal Stem Cells

    PubMed Central

    Blaber, Sinead P.; Hill, Cameron J.; Webster, Rebecca A.; Say, Jana M.; Brown, Louise J.; Wang, Shih-Chang; Vesey, Graham; Herbert, Benjamin Ross

    2013-01-01

    Stem cells are increasingly the focus of translational research as well as having emerging roles in human cellular therapy. To support these uses there is a need for improved methods for in vivo cell localization and tracking. In this study, we examined the effects of cell labeling on the in vitro functionality of human adipose-derived mesenchymal stem cells. Our results provide a basis for future in vivo studies investigating implanted cell fate and longevity. In particular, we investigated the effects of two different particles: micron-sized (?0.9 µm) fluorescently labeled (Dragon Green) superparamagnetic iron oxide particles (M-SPIO particles); and, carboxylated nanodiamonds of ?0.25 µm in size. The effects of labeling on the functionality of adipose-derived MSCs were assessed by in vitro morphology, osteogenic and adipogenic differentiation potential, CD marker expression, cytokine secretion profiling and quantitative proteomics of the intra-cellular proteome. The differentiation and CD marker assays for stem-like functionality were not altered upon label incorporation and no secreted or intra-cellular protein changes indicative of stress or toxicity were detected. These in vitro results indicate that the M-SPIO particles and nanodiamonds investigated in this study are biocompatible with MSCs and therefore would be suitable labels for cell localization and tracking in vivo. PMID:23301012

  13. Effect of labeling with iron oxide particles or nanodiamonds on the functionality of adipose-derived mesenchymal stem cells.

    PubMed

    Blaber, Sinead P; Hill, Cameron J; Webster, Rebecca A; Say, Jana M; Brown, Louise J; Wang, Shih-Chang; Vesey, Graham; Herbert, Benjamin Ross

    2013-01-01

    Stem cells are increasingly the focus of translational research as well as having emerging roles in human cellular therapy. To support these uses there is a need for improved methods for in vivo cell localization and tracking. In this study, we examined the effects of cell labeling on the in vitro functionality of human adipose-derived mesenchymal stem cells. Our results provide a basis for future in vivo studies investigating implanted cell fate and longevity. In particular, we investigated the effects of two different particles: micron-sized (~0.9 µm) fluorescently labeled (Dragon Green) superparamagnetic iron oxide particles (M-SPIO particles); and, carboxylated nanodiamonds of ~0.25 µm in size. The effects of labeling on the functionality of adipose-derived MSCs were assessed by in vitro morphology, osteogenic and adipogenic differentiation potential, CD marker expression, cytokine secretion profiling and quantitative proteomics of the intra-cellular proteome. The differentiation and CD marker assays for stem-like functionality were not altered upon label incorporation and no secreted or intra-cellular protein changes indicative of stress or toxicity were detected. These in vitro results indicate that the M-SPIO particles and nanodiamonds investigated in this study are biocompatible with MSCs and therefore would be suitable labels for cell localization and tracking in vivo. PMID:23301012

  14. Effect of preeclampsia on umbilical cord blood stem cells in relation to breast cancer susceptibility in the offspring.

    PubMed

    Qiu, Li; Onoyama, Sagano; Low, Hoi Pang; Chang, Chien-I; Strohsnitter, William C; Norwitz, Errol R; Lopresti, Mary; Edmiston, Kathryn; Lambe, Mats; Trichopoulos, Dimitrios; Lagiou, Pagona; Hsieh, Chung-Cheng

    2015-01-01

    Women born from a preeclamptic (PE) pregnancy are associated with a lower risk of breast cancer. Prenatal and early-life exposures are hypothesized to influence breast cancer susceptibility through their effect on stem cells. We examined stem cell populations in umbilical cord blood from PE pregnancies and compared with those from pregnancies without this condition. We isolated mononuclear cells from 58 PE and 197 normotensive (non-PE) umbilical cord blood samples and examined the different stem cell populations. Hematopoietic (CD34(+) and CD34(+)CD38(-)), endothelial (CD34(+)CD133(+), CD34(+)VEGFR2(+), CD133(+)VEGFR2(+) and CD34(+)CD133(+)VEGFR2(+)), and putative breast (EpCAM(+), EpCAM(+)CD49f(+), EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+), CD24(+)CD29(+) and CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations were quantified by flow cytometry and compared between PE and non-PE samples. Hematopoietic CD34(+) cell counts were significantly lowered in PE compared with non-PE samples (P = 0.039, Kruskal-Wallis test). Levels of CD34(+)CD133(+) endothelial progenitor cells were also lower in PE samples (P = 0.032, multiple regression analysis). EpCAM(+) and EpCAM(+)CD49f(+) putative breast stem cell levels were significantly lowered in PE subjects (multiple regression analysis: P = 0.038 and 0.007, respectively). Stratifying by newborn gender, EpCAM(+) and EpCAM(+)CD49f(+) stem cells were significantly lowered in PE samples of female, but not male, newborns. Umbilical cord blood samples from pregnancies complicated by preeclampsia thus had significantly lower levels of hematopoietic, endothelial, and putative breast stem cells than non-PE controls. With a lowered breast cancer risk for offspring of a PE pregnancy, our findings provide support to the hypothesis that susceptibility to breast oncogenesis may be affected by conditions and processes during the prenatal period. PMID:25398884

  15. HPMA copolymer-based combination therapy toxic to both prostate cancer stem/progenitor cells and differentiated cells induces durable anti-tumor effects

    PubMed Central

    Zhou, Yan; Yang, Jiyuan; Rhim, Johng S.; Kope?ek, Jind?ich

    2013-01-01

    Current treatments for prostate cancer are still not satisfactory, often resulting in tumor regrowth and metastasis. One of the main reasons for the ineffective anti-prostate cancer treatments is the failure to deplete cancer stem-like cells (CSCs) - a subset of cancer cells with enhanced tumorigenic capacity. Thus, combination of agents against both CSCs and bulk tumor cells may offer better therapeutic benefits. Several molecules with anti-cancer stem/progenitor cell activities have been under preclinical evaluations. However, their low solubility and nonspecific toxicity limit their clinical translation. Herein, we designed a combination macromolecular therapy containing two drug conjugates: HPMA copolymer-cyclopamine conjugate (P-CYP) preferentially toxic to cancer stem/progenitor cells, and HPMA copolymer-docetaxel conjugate (P-DTX) effective in debulking the tumor mass. Both conjugates were synthesized using RAFT (reversible addition-fragmentation chain transfer) polymerization resulting in narrow molecular weight distribution. The killing effect of the two conjugates against bulk tumor cells and CSCs were evaluated in vitro and in vivo. In PC-3 or RC-92a/hTERT prostate cancer cells, P-CYP preferentially kills and impairs the function of CD133+ prostate cancer stem/progenitor cells; P-DTX was able to kill bulk tumor cells instead of CSCs. In PC-3 xenograft mice model, combination of P-DTX and P-CYP showed the most effective and persistent tumor growth inhibitory effect. In addition, residual tumors contained less CD133+ cancer cells following combination or P-CYP treatments, indicating selective killing of cancer cells with stem/progenitor cell properties. PMID:24041709

  16. Dose rate effects on the survival of normal hematopoietic stem cells cells of BALB/c mice

    SciTech Connect

    Glasgow, G.P. (Washington Univ. School of Medicine, St. Louis, MO); Beetham, K.L.; Mill, W.B.

    1983-04-01

    The use of total body irradiation (TBI) to ablate malignant stem cells in leukemia patients prior to bone marrow transplantation and the use of hemibody irradiation (HBI) for treating osseous metastases have focused attention on the dose rate effects, if any, exhibited by normal or malignant hematopoietic stem cells. Using male BALB/c mice 10 to 12 weeks old, we investigated dose rate effects at 103, 45 and 8 rad/ min over the dose range from 100 to 500 rad. Bone marrow cells from the femurs of irradiated donor mice were transplanted into lethally irradiated (720 rad) mice of the same age, sex, and strain. Recipient mice were sacrifices 9 days later, their spleens fixed, stained with Bouin's solution, and the macroscopic colonies counted to determine the number of colony forming units (CFU) per femur. Surviving fractions were determined by comparisons to the CFU's of non-treated controls. The logarithms of the surviving fractions, S, versus dose, D, (in rad) were least squares fitted and the extrapolation number, n, and D/sub 0/ obtained. The extrapolation numbers ranged from 0.65+/-0.15 to 0.81, and D/sub 0/ ranged from 61.7+/- 3.4 to 69.0+/- 2.8. There are no statistically significant differences between the n's and /d/sub 0/'s for these different dose rates over the dose range from 100 to 500 rad, as measured by spleen CFU assay of normal femoral marrow. The D's are appropriate for this radiosensitive mouse strain. These data are compared to those from other studies using the same method of CFU assay.

  17. Effects of non-thermal atmospheric plasma on human periodontal ligament mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Mileti?, M.; Mojsilovi?, S.; Oki? ?or?evi?, I.; Maleti?, D.; Pua?, N.; Lazovi?, S.; Malovi?, G.; Milenkovi?, P.; Petrovi?, Z. Lj; Bugarski, D.

    2013-08-01

    Here we investigate the influences of non-thermal atmospheric plasma on human mesenchymal stem cells isolated from periodontal ligament (hPDL-MSCs). A specially redesigned plasma needle was used as the source of low-temperature plasma and its effects on different hPDL-MSC functions were investigated. Cell cultures were obtained from extracted normal impacted third molars and characterized for their phenotype and multi-potential differentiation. The hPDL-MSCs possessed all the typical MSC properties, including clonogenic ability, high proliferation rate, specific phenotype and multilineage differentiation. The data regarding the interaction of plasma with hPDL-MSCs demonstrated that plasma treatment inhibited the migration of hPDL-MSCs and induced some detachment, while not affecting their viability. Additionally, plasma significantly attenuated hPDL-MSCs' proliferation, but promoted their osteogenic differentiation. The results of this study indicated that a non-thermal plasma offers specific activity with non-destructive properties that can be advantageous for future dental applications.

  18. [Effect of umbilical cord MSC infusion on the pulmonary infection in haploidentical hematopoietic stem cell transplantation].

    PubMed

    Han, Dong-Mei; Wang, Zhi-Dong; Ding, Li; Zheng, Xiao-Li; Yan, Hong-Min; Xue, Mei; Zhu, Ling; Liu, Jing; Wang, Heng-Xiang

    2014-08-01

    This study was purposed to investigate the effect of umbilical cord mesenchymal cells (UC-MSC) infusion on the pulmonary infection in haploidentical hematopoietic stem cell transplantation (hi-HSCT). The infection of 83 patients underwent hi-HSCT was detected and analysed, among them 42 patients received haploidentical hi-HSCT, 41 received hi-HSCT combined with UC-MSC infusion. The results showed that 31 cases (73.81% ± 6.78%) were infected by cytomegalovirus and 21 cases in patients received hi-HSCT experienced pulmonary infections, including infections of fungal, virus, bacteria, tubercle bacillus, PCP and so on, the incidence rate was (50 ± 7.72)%; the infection of cytomegalovirus (CMV) was found in 31 cases, the incidence rate was (78.05 ± 6.46)%. In patients received hi-HSCT combined with UC-MSC, only 15 patients experienced pulmonary infection, the incidence rate was (36.59 ± 7.52)%, and the infection of cytomegalovirus (CMV) was observed in 32 patients, the incidence rate was (78.05 ± 6.46)%. There was no obvious statistical difference between two groups(P > 0.05). It is concluded that the UC-MSC infusion not increases the infection rate in hi-HSCT. PMID:25130833

  19. Paracrine Proangiopoietic Effects of Human Umbilical Cord Blood-Derived Purified CD133+ Cells—Implications for Stem Cell Therapies in Regenerative Medicine

    PubMed Central

    Ratajczak, Janina; Kucia, Magda; Mierzejewska, Kasia; Marlicz, Wojciech; Pietrzkowski, Zbigniew; Wojakowski, Wojciech; Greco, Nicholas J.; Tendera, Michal

    2013-01-01

    CD133+ cells purified from hematopoietic tissues are enriched mostly for hematopoietic stem/progenitor cells, but also contain some endothelial progenitor cells and very small embryonic-like stem cells. CD133+ cells, which are akin to CD34+ cells, are a potential source of stem cells in regenerative medicine. However, the lack of convincing donor-derived chimerism in the damaged organs of patients treated with these cells suggests that the improvement in function involves mechanisms other than a direct contribution to the damaged tissues. We hypothesized that CD133+ cells secrete several paracrine factors that play a major role in the positive effects observed after treatment and tested supernatants derived from these cells for the presence of such factors. We observed that CD133+ cells and CD133+ cell-derived microvesicles (MVs) express mRNAs for several antiapoptotic and proangiopoietic factors, including kit ligand, insulin growth factor-1, vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8. These factors were also detected in a CD133+ cell-derived conditioned medium (CM). More important, the CD133+ cell-derived CM and MVs chemoattracted endothelial cells and display proangiopoietic activity both in vitro and in vivo assays. This observation should be taken into consideration when evaluating clinical outcomes from purified CD133+ cell therapies in regenerative medicine. PMID:23003001

  20. Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal stem cells

    PubMed Central

    2014-01-01

    Background Hyperbaric oxygenation was shown to increase bone healing in a rabbit model. However, little is known about the regulatory factors and molecular mechanism involved.We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is mediated via increases in the osteogenic differentiation of mesenchymal stem cells (MSCs) which are regulated by Wnt signaling. Methods The phenotypic characterization of the MSCs was analyzed by flow cytometric analysis. To investigate the effects of HBO on Wnt signaling and osteogenic differentiation of MSCs, mRNA and protein levels of Wnt3a, beta-catenin, GSK-3beta, Runx 2, as well as alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining were analyzed after HBO treatment. To investigate the effects of HBO on Wnt processing and secretion, the expression of Wntless and vacuolar ATPases were quantified after HBO treatment. Results Cells expressed MSC markers such as CD105, CD146, and STRO-1. The mRNA and protein levels of Wnt3a, ?-catenin, and Runx 2 were up-regulated, while GSK-3? was down-regulated after HBO treatment. Western blot analysis showed an increased ?-catenin translocation with a subsequent stimulation of the expression of target genes after HBO treatment. The above observation was confirmed by small interfering (si)RNA treatment. HBO significantly increased alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining of osteogenically differentiated MSCs. We further showed that HBO treatment increased the expression of Wntless, a retromer trafficking protein, and vacuolar ATPases to stimulate Wnt processing and secretion, and the effect was confirmed by siRNA treatment. Conclusions HBO treatment increased osteogenic differentiation of MSCs via regulating Wnt processing, secretion, and signaling. PMID:24568330

  1. EFFECT OF SCAFFOLD MICROARCHITECTURE ON OSTEOGENIC DIFFERENTIATION OF HUMAN MESENCHYMAL STEM CELLS

    PubMed Central

    Kim, Su Hee; Kim, Soo Hyun; Yamaguchi, Tomonori; Masuda, Koichi; Varghese, Shyni

    2015-01-01

    Design of macroporous synthetic grafts that can promote infiltration of cells, their differentiation, and synthesis of bone-specific extracellular matrix is a key determinant for in vivo bone tissue regeneration and repair. In this study, we investigated the effect of the microarchitecture of the scaffold on osteogenic differentiation of human mesenchymal stem cells (hMSCs). Poly(ethylene glycol) diacrylate-co-N-acryloyl 6-aminocaproic acid cryogels were fabricated to have either a pore network consisting of cellular, randomly oriented pores (termed ‘spongy’) or a pore network consisting of lamellar columns (termed ‘columnar’), with both cryogel types showing a similar porosity. Both spongy and columnar cryogels supported comparable levels of cell viability and proliferation of hMSCs in vitro. However, spongy cryogels promoted osteogenic differentiation to a greater extent than their columnar counterparts, as evidenced by increased alkaline phosphatase activity and osteoblastic gene expression over 21 days post culture. Leveraging upon our previous work, we further evaluated the ability of these synthetic scaffolds in conjunction with mineralisation to promote ectopic bone formation upon subcutaneous implantation in nude rats. Mineralised spongy and columnar cryogels, both in the presence and absence of exogenous hMSCs, promoted ectopic bone formation in vivo. No such bone formation was observed in acellular cryogels devoid of mineralisation, with extensive host cell infiltration and vascularisation in columnar cryogels, and negligible infiltration into spongy cryogels. Our results thus present a novel method to tune the microarchitecture of porous polymeric scaffolds, in addition to suggesting their efficacy as synthetic bone grafts. PMID:23329467

  2. Stem cells and cardiac regeneration.

    PubMed

    Kocher, Alfred A; Schlechta, Bernhard; Gasparovicova, Aneta; Wolner, Ernst; Bonaros, Nikolaos; Laufer, Günther

    2007-09-01

    Despite many advances in cardiovascular medicine, heart failure (HF) remains the leading cause of death in developed countries affecting at least 10 million people in Western Europe alone. The poor long-term prognosis of HF patients, and immense public health implications has fuelled interest in finding new therapeutic modalities. Recent observations of the beneficial effect of stem cells on the damaged heart in animal experiments have generated tremendous excitement and stimulated clinical studies suggesting that this approach is feasible, safe, and potentially effective in humans. Cell-based myocardial regeneration is currently explored for a wide range of cardiac disease states, including acute and chronic ischemic myocardial damage, cardiomyopathy and as biological heart pacemakers. The aim of the present manuscript is to review the work that has been done to establish the role of stem cells in cardiac repair, give an update on the clinical trials performed so far, as well as to discuss critically the controversies, challenges and future surrounding this novel therapeutic concept. PMID:17555531

  3. Sources of Stem Cells for Transplant

    MedlinePLUS

    ... Topic Donor matching for allogeneic transplant Sources of stem cells for transplant There are 3 possible sources of ... cord blood transplants are being actively studied. Which stem cell source is best? All 3 sources of stem ...

  4. Ovarian germline stem cells.

    PubMed

    Dunlop, Cheryl E; Telfer, Evelyn E; Anderson, Richard A

    2014-01-01

    It has long been established that germline stem cells (GSCs) are responsible for lifelong gametogenesis in males, and some female invertebrates (for example, Drosophila) and lower vertebrates (for example, teleost fish and some prosimians) also appear to rely on GSCs to replenish their oocyte reserve in adulthood. However, the presence of such cells in the majority of female mammals is controversial, and the idea of a fixed ovarian reserve determined at birth is the prevailing belief among reproductive biologists. However, accumulating evidence demonstrates the isolation and culture of putative GSCs from the ovaries of adult mice and humans. Live offspring have been reportedly produced from the culture of adult mouse GSCs, and human GSCs formed primordial follicles using a mouse xenograft model. If GSCs were present in adult female ovaries, it could be postulated that the occurrence of menopause is not due to the exhaustion of a fixed supply of oocytes but instead is a result of GSC and somatic cell aging. Alternatively, they may be benign under normal physiological conditions. If their existence were confirmed, female GSCs could have many potential applications in both basic science and clinical therapies. GSCs not only may provide a valuable model for germ cell development and maturation but may have a role in the field of fertility preservation, with women potentially being able to store GSCs or GSC-derived oocytes from their own ovaries prior to infertility-inducing treatments. Essential future work in this field will include further independent corroboration of the existence of GSCs in female mammals and the demonstration of the production of mature competent oocytes from GSCs cultured entirely in vitro. PMID:25157949

  5. Role of Oxidative Stress in Stem, Cancer, and Cancer Stem Cells

    PubMed Central

    Dayem, Ahmed Abdal; Choi, Hye-Yeon; Kim, Jung-Hyun; Cho, Ssang-Goo

    2010-01-01

    The term ‘‘oxidative stress” refers to a cell’s state characterized by excessive production of reactive oxygen species (ROS) and oxidative stress is one of the most important regulatory mechanisms for stem, cancer, and cancer stem cells. The concept of cancer stem cells arose from observations of similarities between the self-renewal mechanism of stem cells and that of cancer stem cells, but compared to normal stem cells, they are believed to have no control over the cell number. ROS have been implicated in diverse processes in various cancers, and generally the increase of ROS in cancer cells is known to play an important role in the initiation and progression of cancer. Additionally, ROS have been considered as the most significant mutagens in stem cells; when elevated, blocking self-renewal and at the same time, serving as a signal stimulating stem cell differentiation. Several signaling pathways enhanced by oxidative stress are suggested to have important roles in tumorigenesis of cancer or cancer stem cells and the self-renewal ability of stem or cancer stem cells. It is now well established that mitochondria play a prominent role in apoptosis and increasing evidence supports that apoptosis and autophagy are physiological phenomena closely linked with oxidative stress. This review elucidates the effect and the mechanism of the oxidative stress on the regulation of stem, cancer, and cancer stem cells and focuses on the cell signaling cascades stimulated by oxidative stress and their mechanism in cancer stem cell formation, as very little is known about the redox status in cancer stem cells. Moreover, we explain the link between ROS and both of apoptosis and autophagy and the impact on cancer development and treatment. Better understanding of this intricate link may shed light on mechanisms that lead to better modes of cancer treatment. PMID:24281098

  6. UCLA stem cell scientists discover new airway stem cell:

    Cancer.gov

    Researchers at UCLA have identified a new stem cell that participates in the repair of the large airways of the lungs, which play a vital role in protecting the body from infectious agents and toxins in the environment.

  7. Cell Stem Cell Stage-Specific Differences in the

    E-print Network

    Hay, Bruce A.

    Cell Stem Cell Article Stage-Specific Differences in the Requirements for Germline Stem CellDepartment of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington tissues in the animal kingdom depend on stem cell populations. Embryonic stem cells are considered

  8. Planarian Regeneration and Stem Cells

    NSDL National Science Digital Library

    Alejandro Sánchez Alvarado (Howard Hughes Medical Institute; )

    2007-03-31

    A mini-documentary discussing the remarkable regenerative capabilities of the planarian, and how HHMI researcher Alejandro Snchez Alvarado uses them to study the biology of stem cells. This presentation is also featured on the DVD Potent Biology: Stem Cells, Cloning, and Regeneration, available for free from HHMI. This video is 11 minutes and 46 seconds in length, and available for download in Quicktime (114 MB) and Windows Media (156 MB) formats. All Stem Cell videos are located at: http://www.hhmi.org/biointeractive/stemcells/video.html.

  9. Cancer Stem Cells and Differentiation Therapy

    Microsoft Academic Search

    Stewart Sell

    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

  10. Effects of Combinatorial Treatment with Pituitary Adenylate Cyclase Activating Peptide and Human Mesenchymal Stem Cells on Spinal Cord Tissue Repair

    Microsoft Academic Search

    Kuan-Min Fang; Jen-Kun Chen; Shih-Chieh Hung; Mei-Chun Chen; Yi-Ting Wu; Tsung-Jung Wu; Hsin-I. Lin; Chia-Hua Chen; Henrich Cheng; Chung-Shi Yang; Shun-Fen Tzeng; Dimas Tadeu Covas

    2010-01-01

    The aim of this study is to understand if human mesenchymal stem cells (hMSCs) and neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) have synergistic protective effect that promotes functional recovery in rats with severe spinal cord injury (SCI). To evaluate the effect of delayed combinatorial therapy of PACAP and hMSCs on spinal cord tissue repair, we used the immortalized hMSCs that

  11. Non-thermal effects of terahertz radiation on gene expression in mouse stem cells

    PubMed Central

    Alexandrov, Boian S.; Rasmussen, Kim Ř.; Bishop, Alan R.; Usheva, Anny; Alexandrov, Ludmil B.; Chong, Shou; Dagon, Yossi; Booshehri, Layla G.; Mielke, Charles H.; Phipps, M. Lisa; Martinez, Jennifer S.; Chen, Hou-Tong; Rodriguez, George

    2011-01-01

    Abstract In recent years, terahertz radiation sources are increasingly being exploited in military and civil applications. However, only a few studies have so far been conducted to examine the biological effects associated with terahertz radiation. In this study, we evaluated the cellular response of mesenchymal mouse stem cells exposed to THz radiation. We apply low-power radiation from both a pulsed broad-band (centered at 10 THz) source and from a CW laser (2.52 THz) source. Modeling, empirical characterization, and monitoring techniques were applied to minimize the impact of radiation-induced increases in temperature. qRT-PCR was used to evaluate changes in the transcriptional activity of selected hyperthermic genes. We found that temperature increases were minimal, and that the differential expression of the investigated heat shock proteins (HSP105, HSP90, and CPR) was unaffected, while the expression of certain other genes (Adiponectin, GLUT4, and PPARG) showed clear effects of the THz irradiation after prolonged, broad-band exposure. PMID:21991556

  12. Effects of infrasound on the growth of bone marrow mesenchymal stem cells: a pilot study.

    PubMed

    He, Renhong; Fan, Jianzhong

    2014-11-01

    Poor viability of transplanted bone marrow mesenchymal stem cells (BMSCs) is well?known, but developing methods for enhancing the viability of BMSCs requires further investigation. The aim of the present study was to elucidate the effects of infrasound on the proliferation and apoptosis of BMSCs, and to determine the association between survivin expression levels and infrasound on BMSCs. Primary BMSCs were derived from Sprague Dawley rats. The BMSCs, used at passage three, were divided into groups that received infrasound for 10, 30, 60, 90 or 120 min, and control groups, which were exposed to the air for the same durations. Infrasound was found to promote proliferation and inhibit apoptosis in BMSCs. The results indicated that 60 min was the most suitable duration for applied infrasound treatment to BMSCs. The protein and mRNA expression levels of survivin in BMSCs from the two treatment groups that received 60 min infrasound or air, were examined by immunofluorescence and quantitative polymerase chain reaction. Significant differences in survivin expression levels were identified between the two groups, as infrasound enhanced the expression levels of survivin. In conclusion, infrasound promoted proliferation and inhibited apoptosis in BMSCs, and one mechanisms responsible for the protective effects may be the increased expression levels of survivin. PMID:25175368

  13. Inhibition of Nuclear Nox4 Activity by Plumbagin: Effect on Proliferative Capacity in Human Amniotic Stem Cells

    PubMed Central

    Guida, Marianna; Maraldi, Tullia; Resca, Elisa; Beretti, Francesca; Zavatti, Manuela; Bertoni, Laura; La Sala, Giovanni B.; De Pol, Anto

    2013-01-01

    Human amniotic fluid stem cells (AFSC) with multilineage differentiation potential are novel source for cell therapy. However, in vitro expansion leads to senescence affecting differentiation and proliferative capacities. Reactive oxygen species (ROS) have been involved in the regulation of stem cell pluripotency, proliferation, and differentiation. Redox-regulated signal transduction is coordinated by spatially controlled production of ROS within subcellular compartments. NAD(P)H oxidase family, in particular Nox4, has been known to produce ROS in the nucleus; however, the mechanisms and the meaning of this function remain largely unknown. In the present study, we show that Nox4 nuclear expression (nNox4) increases during culture passages up to cell cycle arrest and the serum starvation causes the same effect. With the decrease of Nox4 activity, obtained with plumbagin, a decline of nuclear ROS production and of DNA damage occurs. Moreover, plumbagin exposure reduces the binding between nNox4 and nucleoskeleton components, as Matrin 3. The same effect was observed also for the binding with phospho-ERK, although nuclear ERK and P-ERK are unchanged. Taken together, we suggest that nNox4 regulation may have important pathophysiologic effects in stem cell proliferation through modulation of nuclear signaling and DNA damage. PMID:24489986

  14. Effects of the conditioned medium of mesenchymal stem cells on mouse oocyte activation and development.

    PubMed

    Feng, D Q; Zhou, Y; Ling, B; Gao, T; Shi, Y Y; Wei, H M; Tian, Z G

    2009-06-01

    Mesenchymal stem cells (MSCs) have been reported to secrete a variety of cytokines and growth factors acting as trophic suppliers, but little is known regarding the effects of conditioned medium (CM) of MSCs isolated from femurs and tibias of mouse on the artificial activation of mouse oocytes and on the developmental competence of the parthenotes. In the current study, we investigated the effect of CM on the events of mouse oocyte activation, namely oscillations of cytosolic calcium concentration ([Ca(2)+]i), meiosis resumption, pronucleus formation, and parthenogenetic development. The surface markers of MSCs were identified with a fluorescence-activated cell sorter. The dynamic changes of the spindle and formation of pronuclei were examined by laser-scanning confocal microscopy. Exposure of cumulus-oocyte complexes to CM for 40 min was optimal for inducing oocyte parthenogenetic activation and evoking [Ca(2)+]i oscillations similar to those evoked by sperm (95 vs 100%; P > 0.05). Parthenogenetically activated oocytes immediately treated with 7.5 microg/mL cytochalasin B (CB), which inhibited spindle rotation and second polar body extrusion, were mostly diploid (93 vs 6%, P < 0.01) while CB-untreated oocytes were mostly haploid (5 vs 83%, P < 0.01). Consequently, the blastocyst rate was higher in the CB-treated than in the CB-untreated oocytes. There was no significant difference in developmental rate between oocytes activated with CM and 7% ethanol (62 vs 62%, P > 0.05), but the developmental competence of the fertilized oocytes was superior to that of the parthenotes (88 vs 62%, P < 0.05). The present results demonstrate that CM can effectively activate mouse oocytes, as judged by the generation of [Ca(2)+]i oscillations, completion of meiosis and parthenogenetic development. PMID:19448898

  15. Advances in stem cell therapy for spinal cord injury

    PubMed Central

    Mothe, Andrea J.; Tator, Charles H.

    2012-01-01

    Spinal cord injury (SCI) is a devastating condition producing great personal and societal costs and for which there is no effective treatment. Stem cell transplantation is a promising therapeutic strategy, though much preclinical and clinical research work remains. Here, we briefly describe SCI epidemiology, pathophysiology, and experimental and clinical stem cell strategies. Research in stem cell biology and cell reprogramming is rapidly advancing, with the hope of moving stem cell therapy closer to helping people with SCI. We examine issues important for clinical translation and provide a commentary on recent developments, including termination of the first human embryonic stem cell transplantation trial in human SCI. PMID:23114605

  16. Effects of Vitamin A on In Vitro Maturation of Pre-Pubertal Mouse Spermatogonial Stem Cells

    PubMed Central

    Travers, Albanne; Arkoun, Brahim; Safsaf, Athmane; Milazzo, Jean-Pierre; Absyte, Anne; Bironneau, Amandine; Perdrix, Anne; Sibert, Louis; Macé, Bertrand; Cauliez, Bruno; Rives, Nathalie

    2013-01-01

    Testicular tissue cryopreservation is the only potential option for fertility preservation in pre-pubertal boys exposed to gonadotoxic treatment. Completion of spermatogenesis after in vitro maturation is one of the future uses of harvested testicular tissue. The purpose of the current study was to evaluate the effects of vitamin A on in vitro maturation of fresh and frozen-thawed mouse pre-pubertal spermatogonial stem cells in an organ culture system. Pre-pubertal CD1 mouse fresh testes were cultured for 7 (D7), 9 (D9) and 11 (D11) days using an organ culture system. Basal medium was supplemented with different concentrations of retinol (Re) or retinoic acid (RA) alone or in combination. Seminiferous tubule morphology (tubule diameter, intra-tubular cell type), intra-tubular cell death and proliferation (PCNA antibody) and testosterone level were assessed at D7, D9 and D11. Pre-pubertal mouse testicular tissue were frozen after a soaking temperature performed at -7°C, -8°C or -9°C and after thawing, were cultured for 9 days, using the culture medium preserving the best fresh tissue functionality. Retinoic acid at 10-6M and retinol at 3.3.10-7M, as well as retinol 10-6M are favourable for seminiferous tubule growth, maintenance of intra-tubular cell proliferation and germ cell differentiation of fresh pre-pubertal mouse spermatogonia. Structural and functional integrity of frozen-thawed testicular tissue appeared to be well-preserved after soaking temperature at -8°C, after 9 days of organotypic culture using 10-6M retinol. RA and Re can control in vitro germ cell proliferation and differentiation. Re at a concentration of 10-6M maintains intra-tubular cell proliferation and the ability of spermatogonia to initiate spermatogenesis in fresh and frozen pre-pubertal mouse testicular tissue using a soaking temperature at -8°C. Our data suggested a possible human application for in vitro maturation of cryopreserved pre-pubertal testicular tissue. PMID:24349372

  17. Cancer stem cells in surgery

    PubMed Central

    D’ANDREA, V.; GUARINO, S.; DI MATTEO, F.M.; SACCŔ, M. MAUGERI; DE MARIA, R.

    2014-01-01

    The Cancer Stem Cells (CSC) hypothesis is based on three fundamental ideas: 1) the similarities in the mechanisms that regulate self-renewal of normal stem cells and cancer cells; 2) the possibility that tumour cells might arise from normal stem cells; 3) the notion that tumours might contain ‘cancer stem cells’ - rare cells with indefinite proliferative potential that drive the formation and growth of tumours. The roles for cancer stem cells have been demonstrated for some cancers, such as cancers of the hematopoietic system, breast, brain, prostate, pancreas and liver. The attractive idea about cancer stem cell hypothesis is that it could partially explain the concept of minimal residual disease. After surgical macroscopically zero residual (R0) resections, even the persistence of one single cell nestling in one of the so called “CSCs niches” could give rise to distant relapse. Furthermore the metastatic cells can remain in a “dormant status” and give rise to disease after long period of apparent disease free. These cells in many cases have acquired resistance traits to chemo and radiotherapy making adjuvant treatment vain. Clarifying the role of the cancer stem cells and their implications in the oncogenesis will play an important role in the management of cancer patient by identifying new prospective for drugs and specific markers to prevent and monitoring relapse and metastasis. The identification of the niche where the CSCs reside in a dormant status might represent a valid instrument to follow-up patients also after having obtained a R0 surgical resection. What we believe is that if new diagnostic instruments were developed specifically to identify the localization and status of activity of the CSCs during tumor dormancy, this would lead to impressive improvement in the early detection and management of relapse and metastasis. PMID:25644725

  18. Cancer stem cells in surgery.

    PubMed

    D'Andrea, V; Guarino, S; Di Matteo, F M; Maugeri Saccŕ, M; De Maria, R

    2014-01-01

    The Cancer Stem Cells (CSC) hypothesis is based on three fundamental ideas: 1) the similarities in the mechanisms that regulate self-renewal of normal stem cells and cancer cells; 2) the possibility that tumour cells might arise from normal stem cells; 3) the notion that tumours might contain 'cancer stem cells' - rare cells with indefinite proliferative potential that drive the formation and growth of tumours. The roles for cancer stem cells have been demonstrated for some cancers, such as cancers of the hematopoietic system, breast, brain, prostate, pancreas and liver. The attractive idea about cancer stem cell hypothesis is that it could partially explain the concept of minimal residual disease. After surgical macroscopically zero residual (R0) resections, even the persistence of one single cell nestling in one of the so called "CSCs niches" could give rise to distant relapse. Furthermore the metastatic cells can remain in a "dormant status" and give rise to disease after long period of apparent disease free. These cells in many cases have acquired resistance traits to chemo and radiotherapy making adjuvant treatment vain. Clarifying the role of the cancer stem cells and their implications in the oncogenesis will play an important role in the management of cancer patient by identifying new prospective for drugs and specific markers to prevent and monitoring relapse and metastasis. The identification of the niche where the CSCs reside in a dormant status might represent a valid instrument to follow-up patients also after having obtained a R0 surgical resection. What we believe is that if new diagnostic instruments were developed specifically to identify the localization and status of activity of the CSCs during tumor dormancy, this would lead to impressive improvement in the early detection and management of relapse and metastasis. PMID:25644725

  19. Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

    PubMed Central

    Scintu, Franca; Reali, Camilla; Pillai, Rita; Badiali, Manuela; Sanna, Maria Adele; Argiolu, Francesca; Ristaldi, Maria Serafina; Sogos, Valeria

    2006-01-01

    Background It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. Results In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC). Cells were treated with: (1) TPA, forskolin, IBMX, FGF-1 or (2) retinoic acid and 2-mercaptoethanol (BME). Treatment (1) induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1) compared with treatment (2). In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. Conclusion Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage. PMID:16483379

  20. Renal Stem Cells and Kidney Regeneration

    Microsoft Academic Search

    Takashi Yokoo; Akira Fukui; Kei Matsumoto; Tetsuya Kawamura

    \\u000a Significant advances have been made in stem cell research over the past decade. A number of non-hematopoietic sources of stem\\u000a cells (or progenitor cells) have been identified including endothelial stem cells and neural stem cells. These discoveries\\u000a have been a major step towards the potential regeneration of organs for clinical applications using stem cells. The worldwide\\u000a shortage of donor kidneys

  1. Therapeutic effects of stem cells and substrate reduction in juvenile Sandhoff mice.

    PubMed

    Arthur, J R; Lee, J P; Snyder, E Y; Seyfried, T N

    2012-06-01

    Sandhoff Disease (SD) involves the CNS accumulation of ganglioside GM2 and asialo-GM2 (GA2) due to inherited defects in the ?-subunit gene of ?-hexosaminidase A and B (Hexb gene). Substrate reduction therapy, utilizing imino sugar N-butyldeoxygalactonojirimycin (NB-DGJ), reduces ganglioside biosynthesis and levels of stored GM2 in SD mice. Intracranial transplantation of Neural Stem Cells (NSCs) can provide enzymatic cross correction, to help reduce ganglioside storage and extend life. Here we tested the effect of NSCs and NB-DGJ, alone and together, on brain ?-hexosaminidase activity, GM2, and GA2 content in juvenile SD mice. The SD mice received either cerebral NSC transplantation at post-natal day 0 (p-0), intraperitoneal injection of NB-DGJ (500 mg/kg/day) from p-9 to p-15, or received dual treatments. The brains were analyzed at p-15. ?-galactosidase staining confirmed engraftment of lacZ-expressing NSCs in the cerebral cortex. Compared to untreated and sham-treated SD controls, NSC treatment alone provided a slight increase in Hex activity and significantly decreased GA2 content. However, NSCs had no effect on GM2 content when analyzed at p-15. NB-DGJ alone had no effect on Hex activity, but significantly reduced GM2 and GA2 content. Hex activity was slightly elevated in the NSC + drug-treated mice. GM2 and GA2 content in the dual treated mice were similar to that of the NB-DGJ treated mice. These data indicate that NB-DGJ alone was more effective in targeting storage in juvenile SD mice than were NSCs alone. No additive or synergistic effect between NSC and drug was found in these juvenile SD mice. PMID:22367451

  2. Mesenchymal Stem Cells and Tooth Engineering

    PubMed Central

    Peng, Li; Ye, Ling; Zhou, Xue-dong

    2009-01-01

    Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration. PMID:20690498

  3. Effect of fibroblast growth factor 9 on the osteogenic differentiation of bone marrow stromal stem cells and dental pulp stem cells

    PubMed Central

    LU, JINGTING; DAI, JIEWEN; WANG, XUDONG; ZHANG, MAOLIN; ZHANG, PENG; SUN, HAO; ZHANG, XIULI; YU, HONGBO; ZHANG, WENBIN; ZHANG, LEI; JIANG, XINQUAN; SHEN, STEVE GUOFANG

    2015-01-01

    The role of fibroblast growth factor 9 (FGF9) in bone formation may depend on gene dosage, developmental stage, cell type or interactions with other cytokines. In the present study bone marrow stromal stem cells (BMSCs) and dental pulp stem cells (DPSCs) were cultured and osteogenically induced in vitro, treated with exogenous FGF9 at varying concentrations. Alkaline phosphatase staining, alizarin red S staining, reverse transcription quantitative polymerase chain reaction and western blot analyses were performed in order to investigate the gene expression levels of osteogenic markers. The results of the present study demonstrated that FGF9 enhanced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) during osteogenic induction in BMSCs and DPSCs, which are derived from different tissues. FGF9 also inhibited the osteogenic differentiation of BMSCs and DPSCs through the activation of ERK1/2. These findings suggested that FGF9 may be an inhibitor of osteogenesis in mesenchymal stem cells in vitro and its application in vivo requires investigation in the future. PMID:25435023

  4. Effect of fibroblast growth factor 9 on the osteogenic differentiation of bone marrow stromal stem cells and dental pulp stem cells.

    PubMed

    Lu, Jingting; Dai, Jiewen; Wang, Xudong; Zhang, Maolin; Zhang, Peng; Sun, Hao; Zhang, Xiuli; Yu, Hongbo; Zhang, Wenbin; Zhang, Lei; Jiang, Xinquan; Shen, Steve Guofang

    2015-03-01

    The role of fibroblast growth factor 9 (FGF9) in bone formation may depend on gene dosage, developmental stage, cell type or interactions with other cytokines. In the present study bone marrow stromal stem cells (BMSCs) and dental pulp stem cells (DPSCs) were cultured and osteogenically induced in vitro, treated with exogenous FGF9 at varying concentrations. Alkaline phosphatase staining, alizarin red S staining, reverse transcription quantitative polymerase chain reaction and western blot analyses were performed in order to investigate the gene expression levels of osteogenic markers. The results of the present study demonstrated that FGF9 enhanced the phosphorylation of extracellular signal?regulated kinase 1/2 (ERK1/2) during osteogenic induction in BMSCs and DPSCs, which are derived from different tissues. FGF9 also inhibited the osteogenic differentiation of BMSCs and DPSCs through the activation of ERK1/2. These findings suggested that FGF9 may be an inhibitor of osteogenesis in mesenchymal stem cells in vitro and its application in vivo requires investigation in the future. PMID:25435023

  5. Cell Stem Cell Molecular Pathway and Cell State Responsible

    E-print Network

    South Bohemia, University of

    Cell Stem Cell Article Molecular Pathway and Cell State Responsible for Dissociation-Induced Apoptosis in Human Pluripotent Stem Cells Masatoshi Ohgushi,1,2 Michiru Matsumura,1,2 Mototsugu Eiraku,1 Sasai1,2,* 1Organogenesis and Neurogenesis Group 2Division of Human Stem Cell Technology 3Laboratory

  6. What Is a Stem Cell Niche?

    Microsoft Academic Search

    S. Nishikawa; M. Osawa

    Niche has become the most important issue in stem cell biology, but it is still a hypothetical notion that cannot be defined in a better way than the microenvironment surrounding stem cells. Using a melanocyte stem cell system as a model, we have analyzed the cellular and molecular requirements for differentiation of quiescent stem cells. Our results demonstrate the multiple

  7. Stem Cell Migration in Health and Disease

    Microsoft Academic Search

    Thomas Dittmar; Susannah H. Kassmer; Benjamin Kasenda; Jeanette Seidel; Bernd Niggemann; Kurt S. Zänker

    2010-01-01

    Within the past years, our knowledge about stem cells in health and disease has changed dramatically. To date, it is feasible to isolate and propagate human pluripotent stem cells from various sources, such as cord blood, bone marrow or adipose tissue, and to generate donor-specific ethically harmless induced pluripotent stem cells, which exhibits embryonic stem cell properties. However, irrespective of

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

    PubMed

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

    2014-08-01

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

  9. Cell Stem Cell Wnts as Self-Renewal Factors

    E-print Network

    Verheyen, Esther M.

    Cell Stem Cell Previews Wnts as Self-Renewal Factors: Mammary Stem Cells and Beyond Esther M, Burnaby, British Columbia V5A 1S6, Canada 2Hubrecht Institute for Developmental Biology and Stem Cell.clevers@hubrecht.eu DOI 10.1016/j.stem.2010.05.004 Adult stem cells hold great promise for regenerative medicine, yet

  10. Cancer Stem Cells and Microenvironment

    Microsoft Academic Search

    Mario Federico; Antonio Giordano

    \\u000a The theory of the cancer stem cell (CSC) is fairly recent and has both challenged and disrupted the previous understandings\\u000a of cancer biology. From the initial findings of cancer-driving cellular sub-populations, the interest in the CSC theory has\\u000a flourished. Here we discuss the biology behind both embryonic and adult stem cells and how this biology is the basis for our

  11. Stem Cells Promises to Keep?

    NSDL National Science Digital Library

    Lauren E. Yaich

    2002-01-01

    Samantha and her husband Brad have two children, conceived with the help of in vitro fertilization treatments. After viewing a TV program on stem cells and their potential medical uses, Samantha is convinced that they should donate the remaining frozen embryos they have to medical research, an idea Brad strongly objects to. The case teaches about stem cells and their medical applications as well as the ethical dilemmas posed by their use.

  12. Effect of CNT on collagen fiber structure, stiffness assembly kinetics and stem cell differentiation.

    PubMed

    Kim, Taeyoung; Sridharan, Indumathi; Zhu, Bofan; Orgel, Joseph; Wang, Rong

    2015-04-01

    Collagen is a native one-dimensional nanomaterial. Carbon nanotube (CNT) was found to interface with biological materials and show promising applications in creating reinforced scaffolds for tissue engineering and regenerative medicine. In this study, we examined the unique role of CNT in collagen fiber structure, mechanical strength and assembly kinetics. The results imply that CNT interacts with collagen at the molecular level. It relaxes the helical coil of collagen fibrils and has the effect of flattening the fibers leading to the elongation of D-period, the characteristic banding feature of collagen fibers. The surface charge of oxidized CNT leads to enhanced local ionic strength during collagen fibrillogenesis, accounting for the slower kinetics of collagen-CNT (COL-CNT) fiber assembly and the formation of thicker fibers. Due to the rigidity of CNT, the addition of CNT increases the fiber stiffness significantly. When applied as a matrix for human decidua parietalis placental stem cells (hdpPSCs) differentiation, COL-CNT was found to support fast and efficient neural differentiation ascribed to the elongated D-period. These results highlight the superiority of CNT to modulate collagen fiber assembly at the molecular level. The study also exemplifies the use of CNT to enhance the functionality of collagen for biological and biomedical applications. PMID:25686951

  13. Programmable Mechanobioreactor for Exploration of the Effects of Periodic Vibratory Stimulus on Mesenchymal Stem Cell Differentiation

    PubMed Central

    Cashion, Avery T.; Caballero, Montserrat; Halevi, Alexandra; Pappa, Andrew; Dennis, Robert G.

    2014-01-01

    Abstract A programmable bioreactor using a voice-coil actuator was developed to enable research on the effects of periodic vibratory stimulus on human and porcine mesenchymal stem cells (MSCs). We hypothesized that low frequency vibrations would result in a cartilage phenotype and higher frequency vibrations would result in a bone phenotype. The mechanical stimulation protocol is adjusted from a computer external to the incubator via a USB cable. Once programmed, the embedded microprocessor and sensor system on the bioreactor execute the protocol independent of the computer. In each test, a sinusoidal stimulus was applied to a culture plate in 1-min intervals with a 15-min rest following each, for a total of 15?h per day for 10 days. Frequencies of 1 and 100?Hz were applied to cultures of both human and porcine umbilical cord–derived MSCs. Chondrogenesis was determined by Alcian blue staining for glycosaminoglycans and an increased differentiation index (ratio of mRNA for collagen II and collagen I). Osteogenic differentiation was indicated with Alizarin red for calcium staining and increased bone morphogenetic protein 2 mRNA. One-hertz stimulation resulted in a cartilage phenotype for both human and porcine MSCs, while 100-Hz stimulation resulted in a bone phenotype. PMID:24570842

  14. Human mesenchymal stem cells as delivery of osteoprotegerin gene: homing and therapeutic effect for osteosarcoma

    PubMed Central

    Qiao, Bo; Shui, Wei; Cai, Li; Guo, Shuquan; Jiang, Dianming

    2015-01-01

    Biological treatments have been studied extensively and previous studies have proved that osteoprotegerin (OPG) can inhibit the development and progress of human osteosarcoma. However, the utility of biologic agents for cancer therapy has a short half-life, which can hardly deliver to and function in tumor sites efficiently. Mesenchymal stem cells (MSCs) have the potential to migrate to tumor sites. In this study, MSCs transfected with adenoviruses carrying the OPG gene (MSCs-OPG) were used via the tail vein to treat athymic nude mice (nu/nu) bearing osteosarcoma. In vivo and ex vivo images were used to validate the MSCs homing to tumors. The therapeutic effect for osteosarcoma was evaluated by observations on growth of tumors and bone destruction. The results showed that infected MSCs-OPG labeled with red fluorescent protein (RFP) can migrate to tumor sites and express OPG protein. The treatment by MSCs-OPG reduced the tumor growth and inhibited bone destruction in vivo. All these indicated that MSCs can deliver OPG to tumor sites, which could be a new direction of biological treatment for human osteosarcoma. PMID:25733814

  15. Columbia Stem Cell Initiative Tapping the potential of stem cells for human health

    E-print Network

    Adams, Mark

    Columbia Stem Cell Initiative Tapping the potential of stem cells for human health Tenure Track Faculty Positions in Stem Cell Research at Columbia University Medical Center The Columbia Stem Cell Initiative (CSCI; www.ColumbiaStemCell.org) brings together more than 120 groups working to tap the potential

  16. Curr Gene Ther . Author manuscript Embryonic stem cells or induced pluripotent stem cells? A DNA integrity

    E-print Network

    Paris-Sud XI, Université de

    Curr Gene Ther . Author manuscript Page /1 7 Embryonic stem cells or induced pluripotent stem cells should be addressed to: John De Vos Abstract Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical

  17. Stem Cells of Mammalian Brain: Biology of the Stem Cells in vivoand in vitro

    Microsoft Academic Search

    I. V. Viktorov

    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

  18. The Effects of Alcohol on the Regulation of Imprinted Genes in Mouse Embryonic Stem Cells

    E-print Network

    Villanueva, Elizabeth Mary

    2013-02-04

    RNA, also known as AI747191 Fetal Alcohol Syndrome Disorder Base pair Embryonic Stem Cells Copy DNA 6 CHAPTER I INTRODUCTION Background Our environment plays a huge role in our development. In recent years epigenetics has become a topic..., and other symptoms? [10]. Igf2 is also associated with Russell- Silver syndrome, several cancers, and eating and weight disorders [8]. Ube3a when altered causes Angelman syndrome which is a ?neuro-genetic disorder that . . . causes developmental delay...

  19. [Stem cell factor production from cultured nasal epithelial cells--effect on SCF production by drugs].

    PubMed

    Koyama, Mamoru; Otsuka, Hirokuni; Kusumi, Taeko; Yamauchi, Yoko

    2002-02-01

    We studied whether epithelial cells cultured in serum-free medium contained other cells or not, there were differences in SCF production from cultured nasal epithelial cells between groups of nonallergic and allergic patients, and among degrees of serum mite-CAP RAST classes of allergic patients, and how drugs inhibited SCF production. As a result, no other contaminating cells except mast cell existed in cultured cells. There was a significant difference in SCF production of cultured cells between nonallergic and class 1-2, 3-4, 5-6, and between class 1-2 and 3-4, 5-6 of mite CAP-RAST class. Cyclosporin, prednisolone, fluticasone, ketotifen, and clemastine inhibited SCF production from cultured epithelial cells, but cromoglicate and suplatast did not. Inhibition means the reduction of SCF from cells, not the growth of cultured nasal epithelial cells. PMID:11905054

  20. Evaluation of a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay (SOT)

    EPA Science Inventory

    The Embryonic Stem Cell Test (EST) has been used to evaluate the effects of xenobiotics using three endpoints, stem cell differentiation, stem cell viability and 3T3-cell viability. Our research goal is to establish amodel system that would evaluate chemical effects using a singl...

  1. Migration of bone marrow stem cells in ischaemic brain

    Microsoft Academic Search

    W. S. Poon; G. Lu; K. S. Tsang; X. L. Zhu; G. G. Chen; H. K. Ng

    Stem cell therapy has been demonstrated to be effective in the management of haematological malignancy and solid cancer, but its role in neurodegenerative conditions remains uncertain. We hypothesize that: (1) ventricular delivery of bone marrow stem cells improves functional outcome in experimental ischaemia of the mouse brain; and (2) this improved outcome is due to migration of bone marrow stem

  2. Epigenetic memory in induced pluripotent stem cells

    PubMed Central

    Kim, K; Doi, A; Wen, B; Ng, K; Zhao, R; Cahan, P; Kim, J; Aryee, MJ; Ji, H; Ehrlich, L; Yabuuchi, A; Takeuchi, A; Cunniff, KC; Hongguang, H; Mckinney-Freeman, S; Naveiras, O; Yoon, TJ; Irizarry, RA; Jung, N; Seita, J; Hanna, J; Murakami, P; Jaenisch, R; Weissleder, R; Orkin, SH; Weissman, IL; Feinberg, AP; Daley, GQ

    2011-01-01

    Summary Somatic cell nuclear transfer and transcription factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. These two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, by different mechanisms and kinetics, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low passage induced pluripotent stem cells (iPSC) derived by factor-based reprogramming harbor residual DNA methylation signatures characteristic of their somatic tissue of origin, which favors their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an “epigenetic memory” of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSC with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSC, consistent with more effective reprogramming. Our data demonstrate that factor-based reprogramming can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modeling or treatment. PMID:20644535

  3. Types of Stem Cell Transplants for Treating Cancer

    MedlinePLUS

    ... Sources of stem cells for transplant Types of stem cell transplants for treating cancer In a typical stem ... come from your identical twin or triplet Autologous stem cell transplants These stem cells come from you alone. ...

  4. Future Research in Adipose Stem Cell Engineering

    Microsoft Academic Search

    Jeanne Adiwinata Pawitan

    \\u000a Adipose stem cells have a bright prospect in regenerative medicine for tissue\\/organ engineering. However, some hurdles may\\u000a hinder the progress of adipose stem cell engineering. Therefore this chapter highlights the advances in adipose stem cell\\u000a researches, and focuses on prospective researches that are needed to overcome the hurdles in adipose stem cell engineering,\\u000a i.e., to identify the various stem cells

  5. 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. PMID:22329581

  6. Cell surface engineering of mesenchymal stem cells.

    PubMed

    Sarkar, Debanjan; Zhao, Weian; Gupta, Ashish; Loh, Wei Li; Karnik, Rohit; Karp, Jeffrey M

    2011-01-01

    By leveraging the capacity to promote regeneration, stem cell therapies offer enormous hope for solving some of the most tragic illnesses, diseases, and tissue defects world-wide. However, a significant barrier to the effective implementation of cell therapies is the inability to target a large quantity of viable cells with high efficiency to tissues of interest. Systemic infusion is desired as it minimizes the invasiveness of cell therapy, and maximizes practical aspects of repeated doses. However, cell types such as mesenchymal stem cells exhibit a poor homing capability or lose their capacity to home following culture expansion (i.e. FASEB J 21:3197-3207, 2007; Circulation 108:863-868, 2003; Stroke: A Journal of Cerebral Circulation 32:1005-1011; Blood 104:3581-3587, 2004). To address this challenge, we have developed a simple platform technology to chemically attach cell adhesion molecules to the cell surface to improve the homing efficiency to specific tissues. This chemical approach involves a stepwise process including (1) treatment of cells with sulfonated biotinyl-N-hydroxy-succinimide to introduce biotin groups on the cell surface, (2) addition of streptavidin that binds to the biotin on the cell surface and presents unoccupied binding sites, and (3) attachment of biotinylated targeting ligands that promote adhesive interactions with vascular endothelium. Specifically, in our model system, a biotinylated cell rolling ligand, sialyl Lewisx (SLeX), found on the surface of leukocytes (i.e., the active site of the P-selectin glycoprotein ligand (PSGL-1)), is conjugated on MSC surface. The SLeX engineered MSCs exhibit a rolling response on a P-selectin coated substrate under shear stress conditions. This indicates that this approach can be used to potentially target P-selectin expressing endothelium in the more marrow or at sites of inflammation. Importantly, the surface modification has no adverse impact on MSCs' native phenotype including their multilineage differentiation capacity, viability, proliferation, and adhesion kinetics. We anticipate that the present approach to covalently modify the cell surface and immobilize required ligands is not limited to MSCs or the SLeX ligand. Therefore, this technology should have broad implications on cell therapies that utilize systemic administration and require targeting of cells to specific tissues. The approach may also be useful to promote specific cell-cell interactions. In this protocol, we describe the conjugation of SLeX on MSC surface and methods to study cell rolling behaviors of SLeX-modified MSCs on a P-selectin coated substrate using an in vitro flow chamber assay. We also provide a brief description of cell characterization assays that can be used to examine the impact of the chemical modification regimen. PMID:21431540

  7. EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Long-Term, Stable Differentiation of Human Embryonic Stem

    E-print Network

    Ryugo, David K.

    EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Long-Term, Stable Differentiation of Human Embryonic Stem Cell-Derived Neural Precursors Grafted into the Adult Mammalian Neostriatum IGOR NASONKIN Words. Cellular therapy · Embryonic stem cells · Neural differentiation · Neural induction · Neural stem

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

    Microsoft Academic Search

    Nóra Varga; Zoltán Veréb; Éva Rajnavölgyi; Katalin Német; Ferenc Uher; Balázs Sarkadi; Ágota Apáti

    2011-01-01

    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

  9. Combined effects of interleukin-7 and stem cell factor administration on lymphopoiesis after murine bone marrow transplantation.

    PubMed

    Chung, Brile; Min, Dullei; Joo, Lukas W; Krampf, Mark R; Huang, Jing; Yang, Yujun; Shashidhar, Sumana; Brown, Janice; Dudl, Eric P; Weinberg, Kenneth I

    2011-01-01

    The decreased ability of the thymus to generate T cells after bone marrow transplantation (BMT) is a clinically significant problem. Interleukin (IL)-7 and stem cell factor (SCF) induce proliferation, differentiation, and survival of thymocytes. Although previous studies have shown that administration of recombinant human IL-7 (rhIL-7) after murine and human BMT improves thymopoiesis and immune function, whether administration of SCF exerts similar effects is unclear. To evaluate independent or combinatorial effects of IL-7 and SCF in post-BMT thymopoiesis, bone marrow (BM)-derived mesenchymal stem cells transduced ex vivo with the rhIL-7 or murine SCF (mSCF) genes were cotransplanted with T cell-depleted BM cells into lethally irradiated mice. Although rhIL-7 and mSCF each improved immune reconstitution, the combination treatment had a significantly greater effect than either cytokine alone. Moreover, the combination treatment significantly increased donor-derived common lymphoid progenitors (CLPs) in BM, suggesting that transplanted CLPs expand more rapidly in response to IL-7 and SCF and may promote immune reconstitution. Our findings demonstrate that IL-7 and SCF might be therapeutically useful for enhancing de novo T cell development. Furthermore, combination therapy may allow the administration of lower doses of IL-7, thereby decreasing the likelihood of IL-7-mediated expansion of mature T cells. PMID:20713165

  10. Stem cells and diabetes

    Microsoft Academic Search

    G Berná; T León-Quinto; R Enseńat-Waser; E Montanya; F Martín; B Soria

    2001-01-01

    Diabetes mellitus is a metabolic disorder affecting 2–5% of the population. Transplantation of isolated islets of Langerhans from donor pancreata could be a cure for diabetes; however, such an approach is limited by the scarcity of the transplantation material and the long-term side effects of immunosuppressive therapy. These problems may be overcome by using a renewable source of cells, such

  11. Effects of Oxygen Concentration on the Proliferation and Differentiation of Mouse Neural Stem Cells In Vitro

    Microsoft Academic Search

    Nobutaka Horie; Kenji So; Takahiro Moriya; Naoki Kitagawa; Keisuke Tsutsumi; Izumi Nagata; Kazuyuki Shinohara

    2008-01-01

    Background and purpose Cerebral ischemia is known to elicit the activation of neural stem cells (NSCs); however its mechanism is not fully determined.\\u000a Although oxygen concentration is known to mediate many ischemic actions, there has been little attention given to the role\\u000a of pathological oxygen changes under cerebral ischemia on the activation of NSCs. We investigated the effects of various

  12. Neural crest stem cells from hair follicles and boundary cap have different effects on pancreatic islets in vitro.

    PubMed

    Kosykh, Anastasiia; Ngamjariyawat, Anongnad; Vasylovska, Svitlana; Konig, Niclas; Trolle, Carl; Lau, Joey; Mikaelyan, Arsen; Panchenko, Michael; Carlsson, Per-Ola; Vorotelyak, Ekaterina; Kozlova, Elena N

    2014-09-10

    Purpose: Neural crest stem cells derived from the boundary cap (bNCSCs), markedly promote survival, proliferation and function of insulin producing ?-cells in vitro and in vivo after coculture/transplantation with pancreatic islets [ 1, 2 ]. Recently, we have shown that beneficial effects on ?-cells require cadherin contacts between bNCSCs and ?-cells [ 3, 4 ]. Here we investigated whether hair follicle (HF) NCSCs, a potential source for human allogeneic transplantation, exert similar positive effects on ?-cells. Materials and Methods: We established cocultures of HF-NCSCs or bNCSCs from mice expressing enhanced green fluorescent protein together with pancreatic islets from DxRed expressing mice or NMRI mice and compared their migration towards islet cells and effect on proliferation of ?-cells as well as intracellular relations between NCSCs and islets using qRT-PCR analysis and immunohistochemistry. Results: Whereas both types of NCSCs migrated extensively in the presence of islets, only bNCSCs demonstrated directed migration toward islets, induced ?-cell proliferation and increased the presence of cadherin at the junctions between bNCSCs and ?-cells. Even in direct contact between ?-cells and HF-NCSCs, no cadherin expression was detected. Conclusions: These observations indicate that HF-NCSCs do not confer the same positive effect on ?-cells as demonstrated for bNCSCs. Furthermore, these data suggest that induction of cadherin expression by HF-NCSCs may be useful for their ability to support ?-cells in coculture and after transplantation. PMID:25077520

  13. Maintenance of mouse male germ line stem cells in vitro.

    PubMed

    Nagano, Makoto; Ryu, Buom-Yong; Brinster, Clayton J; Avarbock, Mary R; Brinster, Ralph L

    2003-06-01

    The proliferation and differentiation of a stem cell are regulated intrinsically by the stem cell and extrinsically by the stem cell niche. Elucidation of regulatory mechanisms of spermatogonial stem cells (SSCs), the stem cell of the postnatal male germ line, would be facilitated by in vitro studies that provide a defined microenvironment reconstituted ex vivo. We analyzed the effect of in vitro environment on the maintenance of adult and immature SSCs in a 7-day culture system. Although the number of adult and immature SSCs decreased in a time-dependent manner, nearly one in four stem cells (24%) could be maintained in vitro for 7 days. Stem cell maintenance was enhanced by coculture with OP9 bone marrow stroma or L fibroblast cell lines, addition of glial cell line-derived neurotrophic factor, or utilization of specific culture medium. In contrast, coculture with TM4 or SF7 Sertoli cell lines and addition of activin A or bone morphogenetic protein 4 (BMP4) reduced stem cell maintenance in vitro. Only 4% of the stem cells remained when cultured with TM4 cells or activin A, and 6% remained when cultured with SF7 cells or BMP4. These results lead to the hypothesis that suppression of germ cell differentiation improves in vitro maintenance of SSCs by interrupting the unidirectional cascade of spermatogenesis and blocking stem cell differentiation. PMID:12606373

  14. Cell Stem Cell Wnt Proteins Are Self-Renewal Factors

    E-print Network

    Bejerano, Gill

    Cell Stem Cell Article Wnt Proteins Are Self-Renewal Factors for Mammary Stem Cells and Promote.03.020 SUMMARY Adult stem cells have the ability to self-renew and to generate specialized cells. Self the organ develops postnatally, arises from stem cells, and is readily generated from transplanted cells. We

  15. MicroRNAs as novel regulators of stem cell fate

    PubMed Central

    Choi, Eunhyun; Choi, Eunmi; Hwang, Ki-Chul

    2013-01-01

    Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineage-specific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineage-specific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells. Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted. PMID:24179605

  16. Immunomodulation by Mesenchymal Stem Cells

    PubMed Central

    Abdi, Reza; Fiorina, Paolo; Adra, Chaker N.; Atkinson, Mark; Sayegh, Mohamed H.

    2008-01-01

    Mesenchymal stem cells (MSCs) are pluripotent stromal cells that have the potential to give rise to cells of diverse lineages. Interestingly, MSCs can be found in virtually all postnatal tissues. The main criteria currently used to characterize and identify these cells are the capacity for self-renewal and differentiation into tissues of mesodermal origin, combined with a lack in expression of certain hematopoietic molecules. Because of their developmental plasticity, the notion of MSC-based therapeutic intervention has become an emerging strategy for the replacement of injured tissues. MSCs have also been noted to possess the ability to impart profound immunomodulatory effects in vivo. Indeed, some of the initial observations regarding MSC protection from tissue injury once thought mediated by tissue regeneration may, in reality, result from immunomodulation. Whereas the exact mechanisms underlying the immunomodulatory functions of MSC remain largely unknown, these cells have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. This article focuses on recent advances that have broadened our understanding of the immunomodulatory properties of MSC and provides insight as to their potential for clinical use as a cell-based therapy for immune-mediated disorders and, in particular, type 1 diabetes. PMID:18586907

  17. Effects of Pulsed Electromagnetic Field on Differentiation of HUES-17 Human Embryonic Stem Cell Line

    PubMed Central

    Wu, Yi-Lin; Ma, Shi-Rong; Peng, Tao; Teng, Zeng-Hui; Liang, Xiang-Yan; Guo, Guo-Zhen; Zhang, Hai-Feng; Li, Kang-Chu

    2014-01-01

    Electromagnetic fields are considered to potentially affect embryonic development, but the mechanism is still unknown. In this study, human embryonic stem cell (hESC) line HUES-17 was applied to explore the mechanism of exposure on embryonic development to pulsed electromagnetic field (PEMF) for 400 pulses at different electric field intensities and the differentiation of HUES-17 cells was observed after PEMF exposure. The expression of alkaline phosphatase (AP), stage-specific embryonic antigen-3 (SSEA-3), SSEA-4 and the mRNA level and protein level of Oct4, Sox2 and Nanog in HUES-17 cells remained unchanged after PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m. Four hundred pulses PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m did not affect the differentiation of HUES-17 cells. The reason why electromagnetic fields affect embryonic development may be due to other mechanisms rather than affecting the differentiation of embryonic stem cells. PMID:25196518

  18. Stem-cell therapy for renal diseases

    Microsoft Academic Search

    Daniel J. Mollura; Joshua M. Hare; Hamid Rabb

    2003-01-01

    Significant attention is currently directed to the biological and therapeutic capabilities of stem cells for developing novel treatments for acute and chronic kidney diseases. To date, viable sources of stem cells for renal therapies include adult bone marrow and embryonic tissues, including the metanephric mesenchyme and mesonephros. Native adult kidney stem cells have yet to be identified. Systemically introduced stem

  19. Effects of the Endocrine-Disrupting Chemical DDT on Self-Renewal and Differentiation of Human Mesenchymal Stem Cells

    PubMed Central

    Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F.B.; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth P.

    2014-01-01

    Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear. Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology. Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs. Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPAR?), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells. Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs. Citation: Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK, McLachlan JA, Nephew KP, Burow ME, Bunnell BA. 2015. Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human mesenchymal stem cells. Environ Health Perspect 123:42–48;?http://dx.doi.org/10.1289/ehp.1408188 PMID:25014179

  20. Effect of auxin on Golgi-mediated cell wall synthesis in pea stem segments

    SciTech Connect

    Brummell, D.A.; Maclachlan, G.A.

    1986-04-01

    Stem segments of 7 day-old etiolated Pisum sativum seedlings were abraded using carborundum powder. Batches of segments were pulsed in (/sup 3/H) glucose followed by a chase in cold glucose in the presence or absence of 1AA, then homogenized by chopping with a razor blade. A rate-zonal centrifugation on a linear sucrose gradient was used to separate dictyosomes and secretory vesicles, and membrane-bound radioactivity determined as a measure of Golgi material in the cytoplasm. The amount of membrane-bound radioactivity was increased in tissues treated with 1AA for 30 min, indicative of an enhanced Golgi content in such segments. This increase thus precedes the sustained increase in auxin-stimulated growth of stem segments which occurs around 35-45 min after exposure to auxin and which is thought to be due to increased cell wall synthesis.

  1. EMBRYONIC STEM CELLS or INDUCED PLURIPOTENT STEM CELLS? A DNA INTEGRITY PERSPECTIVE

    E-print Network

    Boyer, Edmond

    stem cells and examine the three main sources of genomic abnormalities in iPSCs: (1) genomic variety1 EMBRYONIC STEM CELLS or INDUCED PLURIPOTENT STEM CELLS? A DNA INTEGRITY PERSPECTIVE Qiang Bai Gene Therapy 2013;13(2):93-8" #12;2 ABSTRACT Induced pluripotent stem cells (iPSCs) and embryonic stem

  2. Pluripotent Stem Cells: Sources and Characterization

    Microsoft Academic Search

    Sean P. Palecek

    \\u000a Pluripotent human stem cells, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, hold tremendous\\u000a promise as a source of progenitor cells and terminally differentiated cells in tissue engineering and regenerative medicine\\u000a applications. Pluripotent stem cells are capable of unlimited self-renewal and have the ability to differentiate to clinically\\u000a relevant cell types in each of the three germ

  3. Differential Effects of X-Rays and High-Energy {sup 56}Fe Ions on Human Mesenchymal Stem Cells

    SciTech Connect

    Kurpinski, Kyle [Department of Bioengineering, University of California-Berkeley, Berkeley, CA (United States); Jang, Deok-Jin; Bhattacharya, Sanchita; Rydberg, Bjorn [Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Chu, Julia; So, Joanna [Department of Bioengineering, University of California-Berkeley, Berkeley, CA (United States); Wyrobek, Andy [Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Li Song [Department of Bioengineering, University of California-Berkeley, Berkeley, CA (United States); Wang Daojing [Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States)], E-mail: djwang@lbl.gov

    2009-03-01

    Purpose: Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high-linear energy transfer (LET) {sup 56}Fe ions on human mesenchymal stem cells (hMSC). Methods and Materials: A multi-functional comparison was carried out to investigate the differential effects of X-rays and {sup 56}Fe ions on hMSC. The end points included modulation of key markers such as p53, cell cycle progression, osteogenic differentiation, and pathway and networks through transcriptomic profiling and bioinformatics analysis. Results: X-rays and {sup 56}Fe ions differentially inhibited the cell cycle progression of hMSC in a p53-dependent manner without impairing their in vitro osteogenic differentiation process. Pathway and network analyses revealed that cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy) X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched for high-dose (1 Gy) X-rays and {sup 56}Fe ions, with more significant effects from {sup 56}Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy {sup 56}Fe ions than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former while not for the latter. Conclusions: {sup 56}Fe ions exert more significant effects on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this study provides new mechanistic understandings of the relative health risks associated with low- and high-dose X-rays and high-LET space radiation.

  4. Generation of Lymphohematopoietic Cells from Embryonic Stem Cells in Culture

    Microsoft Academic Search

    Toru Nakano; Hiroaki Kodama; Tasuku Honjo

    1994-01-01

    An efficient system was developed that induced the differentiation of embryonic stem (ES) cells into blood cells of erythroid, myeloid, and B cell lineages by coculture with the stromal cell line OP9. This cell line does not express functional macrophage colony-stimulating factor (M-CSF). The presence of M-CSF had inhibitory effects on the differentiation of ES cells to blood cells other

  5. Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment

    PubMed Central

    Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

    2012-01-01

    Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e. the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to: (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. Here, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering. PMID:22101755

  6. Stem cell therapy for inflammatory bowel disease.

    PubMed

    Nagaishi, Kanna; Arimura, Yoshiaki; Fujimiya, Mineko

    2015-03-01

    Inflammatory bowel disease (IBD) could be curable by "immune rest" and correction of the genetic predisposition inherent in allogeneic hematopoietic stem cell transplantation. However, balancing risks against benefits remains challenging. The application of mesenchymal stem cells (MSCs) serving as a site-regulated "drugstore" is a recent concept, which suggests the possibility of an alternative treatment for many intractable diseases such as IBD. Depending on the required function of MSC, such as a cell provider, immune moderator, and/or trophic resource, MSC therapy should be optimized to maximize its therapeutic benefit. Therapeutic effects do not always require full engraftment of MSCs. Therefore, optimization of pleiotropic gut trophic factors produced by MSCs, which favoring not only regulating immune responses but also promoting tissue repair, must directly enhance new drug discoveries for treatment of IBD. Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and patients. However, the translational arm of stem cell science remains in a relatively primitive state. Although several clinical studies using MSCs have been initiated, early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, and can be resolved only by scientifically unveiling the mechanisms of therapeutic action. In the present review, the authors outline how such information would facilitate the critical steps in the paradigm shift from basic research on stem cell biology to clinical practice of regenerative medicine for conquering IBD in the near future. PMID:25618180

  7. Human Stem Cells for Craniomaxillofacial Reconstruction

    PubMed Central

    Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor

    2014-01-01

    Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction. PMID:24564584

  8. In vitro cytotoxicity effects of date palm (Phoenix dactylifera L.) pollen on neonate mouse spermatogonial stem cells.

    PubMed

    Mahaldashtian, Maryam; Makoolati, Zohreh; Ghorbanian, Mohamad Taghi; Naghdi, Majid; Kouhpayeh, Seyed Amin

    2015-03-01

    There is a fast growing tendency in the use of herbal remedies in developing countries. One of the traditional medicines used for male infertility treatment is date palm (Phoenix dactylifera) pollen (DPP). Isolated spermatogonial stem cells and sertoli cells using enzymatic digestion were grown in Dulbecco's modified Eagle's medium supplemented with 4% foetal bovine serum in the absence or presence of 0.06, 0.25 and 0.62 mg/mL concentrations of aqueous extract of DPP for 2 weeks. The assessment of mean number of the whole cells and the living cells showed that there were no significant differences between the mean viability percentage and proliferation rate between control and experimental groups (P>0.05). As there are no cytotoxicity effects of DPP in our cultural system, this system can be utilised for the enrichment or differentiation of these cells in clinical applications, cell replacement therapy, tissue regeneration and tissue engineering applications. PMID:25189835

  9. [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. PMID:15497791

  10. n induced pluripotent stem cell, or IPS cell, is a stem cell that has been created from an

    E-print Network

    A n induced pluripotent stem cell, or IPS cell, is a stem cell that has been created from an adult that reprogram the cell and transform it into a cell that has all the characteristics of an embryonic stem cell are the advantages of induced pluripotent stem cells? Bioethics: Induced stem cells have the obvious edge

  11. Hypoxia and Regulation of Cancer Cell Stemness

    PubMed Central

    Lin, Qun

    2014-01-01

    Spontaneous tumors often contain heterogeneous populations of tumor cells with different tumor-initiating potentials or cancer cellstemness.” Clonal heterogeneity can be traced to specific locations inside a tumor where clones with different metastatic capabilities are identified, suggesting that the tumor microenvironment can exert a significant effect on the evolution of different clonal populations. Hypoxia is a common feature of tumor microenvironments and has the potential to facilitate malignant progression. This chapter provides a synopsis of hypoxia-regulated pathways implicated in the maintenance of cancer stem cells. PMID:24272353

  12. Control of the Embryonic Stem Cell State

    E-print Network

    Young, Richard A.

    Embryonic stem cells and induced pluripotent stem cells hold great promise for regenerative medicine. These cells can be propagated in culture in an undifferentiated state but can be induced to differentiate into specialized ...

  13. MICROFLUIDIC CONTROL OF STEM CELL DIFFUSIBLE SIGNALING

    E-print Network

    Voldman, Joel

    MICROFLUIDIC CONTROL OF STEM CELL DIFFUSIBLE SIGNALING Katarina Blagovi, Lily Y. Kim, Alison M cell differentiation. KEYWORDS: Embryonic stem cells, microfluidic perfusion, diffusible signaling; they secrete molecules to which they respond. Microfluidics offers a potential solution to this challenge

  14. Learning about Cancer by Studying Stem Cells

    MedlinePLUS

    ... Science Home Page Learning About Cancer by Studying Stem Cells By Sharon Reynolds Posted January 8, 2014 Normally, ... of them are exploring the process by studying stem cells. Modeling Early Pancreatic Cancer Pancreatic cancer cells grown ...

  15. Cell Stem Cell Molecular Signatures of Human Induced Pluripotent

    E-print Network

    Sur, Mriganka

    cell lines. INTRODUCTION With the potential to differentiate into cells of three germ lineages ex vivoCell Stem Cell Article Molecular Signatures of Human Induced Pluripotent StemCells@molbio.mgh.harvard.edu DOI 10.1016/j.stem.2012.03.008 SUMMARY Although human induced pluripotent stem cells (hiPSCs) have

  16. Cell Stem Cell, Volume 12 Supplemental Information

    E-print Network

    Jacobsen, Steve

    Cell Stem Cell, Volume 12 Supplemental Information Stage-Specific Roles for Tet1 and Tet2 in DNA Demethylation in Primordial Germ Cells John J. Vincent, Yun Huang, Pao-Yang Chen, Suhua Feng, Joseph H). Arrowheads denote Oct4+ PGCs. #12;B: Flow cytometry of e10.5 Oct4gfp genital ridges (GR). GFP+ cells (green

  17. Alkaline Phosphatase in Stem Cells

    PubMed Central

    Štefková, Kate?ina; Procházková, Ji?ina; Pacherník, Ji?í

    2015-01-01

    Alkaline phosphatase is an enzyme commonly expressed in almost all living organisms. In humans and other mammals, determinations of the expression and activity of alkaline phosphatase have frequently been used for cell determination in developmental studies and/or within clinical trials. Alkaline phosphatase also seems to be one of the key markers in the identification of pluripotent embryonic stem as well as related cells. However, alkaline phosphatases exist in some isoenzymes and isoforms, which have tissue specific expressions and functions. Here, the role of alkaline phosphatase as a stem cell marker is discussed in detail. First, we briefly summarize contemporary knowledge of mammalian alkaline phosphatases in general. Second, we focus on the known facts of its role in and potential significance for the identification of stem cells.

  18. Patenting Human Genes and Stem Cells

    Microsoft Academic Search

    Enca Martin-Rendon; Derek J. Blake

    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

  19. Therapeutic implications of cancer stem cells

    Microsoft Academic Search

    Muhammad Al-Hajj; Michael W Becker; Max Wicha; Irving Weissman; Michael F Clarke

    2004-01-01

    Most cancers comprise a heterogenous population of cells with marked differences in their proliferative potential as well as the ability to reconstitute the tumor upon transplantation. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. In addition, dysregulation of stem cell self-renewal is a likely requirement for the development of cancer.

  20. The hematopoietic stem cell niche

    PubMed Central

    Park, Dongsu; Sykes, David B.; Scadden, David T.

    2014-01-01

    Hematopoietic stem cells (HSCs) possess the ability to self-renew and to differentiate to mature progeny along multiple different hematopoietic lineages. The function of HSCs depends upon the signals from surrounding cells found within the highly specialized microenvironment termed the hematopoietic stem cell niche. Understanding and exploiting the HSC niche is a goal of basic scientists and clinicians alike. Recent studies have focused on defining the cellular components and molecular factors critical to this microenvironment. Here we review recent findings, discuss unresolved questions, and examine the clinical implications of our current knowledge of the HSC niche. PMID:22201730

  1. Stem Cell Reports CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells

    E-print Network

    Wahl, Geoffrey M.

    Stem Cell Reports Report CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex cell behavior. Here, we identify CRIPTO and its cell- surface receptor GRP78 as regulators of stem cell differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast

  2. The Warburg effect version 2.0: metabolic reprogramming of cancer stem cells.

    PubMed

    Menendez, Javier A; Joven, Jorge; Cufí, Sílvia; Corominas-Faja, Bruna; Oliveras-Ferraros, Cristina; Cuyŕs, Elisabet; Martin-Castillo, Begońa; López-Bonet, Eugeni; Alarcón, Tomás; Vazquez-Martin, Alejandro

    2013-04-15

    When fighting cancer, knowledge on metabolism has always been important. Today, it matters more than ever. The restricted cataloging of cancer genomes is quite unlikely to achieve the task of curing cancer, unless it is integrated into metabolic networks that respond to and influence the constantly evolving cancer stem cell (CSC) cellular states. Once the genomic era of carcinogenesis had pushed the 1920s Otto Warburg's metabolic cancer hypothesis into obscurity for decades, the most recent studies begin to support a new developing paradigm, in which the molecular logic behind the conversion of non-CSCs into CSCs can be better understood in terms of the "metabolic facilitators" and "metabolic impediments" that operate as proximate openings and roadblocks, respectively, for the transcriptional events and signal transduction programs that ultimately orchestrate the intrinsic and/or microenvironmental paths to CSC cellular states. Here we propose that a profound understanding of how human carcinomas install a proper "Warburg effect version 2.0" allowing them to "run" the CSCs' "software" programs should guide a new era of metabolo-genomic-personalized cancer medicine. By viewing metabolic reprogramming of CSCs as an essential characteristic that allows dynamic, multidimensional and evolving cancer populations to compete successfully for their expansion on the organism, we now argue that CSCs bioenergetics might be another cancer hallmark. A definitive understanding of metabolic reprogramming in CSCs may complement or to some extent replace, the 30-y-old paradigm of targeting oncogenes to treat human carcinomas, because it can be possible to metabolically create non-permissive or "hostile" metabotypes to prevent the occurrence of CSC cellular states with tumor- and metastasis-initiating capacity. PMID:23549172

  3. The long-term psychosocial effects of haematopoetic stem cell transplantation.

    PubMed

    Gruber, U; Fegg, M; Buchmann, M; Kolb, H-J; Hiddemann, W

    2003-09-01

    The purpose of this study was to identify long-term psychosocial effects of allogenic, syngenic and autologous haematopoetic stem cell transplantation (HSCT) on relevant parameters (physical performance, role and sexual functioning, intimate relationships, professional and social rehabilitation). A total of 163 patients, who had undergone an autologous (11.6%), syngenic (3.1%) or allogenic (85.3%) HSCT at the Department of Internal Medicine III, Ludwig-Maximilians-University, during a preceding 16-year period, were asked to complete the Herschbach Questionnaire on Stress in Cancer Patients in order to evaluate their current psychosocial distress status. An additional questionnaire for demographic data was used. Reduced quality of life as a result of HSCT is restored to its pre-HSCT level by most patients within 2 years after transplantation (no differences between groups transplanted 2-5, 6-9 or >10 years ago). The majority of patients had serious problems with "fitness" (24%), followed by problems with "pain" (17.2%) and "fear/emotional stress" (14.1%). Professional reintegration is an important factor in patients' well-being. However, 30.7% of these patients did not return to work at all. Unemployed patients had significantly higher scores for pain, anxiety, sleep disorders, depression, impairments in social functioning, partnership and family life. Only 9.8% of all patients took part in a psychotherapeutic programme and 39.3% in a rehabilitation programme. Identifying strategies for risk patients (e.g. lower education and married) need to be developed in order to optimize support for this group. Although some patients show a higher distress score in anxiety/fear and psychophysical performance, only 9.8% of all patients took advantage of available psychotherapy. PMID:12919304

  4. Cryopreservation of Human Stem Cells for Clinical Application: A Review

    PubMed Central

    Hunt, Charles J.

    2011-01-01

    Summary Stem cells have been used in a clinical setting for many years. Haematopoietic stem cells have been used for the treatment of both haematological and non-haematological disease; while more recently mesenchymal stem cells derived from bone marrow have been the subject of both laboratory and early clinical studies. Whilst these cells show both multipotency and expansion potential, they nonetheless do not form stable cell lines in culture which is likely to limit the breadth of their application in the field of regenerative medicine. Human embryonic stem cells are pluripotent cells, capable of forming stable cell lines which retain the capacity to differentiate into cells from all three germ layers. This makes them of special significance in both regenerative medicine and toxicology. Induced pluripotent stem (iPS) cells may also provide a similar breadth of utility without some of the confounding ethical issues surrounding embryonic stem cells. An essential pre-requisite to the commercial and clinical application of stem cells are suitable cryopreservation protocols for long-term storage. Whilst effective methods for cryopreservation and storage have been developed for haematopoietic and mesenchymal stem cells, embryonic cells and iPS cells have proved more refractory. This paper reviews the current state of cryopreservation as it pertains to stem cells and in particular the embryonic and iPS cell. PMID:21566712

  5. Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

    SciTech Connect

    Kabiri, Azadeh, E-mail: z_kabiri@resident.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of)] [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esfandiari, Ebrahim, E-mail: esfandiari@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of)] [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Hashemibeni, Batool, E-mail: hashemibeni@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of)] [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Kazemi, Mohammad, E-mail: m_kazemi@med.mui.ac.i [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of)] [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Mardani, Mohammad, E-mail: mardani@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of)] [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esmaeili, Abolghasem, E-mail: abesmaeili@yahoo.com [Cell, Molecular and Developmental Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan (Iran, Islamic Republic of)] [Cell, Molecular and Developmental Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan (Iran, Islamic Republic of)

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We investigated effects of FGF-2 on hADSCs. Black-Right-Pointing-Pointer We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. Black-Right-Pointing-Pointer FGF-2 induces chondrogenesis in hADSCs, which Bullet Increasing information will decrease quality if hospital costs are very different. Black-Right-Pointing-Pointer The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

  6. 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. PMID:23257690

  7. Combined meta-analysis of systemic effects of allogeneic stem cell transplantation and systemic sclerosis

    PubMed Central

    2014-01-01

    Background Chronic graft-versus-host disease (cGVHD) is a major factor of morbidity and mortality for allogeneic stem cell transplantation (aSCT). The skin and internal organ involvement is the most common systemic complication of cGVHD and closely resembles systemic sclerosis (SSc). Circulating lymphocytes characterize the autoimmune nature of both conditions. Therefore we hypothesized that the common clinical manifestation (systemic organ and skin injury) and the common underlying players (lymphocytes) justify the combined meta-analysis of these diseases. Results The aSCT and SSc datasets were uploaded from Gene Expression Omnibus (GEO), a public functional genomics data repository. The available microarray studies of peripheral blood mononuclear cells (PBMCs) and isolated lymphocytes were limited to well established microarray platforms (Affymetrix, Agilent, Canvac, and Illumina) and experimental settings with ?10 patients per group. The resulting pools of data were merged by unique gene identifier and analyzed by the expression genome-wide association studies (eGWAS) coupled with the subtraction of the cGVHD+ and cGVHD? molecular signatures. The eGWAS was applied to 47 and 50 lymphocyte profiles from aSCT and SSc patients, respectively. The identified 35 candidates were represented by 8 known cGVHD genes (including CXCR4, LTBR and PML) and 28 new candidate genes (including SEPX1 and DNJGB1). The further mutual subtraction of cGVHD+ and cGVHD? candidates and pathway analysis identified a list of 25 genes. Seven of these genes belong to the fibroblast development and function pathway, consisting of the well known cGVHD genes CCND1, JUN, and FOS, and the new molecular targets MMP2, FOSB, TNFAIP8, and DUSP1. These genes become primary candidates for a potential link of systemic effects of cGVHD and SSc. Conclusions We designed a new approach for meta-analysis by combining data from different diseases using common clinical manifestation as a linker. This allowed us to power up the insufficient standalone meta-analysis of aSCT microarray studies, by adding SSc samples to the data pool. This new method has successfully identified novel molecular targets for systemic effects of both aSCT and SSc. We believe that this approach is generalizable and can be applied to an array of diseases with common clinical manifestations. PMID:24656173

  8. Stem cells: sources and therapies.

    PubMed

    Monti, Manuela; Perotti, Cesare; Del Fante, Claudia; Cervio, Marila; Redi, Carlo Alberto

    2012-01-01

    The historical, lexical and conceptual issues embedded in stem cell biology are reviewed from technical, ethical, philosophical, judicial, clinical, economic and biopolitical perspectives. The mechanisms assigning the simultaneous capacity to self-renew and to differentiate to stem cells (immortal template DNA and asymmetric division) are evaluated in the light of the niche hypothesis for the stemness state. The induction of cell pluripotency and the different stem cells sources are presented (embryonic, adult and cord blood). We highlight the embryonic and adult stem cell properties and possible therapies while we emphasize the particular scientific and social values of cord blood donation to set up cord blood banks. The current scientific and legal frameworks of cord blood banks are reviewed at an international level as well as allogenic, dedicated and autologous donations. The expectations and the challenges in relation to present-day targeted diseases like diabetes mellitus type I, Parkinson's disease and myocardial infarction are evaluated in the light of the cellular therapies for regenerative medicine. PMID:23283430

  9. MicroRNAs, stem cells and cancer stem cells

    PubMed Central

    Garg, Minal

    2012-01-01

    This review discusses the various regulatory characteristics of microRNAs that are capable of generating widespread changes in gene expression via post translational repression of many mRNA targets and control self-renewal, differentiation and division of cells. It controls the stem cell functions by controlling a wide range of pathological and physiological processes, including development, differentiation, cellular proliferation, programmed cell death, oncogenesis and metastasis. Through either mRNA cleavage or translational repression, miRNAs alter the expression of their cognate target genes; thereby modulating cellular pathways that affect the normal functions of stem cells, turning them into cancer stem cells, a likely cause of relapse in cancer patients. This present review further emphasizes the recent discoveries on the functional analysis of miRNAs in cancer metastasis and implications on miRNA based therapy using miRNA replacement or anti-miRNA technologies in specific cancer stem cells that are required to establish their efficacy in controlling tumorigenic potential and safe therapeutics. PMID:22993663

  10. Production of Uniparental Embryonic Stem Cell Lines

    Microsoft Academic Search

    Sigrid Eckardt; K. John McLaughlin

    \\u000a Embryonic stem cells, or induced pluripotent cells derived from somatic cells, can yield differentiated progeny with potential\\u000a applicability for tissue repair. This chapter describes the generation of embryonic stem cells from gamete-derived uniparental\\u000a embryos. These embryonic stem cells can be patient-derived and potentially histocompatible with the gamete donor. The production\\u000a of uniparental embryos followed by derivation of embryonic stem cells

  11. Cancer stem cells and cancer therapy

    Microsoft Academic Search

    Sara Soltanian; Maryam M. Matin

    2011-01-01

    Cancer stem cells (CSCs) are a subpopulation of tumour cells that possess the stem cell properties of self-renewal and differentiation.\\u000a Stem cells might be the target cells responsible for malignant transformation, and tumour formation may be a disorder of stem\\u000a cell self-renewal pathway. Epigenetic alterations and mutations of genes involved in signal transmissions may promote the\\u000a formation of CSCs. These

  12. --Taking STem Cell SCienCe from

    E-print Network

    Bieber, Michael

    -- Taking STem Cell SCienCe from Theory To TherapieS While The healing poTenTial of STem CellS one. produCed by our bodieS in an undifferenTiaTed STaTe, STem CellS evenTually SpeCialize Through na be tempered with a realistic as- sessment of where the development of stem cell therapies now stands. Most

  13. Effective surface-based cryopreservation of human embryonic stem cells by vitrification.

    PubMed

    Beier, A F J; Schulz, J C; Dörr, D; Katsen-Globa, A; Sachinidis, A; Hescheler, J; Zimmermann, H

    2011-12-01

    Human embryonic stem cells (hESCs) are candidates for many applications in the areas of regenerative medicine, tissue engineering, basic scientific research as well as pharmacology and toxicology. However, use of hESCs is limited by their sensitivity to freezing and thawing procedures. Hence, this emerging science needs new, reliable preservation methods for the long-term storage of large quantities of functional hESCs remaining pluripotent after post-thawing and culturing. Here, we present a highly efficient, surface based vitrification method for the cryopreservation of large numbers of adherent hESC colonies, using modified cell culture substrates. This technique results in much better post-thaw survival rate compared to cryopreservation in suspension and allows a quick and precise handling and storage of the cells, indicating low differentiation rates. PMID:21910982

  14. Valproic acid enhances anti-tumor effect of mesenchymal stem cell mediated HSV-TK gene therapy in intracranial glioma.

    PubMed

    Ryu, Chung Heon; Park, Kwang Ywel; Kim, Seong Muk; Jeong, Chang Hyun; Woo, Ji Sun; Hou, Yun; Jeun, Sin-Soo

    2012-05-11

    Suicide gene therapy of glioma based on herpes simplex virus type I thymidine kinase (HSV-TK) and prodrug ganciclovir (GCV) suffers from the lack of efficacy in clinical trials, which is mostly due to low transduction efficacy and absence of bystander effect in tumor cells. Recently, stem cells as cellular delivery vehicles of prodrug converting gene has emerged as a new treatment strategy for malignant glioma. In this study, we evaluated the anti-glioma effect of suicide gene therapy using human bone marrow mesenchymal stem cells expressing HSV-TK (MSCs-TK) combined with valproic acid (VPA), which can upregulate the gap junction proteins and may enhance the bystander effect of suicide gene therapy. Expression of HSV-TK in MSCs was confirmed by RT-PCR analysis and the sensitivity of MSCs-TK to GCV was assessed. A bystander effect was observed in co-cultures of MSCs-TK and U87 glioma cells by GCV in a dose-dependent manner. VPA induced the expression of the gap junction proteins connexin (Cx) 43 and 26 in glioma cell and thereby enhanced the bystander effect in co-culture experiment. The enhanced bystander effect was inhibited by the gap junction inhibitor 18-?-glycyrrhetinic acid (18-GA). Moreover, the combined treatment with VPA and MSCs-TK synergistically enhanced apoptosis in glioma cells by caspase activation. In vivo efficacy experiments showed that combination treatment of MSCs-TK and VPA significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with single-treatment groups. In addition, TUNEL staining also demonstrated a significant increase in the number of apoptotic cells in the combination treated group compared with single-treatment groups. Taken together, these results provide the rational for designing novel experimental protocols to increase bystander killing effect against intracranial gliomas using MSCs-TK and VPA. PMID:22525671

  15. Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells

    SciTech Connect

    Li, Yunfeng; Li, Jihua; Zhu, Songsong; Luo, En; Feng, Ge; Chen, Qianming [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China)] [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China); Hu, Jing, E-mail: drhu@vip.sohu.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China)] [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Strontium ranelate (SrR) inhibits proliferation of BMMSCs. Black-Right-Pointing-Pointer SrR increases osteoblastic but decreases adipocytic differentiation of BMMSCs. Black-Right-Pointing-Pointer SrR increases expression of Runx2, BSP and OCN by BMMSCs in osteogenic medium. Black-Right-Pointing-Pointer SrR decreases expression of PPAR{gamma}, aP2/ALBP and LPL by BMMSCs in adipogenic medium. -- Abstract: Strontium ranelate (SrR) was an effective anti-osteoporotic drug to increase bone formation and decrease bone resorption. However, reports about the effect of SR on osteoblastic and adipocytic differentiation from bone marrow mesenchymal stem cells (BMMSCs) are limited. The purpose of this study is to evaluate whether SrR affects the ability of BMMSCs to differentiate into osteoblasts or adipocytes. Rat BMMSCs were identified by flow cytometry and exposed to SR (0.1 and 1.0 mM Sr{sup 2+}) under osteogenic or adipogenic medium for 1 and 2 weeks. The proliferation and differentiation of BMMSCs were analyzed by MTT, alkaline phosphatase (ALP), Oil red O staining, quantitative real-time RT-PCR and Western blot assays. SrR significantly inhibited the proliferation, increased osteoblastic but decreased adipocytic differentiation of rat BMMSCs dose-dependently. In osteogenic medium, SrR increased the expression of ALP, the mRNA levels of Cbfa1/Runx2, bone sialoprotein, and osteocalcin by RT-PCR, and the protein levels of Cbfa1/Runx2 by Western blot. In adipogenic medium, SrR decreased the mRNA levels of PPAR{gamma}2, adipocyte lipid-binding protein 2 (aP2/ALBP), and lipoprotein lipase (LPL) by RT-PCR, and the protein expression of PPAR{gamma} in Western blot analysis. These results indicated that the effects of SrR to promote osteoblastic but inhibit adipocytic differentiation of BMMSCs might contribute to its effect on osteoporosis treatment.

  16. In Appreciation of Stem Cell Research Doners..............................................................1 Glossary ..........................................................................................................................4

    E-print Network

    Shapiro, Ehud

    #12;#12;In Appreciation of Stem Cell Research Doners ..........................................................................................................................4 Stem Cell Research at the Weizmann Institute of Science......................................................9 Germ-Line Stem Cell Differentiation

  17. 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

  18. Effects of different serum conditions on osteogenic differentiation of human adipose stem cells in vitro

    PubMed Central

    2013-01-01

    Introduction Currently, human adipose stem cells (hASCs) are differentiated towards osteogenic lineages using culture medium supplemented with L-ascorbic acid 2-phosphate (AsA2-P), dexamethasone (Dex) and beta-glycerophosphate (?-GP). Because this osteogenic medium (OM1) was initially generated for the differentiation of bone marrow-derived mesenchymal stem cells, the component concentrations may not be optimal for the differentiation of hASCs. After preliminary screening, two efficient osteogenic media (OM2 and OM3) were chosen to be compared with the commonly used osteogenic medium (OM1). To further develop the culture conditions towards clinical usage, the osteo-inductive efficiencies of OM1, OM2 and OM3 were compared using human serum (HS)-based medium and a defined, xeno-free medium (RegES), with fetal bovine serum (FBS)-based medium serving as a control. Methods To compare the osteo-inductive efficiency of OM1, OM2 and OM3 in FBS-, HS- and RegES-based medium, the osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, mineralization, and expression of osteogenic marker genes (runx2A, DLX5, collagen type I, osteocalcin, and ALP). Results In HS-based medium, the ALP activity increased significantly by OM3, and mineralization was enhanced by both OM2 and OM3, which have high AsA2-P and low Dex concentrations. ALP activity and mineralization of hASCs was the weakest in FBS-based medium, with no significant differences between the OM compositions due to donor variation. However, the qRT-PCR data demonstrated significant upregulation of runx2A mRNA under osteogenic differentiation in FBS- and HS-based medium, particularly by OM3 under FBS conditions. Further, the expression of DLX5 was greatly stimulated by OM1 to 3 on day 7 when compared to control. The regulation of collagen type I, ALP, and osteocalcin mRNA was modest under induction by OM1 to 3. The RegES medium was found to support the proliferation and osteogenic differentiation of hASCs, but the composition of the RegES medium hindered the comparison of OM1, OM2 and OM3. Conclusions Serum conditions affect hASC proliferation and differentiation significantly. The ALP activity and mineralization was the weakest in FBS-based medium, although osteogenic markers were upregulated on mRNA level. When comparing the OM composition, the commonly used OM1 was least effective. Accordingly, higher concentration of AsA2-P and lower concentration of Dex, as in OM2 and OM3, should be used for the osteogenic differentiation of hASCs in vitro. PMID:23415114

  19. Effects of Ionizing Radiation on Human Adipose Derived Mesenchymal Stem Cells and their Differentiation towards the Osteoblastic Lineage

    NASA Astrophysics Data System (ADS)

    Konda, Bikash; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther; Lau, Patrick

    Radiation exposure and musculoskeletal disuse are among the major challenges during space missions. Astronauts face the problem to lose bone calcium due to uncoupling of bone formation and resorption. Bone forming osteoblasts can be derived from the undifferentiated mesenchymal stem cell compartment (MSC). In this study, the ability of human adipose tissue derived stem cells (ATSC) to differentiate into the osteoblastic lineage was examined after radiation exposure in presence of medium supplementation with osteogenic additives (ß-glycerophosphate, ascorbic acid and dexamethasone). The SAOS-2 cell line (human osteosarcoma cell line) was used as control for osteoblastic differentiation. Changes in cellular morphology, cell cycle progression, as well as cellular radiation sensitivity were characterized after ionizing radiation exposure with X-rays and heavy ions (Ti). Rapidly proliferating SAOS-2 cells are less radiation-sensitive than slowly proliferating ATSC cells after X-ray (CFA: dose effect curves show D0 values of 1 Gy and 0.75 Gy for SAOS-2 and ATSC, respectively) exposure. Heavy ion (Ti) exposure resulted in a greater extent of cells accumulating in the G2/M phase of the cell cycle in a dose-dependent manner when compared to X-ray exposure. Differentiation of cells towards the osteoblastic lineage was quantified by hydroxyapatite (HA) deposition using Lonza OsteoImageTM mineralization assay. The deposition of HA after X- and Ti-irradiation for highly proliferating SAOS-2 cells showed a dose-dependent time delay while slowly proliferating ATSC showed no effect from radiation exposure. More detailed investigation is required to reveal the radiation dependent mechanism of bone loss in astronauts.

  20. Cancer Stem Cells, Endothelial Progenitors, and Mesenchymal Stem Cells: “Seed and Soil” Theory Revisited

    PubMed Central

    Lin, Edward H.; Jiang, Yixing; Deng, Yanhong; Lapsiwala, Ritu; Lin, Tongyu; Blau, C. Anthony

    2008-01-01

    Isolation of putative cancer stem cells (CSCs) in various tumors has generated much excitement among researchers who consider these cells the potential “culprits” behind resistance to conventional therapy. Both cancer and cardiovascular disease are believed to be stem cell disorders involving circulating endothelial progenitors (CEPs) and mesenchymal stem cells (MSCs). CD133 and CD44, markers of CSCs in many tumors, also enrich CEPs and MSCs, respectively. We propose an integrated tumorigenesis model that involves all three interdependent stem cell (CSC, CEP, MSC) compartments by revisiting the “seed and soil” model. Developing therapeutics that can effectively target CSCs and spare normal cardiovascular tissue will remain a challenge. Preliminary laboratory and clinical data on monitoring and targeting colon CSCs, using such a modeling system, are discussed. PMID:19259284

  1. Virgin birth: engineered heart muscle from parthenogenetic stem cells

    PubMed Central

    McSweeney, Sara J.; Schneider, Michael D.

    2013-01-01

    Cardiac muscle restitution, or true regeneration, is an unmet need in the treatment of myocardial infarction (MI), prompting a decade of study with stem cells of many kinds. Among key obstacles to effective cardiac cell grafting are the cost of autologous stem cell–derived cardiomyocytes, the ethical implications of using embryonic stem cell (ESC) products, immunological barriers to allogeneic cells, functional maturation beyond just the correct lineage decision, and the lack of durable engraftment. In this issue of the JCI, Didié and colleagues show that cardiomyocytes made from parthenogenetic stem cells (PSCs) and deployed as engineered heart muscle (EHM) may overcome all of these formidable barriers. PMID:23434596

  2. Role of stem cells in tooth bioengineering

    PubMed Central

    Singh, Kamleshwar; Mishra, Niraj; Kumar, Lakshya; Agarwal, Kaushal Kishore; Agarwal, Bhaskar

    2012-01-01

    The creation of teeth in the laboratory depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin, and enamel. This review focuses on the different sources of stem cells that have been used for making teeth in vitro. The search was performed from 1970 to 2012 and was limited to English language papers. The keywords searched on medline were ‘stem cells and dentistry,’ ‘stem cells and odontoblast,’ ‘stem cells and dentin,’ and ‘stem cells and ameloblasts.’

  3. Multipotent adult germline stem cells and embryonic stem cells functional proteomics revealed an important role of eukaryotic initiation factor 5A (Eif5a) in stem cell differentiation.

    PubMed

    Dihazi, Hassan; Dihazi, Gry H; Jahn, Olaf; Meyer, Sandra; Nolte, Jessica; Asif, Abdul R; Mueller, Gerhard A; Engel, Wolfgang

    2011-04-01

    Multipotent adult germline stem cells (maGSCs) are pluripotent cells that can be differentiated into somatic cells of the three primary germ layers. To highlight the protein profile changes associated with stem cell differentiation, retinoic acid (RA) treated mouse stem cells (maGSCs and ESCs) were compared to nontreated stem cells. 2-DE and DIGE reference maps were created, and differentially expressed proteins were further processed for identification. In both stem cell types, the RA induced differentiation resulted in an alteration of 36 proteins of which 18 were down-regulated and might be potential pluripotency associated proteins, whereas the other 18 proteins were up-regulated. These might be correlated to stem cell differentiation. Surprisingly, eukaryotic initiation factor 5A (Eif5a), a protein which is essential for cell proliferation and differentiation, was significantly down-regulated under RA treatment. A time-dependent investigation of Eif5a showed that the RA treatment of stem cells resulted in a significant up-regulation of the Eif5a in the first 48 h followed by a progressive down-regulation thereafter. This effect could be blocked by the hypusination inhibitor ciclopirox olamine (CPX). The alteration of Eif5a hypusination, as confirmed by mass spectrometry, exerts an antiproliferative effect on ESCs and maGSCs in vitro, but does not affect the cell pluripotency. Our data highlights the important role of Eif5a and its hypusination for stem cell differentiation and proliferation. PMID:21344951

  4. Immunobiology of mesenchymal stem cells

    PubMed Central

    Ma, S; Xie, N; Li, W; Yuan, B; Shi, Y; Wang, Y

    2014-01-01

    Mesenchymal stem cells (MSCs) can be isolated from almost all tissues and effectively expanded in vitro. Although their true in situ properties and biological functions remain to be elucidated, these in vitro expanded cells have been shown to possess potential to differentiate into specific cell lineages. It is speculated that MSCs in situ have important roles in tissue cellular homeostasis by replacing dead or dysfunctional cells. Recent studies have demonstrated that in vitro expanded MSCs of various origins have great capacity to modulate immune responses and change the progression of different inflammatory diseases. As tissue injuries are often accompanied by inflammation, inflammatory factors may provide cues to mobilize MSCs to tissue sites with damage. Before carrying out tissue repair functions, MSCs first prepare the microenvironment by modulating inflammatory processes and releasing various growth factors in response to the inflammation status. In this review, we focus on the crosstalk between MSCs and immune responses and their potential clinical applications, especially in inflammatory diseases. PMID:24185619

  5. Effects of intravenous human umbilical cord blood CD34+ stem cell therapy versus levodopa in experimentally induced Parkinsonism in mice

    PubMed Central

    Abo-Grisha, Noha; Abo-Elmatty, Dina M.; Abdel-Hady, Zenab

    2013-01-01

    Introduction Parkinsonism is a neurodegenerative disease with impaired motor function. The current research was directed to investigate the effect of CD34+ stem cells versus levodopa in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism. Material and methods Mice were divided into 4 groups; saline-injected, MPTP: received four MPTP injections (20 mg/kg, i.p.) at 2 h intervals, MPTP groups treated with levodopa/carbidopa (100/10 mg/kg/twice/day for 28 days) or single intravenous injection of 106 CD34+ stem cells/mouse at day 7 and allowed to survive until the end of week 5. Results Levodopa and stem cells improved MPTP-induced motor deficits; they abolished the difference in stride length, decreased percentage of foot slip errors and increased ambulation, activity factor and mobility duration in parkinsonian mice (p < 0.05). Further, they significantly (p < 0.05) increased striatal dopamine (85.3 ±4.3 and 110.6 ±5.3) and ATP levels (10.6 ±1.1 and 15.5 ±1.14) compared to MPTP (60.1 ±3.9 pmol/g and 3.6 ±0.09 mmol/g, respectively) (p < 0.05). Moreover, mitochondrial DNA from mice treated with levodopa or stem cells was in intact form; average concentration was (52.8 ±3.01 and 107.8 ±8.6) and no appreciable fragmentation of nuclear DNA was found compared to MPTP group. Regarding tyrosine hydroxylase (TH) immunostaining, stem cell group showed a marked increase of percentage of TH-immunopositive neurons (63.55 ±5.2) compared to both MPTP (37.6 ±3.1) and levodopa groups (41.6 ±3.5). Conclusions CD34+ cells ameliorated motor, biochemical and histological deficits in MPTP-parkinsonian mice, these effects were superior to those produced by levodopa that would be promising for the treatment of PD. PMID:24482663

  6. Effects of Interleukin-17A on Osteogenic Differentiation of Isolated Human Mesenchymal Stem Cells

    PubMed Central

    Osta, Bilal; Lavocat, Fabien; Eljaafari, Assia; Miossec, Pierre

    2014-01-01

    Objectives: Rheumatoid arthritis (RA) is characterized by defective bone repair and excessive destruction and ankylosing spondylitis (AS) by increased ectopic bone formation with syndesmophytes. Since TNF-? and IL-17A are involved in both diseases, this study investigated their effects on the osteogenic differentiation of isolated human bone marrow-derived mesenchymal stem cells (hMSCs). Methods: Differentiation of hMSCs into osteoblasts was induced in the presence or absence of IL-17A and/or TNF-?. Matrix mineralization (MM) was evaluated by alizarin red staining and alkaline phosphatase (ALP) activity. mRNA expression was measured by qRT-PCR for bone morphogenetic protein (BMP)-2 and Runx2, genes associated with osteogenesis, DKK-1, a negative regulator of osteogenesis, Schnurri-3 and receptor activator of nuclear factor kappa B ligand (RANKL), associated with the cross talk with osteoclasts, and TNF-? receptor type I and TNF-? receptor type II (TNFRII). Results: TNF-? alone increased both MM and ALP activity. IL-17A alone increased ALP but not MM. Their combination was more potent. TNF-? alone increased BMP2 mRNA expression at 6 and 12?h. These levels decreased in combination with IL-17A at 6?h only. DKK-1 mRNA expression was inhibited by TNF-? and IL-17A either alone or combined. Supporting an imbalance toward osteoblastogenesis, RANKL expression was inhibited by TNF-? and IL-17A. However, TNF-? but not IL-17 alone decreased Runx2 mRNA expression at 6?h. In parallel, TNF-? but not IL-17 alone increased Schnurri-3 expression with a synergistic effect with their combination. This may be related to an increase of TNFRII overexpression. Conclusion: IL-17 increased the effects of TNF-? on bone matrix formation by hMSCs. However, IL-17 decreased the TNF-?-induced BMP2 inhibition. Synergistic interactions between TNF-? and IL-17 were seen for RANKL inhibition and Schnurri-3 induction. Such increase of Schnurri-3 may in turn activate osteoclasts leading to bone destruction as in RA. Conversely, in the absence of osteoclasts, this could promote ectopic bone formation as in AS. PMID:25228904

  7. Chemical approaches to studying stem cell biology.

    PubMed

    Li, Wenlin; Jiang, Kai; Wei, Wanguo; Shi, Yan; Ding, Sheng

    2013-01-01

    Stem cells, including both pluripotent stem cells and multipotent somatic stem cells, hold great potential for interrogating the mechanisms of tissue development, homeostasis and pathology, and for treating numerous devastating diseases. Establishment of in vitro platforms to faithfully maintain and precisely manipulate stem cell fates is essential to understand the basic mechanisms of stem cell biology, and to translate stem cells into regenerative medicine. Chemical approaches have recently provided a number of small molecules that can be used to control cell self-renewal, lineage differentiation, reprogramming and regeneration. These chemical modulators have been proven to be versatile tools for probing stem cell biology and manipulating cell fates toward desired outcomes. Ultimately, this strategy is promising to be a new frontier for drug development aimed at endogenous stem cell modulation. PMID:23266890

  8. Cell Stem Cell An Expanded Oct4 Interaction Network: Implications

    E-print Network

    Babu, M. Madan

    Cell Stem Cell Resource An Expanded Oct4 Interaction Network: Implications for Stem Cell Biology is key in embryonic stem cell identity and reprogramming. Insight into its part- ners should illuminate set of Oct4-binding proteins in mouse embryonic stem cells. We find that Oct4 asso- ciates

  9. The Effect of Human Platelet-Rich Plasma on Adipose-Derived Stem Cell Proliferation and Osteogenic Differentiation

    PubMed Central

    Tavakolinejad, Sima; Khosravi, Mohsen; Mashkani, Baratali; Ebrahimzadeh Bideskan, Alireza; Sanjar Mossavi, Nasser; Parizadeh, Seyyed Mohammad Reza; Hamidi Alamdari, Daryoush

    2014-01-01

    Background: The cultured mesenchymal stem cells (MSC) have been used in many clinical trials; however, there are still some concerns about the cultural conditions. One concern is related to the use of FBS as a widely used xenogeneic supplement in the culture system. Human platelet-rich plasma (hPRP) is a candidate replacement for FBS. In this study, the effect of hPRP on MSC proliferation and osteogenic differentiation has been evaluated. Methods: Human adipose-derived stem cells (hADSC) were expanded. Cells from the third passage were characterized by flow cytometric analysis and used for in vitro experiments. Resazurin and alizarin red stains were used for cell proliferation and osteogenic differentiation assays, respectively. Results: Treatment with hPRP resulted in a statistically significant increase in cell proliferation compare to the negative control group (P<0.001). Cell proliferation in the 15% hPRP group was also significantly higher than that in the 10% hPRP group (P<0.05). Additionally, it caused less osteogenic differentiation of the hADSC compared to the FBS (P<0.001), but in comparison to negative control, it caused acceptable mineralization (P<0.001). Conclusion: These findings indicate that hPRP not only improves the proliferation but also it can be a suitable substitution in osteogenic differentiation for clinical purposes. However, the clinical application value of hPRP still needs more investigation. PMID:24842141

  10. Inner ear stem cells derived feeder layer promote directional differentiation of amniotic fluid stem cells into functional neurons.

    PubMed

    Zong, Ling; Chen, Kaitian; Zhou, Wei; Jiang, Di; Sun, Liang; Zhang, Xuemei; Jiang, Hongyan

    2014-10-01

    Intact spiral ganglion neurons are required for cochlear implantation or conventional hearing amplification as an intervention for sensorineural hearing loss. Treatment strategies to replace the loss of spiral ganglion neurons are needed. Recent reports have suggested that amniotic fluid-derived stem cells are capable of differentiating into neuron-like cells in response to cytokines and are not tumorigenic. Amniotic fluid stem cells represent a potential resource for cellular therapy of neural deafness due to spiral ganglion pathology. However, the directional differentiation of amniotic fluid stem cells is undetermined in the absence of cytokines and the consequence of inner ear supporting cells from the mouse cochlea organ of Corti on the differentiation of amniotic fluid stem cells remains to be defined. In an effort to circumvent these limitations, we investigated the effect of inner ear stem cells derived feeder layer on amniotic fluid stem cells differentiation in vitro. An inner ear stem cells derived feeder layer direct contact system was established to induce differentiation of amniotic fluid stem cells. Our results showed that inner ear stem cells derived feeder layer successfully promoted directional differentiation of amniotic fluid stem cells into neurons with characteristics of functionality. Furthermore, we showed that Wnt signaling may play an essential role in triggering neurogenesis. These findings indicate the potential use of inner ear stem cells derived feeder layer as a nerve-regenerative scaffold. A reliable and effective amniotic fluid stem cell differentiation support structure provided by inner ear stem cells derived feeder layer should contribute to efforts to translate cell-based strategies to the clinic. PMID:25124154

  11. The Effects of GDF-5 and Uniaxial Strain on Mesenchymal Stem Cells in 3-D Culture

    PubMed Central

    Urdaneta, Alfonso R.; Barba, David; Esmende, Sean; McAllister, David R.

    2008-01-01

    Recent endeavors in tissue engineering have attempted to identify the optimal parameters to create an artificial ligament. Both mechanical and biochemical stimulation have been used by others to independently modulate growth and differentiation, although few studies have explored their interactions. We applied previously described fabrication techniques to create a highly porous (90%–95% porosity, 212–300 ?m), 3-D, bioabsorbable polymer scaffold (polycaprolactone). Scaffolds were coated with bovine collagen, and growth and differentiation factor 5 (GDF-5) was added to half of the scaffolds. Scaffolds were seeded with mesenchymal stem cells and cultured in a custom bioreactor under static or cyclic strain (10% strain, 0.33 Hz) conditions. After 48 hours, both mechanical stimulation and GDF-5 increased mRNA production of collagen I, II, and scleraxis compared to control; tenascin C production was not increased. Combining stimuli did not change gene expression; however, cellular metabolism was 1.7 times higher in scaffolds treated with both stimuli. We successfully grew a line of mesenchymal stem cells in 3-D culture, and our initial data indicate mechanical stimulation and GDF-5 influenced cellular activity and mRNA production; we did not, however, observe additive synergism with the mechanical and biological stimuli. PMID:18535869

  12. Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes

    Microsoft Academic Search

    L. Vija; D. Farge; J.-F. Gautier; P. Vexiau; C. Dumitrache; A. Bourgarit; F. Verrecchia; J. Larghero

    2009-01-01

    Mesenchymal stem cells (MSCs) are multipotent non-haematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential together with their effects on immune response make them a promising therapeutic tool for severe refractory autoimmune diseases. Type 1 diabetes is characterized by T cell-mediated

  13. Adult Stem Cells: Sources and Characterization

    Microsoft Academic Search

    Hitoshi Okochi

    \\u000a Basic and clinical research on adult stem cells is progressing rapidly. New technology that can generate iPS (induced pluripotent\\u000a stem cells) cells from various types of tissue may completely change the stem cell world and regenerative medicine. In terms\\u000a of clinical applications, both bone marrow and skin are very attractive sources of adult stem cells because they are highly\\u000a accessible

  14. Tracking of Stem Cells In Vivo

    Microsoft Academic Search

    Yingli Fu; Dara L. Kraitchman

    \\u000a Clinical and basic studies of stem-cell-based therapies have shown promising results for cardiovascular diseases. Despite\\u000a a rapid transition from animal studies to clinical trials, the mechanisms of action by which stem cells improve heart function\\u000a remain largely unknown. To optimize stem cell therapies in patients, a method to noninvasively monitor stem cell delivery\\u000a and to evaluate cell survival, biodistribution, and

  15. Stem Cells in the Infarcted Heart

    Microsoft Academic Search

    Dinender K. Singla

    2010-01-01

    Stem cell transplantation is currently generating a significant interest for use in the future treatment of cardiovascular\\u000a diseases. Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical\\u000a trials as bone marrow stem cells did not show significant improvement in cardiac function following transplantation. Experimental\\u000a stem cell studies raised

  16. Progress and Prospects for Stem Cell Engineering

    E-print Network

    Schaffer, David V.

    to a pluripotent state by ectopic introduction of reprogramming factors Embryonic stem (ES) cells: cells isolated tissue. In 1981, mouse embryonic stem cells (mESCs) were successfully cultured and demonstratedProgress and Prospects for Stem Cell Engineering Randolph S. Ashton,1 Albert J. Keung,1 Joseph

  17. Mini Review Neuronal stem cells in adults

    Microsoft Academic Search

    Hans-Christian Bauer; Herbert Tempfer; Gustav Bernroider; Hannelore Bauer

    Summary Neuronal stem cells are like other tissue-specific stem cells, undifferentiated cells which can proliferate and may give rise to glia and neurons. They are present in mammalians throughout the entire life and are supposed to play an important role in renewal of neurons. However, little is known about the origin, phenotypic expression and function of neuronal stem cells in

  18. The therapeutic potential of neural stem cells

    Microsoft Academic Search

    Gianvito Martino; Stefano Pluchino

    2006-01-01

    Recent evidence shows that transplantation of neural stem\\/precursor cells may protect the central nervous system from inflammatory damage through a 'bystander' mechanism that is alternative to cell replacement. This novel mechanism, which might improve the success of transplantation procedures, is exerted by undifferentiated neural stem cells, the functional characteristics of which are regulated by important stem cell regulators released by

  19. HEMATOPOIESIS AND STEM CELLS Brief report

    E-print Network

    Zandstra, Peter W.

    be instrumental in advancing HSC-based therapies. Using an expansion system previously shown to increase hematopoi stem cells,10 endothelial progenitor cells,11 and brain and colon cancer stem cells.12,13 The absenceHEMATOPOIESIS AND STEM CELLS Brief report TheAC133 CD38 , but not the rhodamine-low, phenotype

  20. Extinction models for cancer stem cell therapy

    Microsoft Academic Search

    Mary Sehl; Hua Zhou; Janet S. Sinsheimer; Kenneth L. Lange

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of

  1. Effects of reconstituted collagen matrix on fates of mouse embryonic stem cells before and after induction for chondrogenic differentiation.

    PubMed

    Yeung, Chiu W; Cheah, Kathryn; Chan, Danny; Chan, Barbara P

    2009-10-01

    Embryonic stem (ES) cells are pluripotent cells with great potential in regenerative medicine. However, controlling their differentiation toward homogeneous lineages is challenging. In this study, we aim to investigate the effects of reconstituted 3D collagen matrix on the fates of mouse ES (mES) cells before and after induction for chondrogenic differentiation. Specifically, mES cells were encapsulated and cultured in 3D collagen microspheres and exposed to induction signals at different time points. Growth characteristics and differentiation status of mES cells were then evaluated. Collagen microspheres provided a suitable microenvironment supporting mES cell growth and maintaining their undifferentiated status for certain period of time. At later time points, the proportion of undifferentiated mES cells gradually decreased, accompanied by increasing proportions of mesenchymal progenitor cells. This suggests the inductive role of collagen matrix in differentiating mES cells toward mesenchymal lineages. Moreover, a lower initial collagen monomer concentration facilitated the differentiation of mES cells into chondrogenic lineages, while induction at a later time point associated with a more advanced stage of chondrogenic differentiation. This indicates that both the initial collagen concentration and the time to induce differentiation significantly affected the fates of mES cells. This study contributes to future development of ES cell-based therapies. PMID:19331579

  2. Adult Stem Cell Therapy for Autoimmune Disease

    PubMed Central

    Choi, Eun Wha

    2009-01-01

    Many studies of autologous hematopoietic stem cell transplantation (HSCT) and allogeneic HSCT have been conducted for autoimmune disease in various animal models. Because of the substantial risk of morbidity and mortality associated with allogeneic bone marrow transplantation, autologous transplants justified trying this approach in patient with severe autoimmune disease who were refractory to current treatments. Remission was achieved in some of the patients and some of them relapsed. Recently, many in vitro studies have reported that mesenchymal stem cells (MSC) have immunomodulatory properties and immunosuppressive effects on MHC-mismatched lymphocytes proliferation by inhibiting naďve, memory and activated T cells, B cell, NK cells and dendritic cells. In addition, adipose tissue-derived MSC (AT-MSC) are becoming an alternative source of MSC for therapeutic applications because adipose tissues are abundant, easily accessible, easily obtainable with little patient discomfort and large amounts of AT-MSC can be easily obtained. A large body of in vitro research has shown that AT-MSC have same or similar immunomodulatory effects with bone marrow derived MSC. Drawing on this finding, the increasing numbers of researchers have turned on their attention to preclinical studies on AT-MSC. As this new path of research evolves with subsequent reports, MSC would make a significant contribution to stem cell therapy or combination therapy for ameliorating symptoms and curing autoimmune disease. By searching and studying the appropriate therapeutic gene, the therapeutic gene transfected stem cell therapy will be able to acquire the synergy effect and the combined advantage of gene therapy and stem cell therapy. PMID:24855531

  3. Lung Epithelial Stem Cells

    Microsoft Academic Search

    Magnus Karl Magnusson; Olafur Baldursson; Thorarinn Gudjonsson

    \\u000a The lung epithelium is structurally and functionally a complex tissue composed of different cell types. It is exposed to toxic\\u000a agents and pathogens that can with time result in various lung diseases, including lung cancer. The major cell types in the\\u000a proximal tracheobronchial part are basal cells, goblet cells, ciliated cells, and cells of the submucosal glands. Further\\u000a down the

  4. III. Stem Cells and Their Asymmetric Cell Divisions Stem cells to synapses: regulation of self-renewal and differentiation in

    E-print Network

    Kazama, Hokto

    III. Stem Cells and Their Asymmetric Cell Divisions Stem cells to synapses: regulation of self fates is a key step in the therapeutic use of stem cells to repair tissues after damage or disease. We are investigating the genetic networks that regulate neural stem cells in Drosophila. Stem cells can divide

  5. Hematopoietic stem cells: an overview.

    PubMed

    Mosaad, Youssef Mohamed

    2014-12-01

    Considerable efforts have been made in recent years in understanding the mechanisms that govern hematopoietic stem cell (HSC) origin, development, differentiation, self-renewal, aging, trafficking, plasticity and transdifferentiation. Hematopoiesis occurs in sequential waves in distinct anatomical locations during development and these shifts in location are accompanied by changes in the functional status of the stem cells and reflect the changing needs of the developing organism. HSCs make a choice of either self-renewal or committing to differentiation. The balance between self-renewal and differentiation is considered to be critical to the maintenance of stem cell numbers. It is still under debate if HSC can rejuvenate infinitely or if they do not possess ''true" self-renewal and undergo replicative senescence such as any other somatic cell. Gene therapy applications that target HSCs offer a great potential for the treatment of hematologic and immunologic diseases. However, the clinical success has been limited by many factors. This review is intended to summarize the recent advances made in the human HSC field, and will review the hematopoietic stem cell from definition through development to clinical applications. PMID:25457002

  6. Human Mesenchymal Stem Cells Signals Regulate Neural Stem Cell Fate

    Microsoft Academic Search

    Lianhua Bai; Arnold Caplan; Donald Lennon; Robert H. Miller

    2007-01-01

    Neural stem cells (NSCs) differentiate into neurons, astrocytes and oligodendrocytes depending on their location within the\\u000a central nervous system (CNS). The cellular and molecular cues mediating end-stage cell fate choices are not completely understood.\\u000a The retention of multipotent NSCs in the adult CNS raises the possibility that selective recruitment of their progeny to specific\\u000a lineages may facilitate repair in a

  7. Stem Cell and Research in Plastic Surgery

    PubMed Central

    2014-01-01

    Regenerative medicine using stem cells has progressed significantly over the last decade. Plastic surgeons historically have used tissues of human being to restore various defect sites and utilized a single cell lines for the tissue regeneration. The cell sources (autologous or allogeneic), cell types (embryonic stem cell or adult stem cell), and source of tissues (bone marrow, muscle, adipose, cartilage, or blood) are very important for stem cell-based tissue coverage. Embryonic stem cells are pluripotent precursors obtained from the inner cell mass of the blastocyst and reported to be used for preventing muscle atrophy after peripheral nerve injury. Multipotent adult stem cells are easily accessed for plastic surgeons during many routine procedures. This article briefly review the current state of overall stem cell research and clinical applications in the plastic surgical field. PMID:25473205

  8. Cancer Stem Cells Found in Pancreatic Tumors

    Cancer.gov

    Researchers have detected cancer stem cells in tumors from patients with pancreatic cancer. Experiments in mice suggest that these cancer stem cells may help explain the aggressive growth and spread of pancreatic tumors seen in patients.

  9. Becoming a Blood Stem Cell Donor

    MedlinePLUS

    ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 319 Subscription preferences ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  10. Retinal Stem Cells

    Microsoft Academic Search

    Ani V. Das; Jackson James; Sreekumaran Edakkot; Iqbal Ahmad

    The vertebrate retina is a well-characterized central nervous system (CNS) structure, consisting of seven major cell types,\\u000a which in adult are arranged in a stereotypical laminar organization. These cell types are born in an evolutionarily conserved\\u000a temporal sequence: the majority of retinal ganglion cells (RGCs), horizontal cells, amacrine cells, and cone photoreceptors\\u000a are born during early histogenesis, whereas the majority

  11. Adult Stem Cell Transplantation: Is Gender a Factor in Stemness?

    PubMed Central

    Tajiri, Naoki; Duncan, Kelsey; Borlongan, Mia C.; Pabon, Mibel; Acosta, Sandra; de la Pena, Ike; Hernadez-Ontiveros, Diana; Lozano, Diego; Aguirre, Daniela; Reyes, Stephanny; Sanberg, Paul R.; Eve, David J.; Borlongan, Cesar V.; Kaneko, Yuji

    2014-01-01

    Cell therapy now constitutes an important area of regenerative medicine. The aging of the population has mandated the discovery and development of new and innovative therapeutic modalities to combat devastating disorders such as stroke. Menstrual blood and Sertoli cells represent two sources of viable transplantable cells that are gender-specific, both of which appear to have potential as donor cells for transplantation in stroke. During the subacute phase of stroke, the use of autologous cells offers effective and practical clinical application and is suggestive of the many benefits of using the aforementioned gender-specific cells. For example, in addition to being exceptionally immunosuppressive, testis-derived Sertoli cells secrete many growth and trophic factors and have been shown to aid in the functional recovery of animals transplanted with fetal dopaminergic cells. Correspondingly, menstrual blood cells are easily obtainable and exhibit angiogenic characteristics, proliferative capability, and pluripotency. Of further interest is the ability of menstrual blood cells, following transplantation in stroke models, to migrate to the infarct site, secrete neurotrophic factors, regulate the inflammatory response, and be steered towards neural differentiation. From cell isolation to transplantation, we emphasize in this review paper the practicality and relevance of the experimental and clinical use of gender-specific stem cells, such as Sertoli cells and menstrual blood cells, in the treatment of stroke. PMID:25170809

  12. Epithelial Stem Cells: A Folliculocentric View

    Microsoft Academic Search

    George Cotsarelis

    2006-01-01

    Putative epithelial stem cells were identified in the hair follicle bulge as quiescent “label retaining cells”. The study of these cells was hindered until the identification of bulge cell molecular markers, such as CD34 expression and K15 promoter activity. This allowed for the isolation and characterization of bulge cells from mouse follicles. Bulge cells possess stem cell characteristics, including multipotency,

  13. Stem cell therapy for intervertebral disk regeneration.

    PubMed

    Gou, Shanmiao; Oxentenko, Shawn C; Eldrige, Jason S; Xiao, Lizu; Pingree, Mathew J; Wang, Zhen; Perez-Terzic, Carmen; Qu, Wenchun

    2014-11-01

    Intervertebral disk degeneration has been considered an irreversible process characterized by a decrease in cell viability, attenuation of proteoglycan and type II collagen synthesis, and dehydration of nucleus pulposus. Stem cell therapy specifically addresses the degenerative process and offers a potentially effective treatment modality. Current preclinical studies show that mesenchymal stem cells have the capacity to repair degenerative disks by differentiation toward chondrocyte-like cells, which produce proteoglycans and type II collagen. There has been evidence that mesenchymal stem cell transplantation into the intervertebral disk increases the intradiskal magnetic resonance imaging T2 signal intensity, increases the disk height, and decreases the degenerative grade in animal models. Appropriate selection of cell carriers/matrix is important because it may prevent cell leakage into the spinal canal and provide an environment that facilitates cell proliferation and differentiation. Although human cell therapy trials for degenerative disk disease are on the horizon, potential issues might arise. The authors hereby review the current state of regenerative cell therapy in degenerative disk disease, with emphasis in cell source, techniques for cellular expansion, induction, transplantation, potential benefit, and risks of the use of this novel medical armamentarium in the treatment of degenerative disk disease. PMID:25122106

  14. Regenerative Potential of Endometrial Stem Cells: A Mini Review

    PubMed Central

    Ghobadi, Farnaz; Mehrabani, Davood; Mehrabani, Golnoush

    2015-01-01

    Recent findings in stem cell biology have opened a new window in regenerative medicine. The endometrium possesses mesenchymal stem cells (MSCs) called endometrial stem cells (EnSCs) having specific regenerative properties linked to adult stem cells. They contribute in tissue remodeling and engineering and were shown to have immuno-modulating effects. Many clinical trials were undertaken to ascertain the therapeutic potential of EnSCS. In this mini review, we showed that EnSCs are readily available sources of adult stem cells in the uterus that can be highlighted for their renewable multipotent and differentiation properties. This cell population may be a practical solution of choice in reproductive biology, regenerative medicine and autologous stem cell therapy. PMID:25606470

  15. Intra-arterial transplantation of low-dose stem cells provides functional recovery without adverse effects after stroke.

    PubMed

    Fukuda, Yuhtaka; Horie, Nobutaka; Satoh, Katsuya; Yamaguchi, Susumu; Morofuji, Youichi; Hiu, Takeshi; Izumo, Tsuyoshi; Hayashi, Kentaro; Nishida, Noriyuki; Nagata, Izumi

    2015-04-01

    Cell transplantation therapy for cerebral infarction has emerged as a promising treatment to reduce brain damage and enhance functional recovery. We previously reported that intra-arterial delivery of bone marrow mesenchymal stem cells (MSCs) enables superselective cell administration to the infarct area and results in significant functional recovery after ischemic stroke in a rat model. However, to reduce the risk of embolism caused by the transplanted cells, an optimal cell number should be determined. At 24 h after middle cerebral artery occlusion and reperfusion, we administered human MSCs (low dose: 1 × 10(4) cells; high dose: 1 × 10(6) cells) and then assessed functional recovery, inflammatory responses, cell distribution, and mortality. Rats treated with high- or low-dose MSCs showed behavioral recovery. At day 8 post-stroke, microglial activation was suppressed significantly, and interleukin (IL)-1? and IL-12p70 were reduced in both groups. Although high-dose MSCs were more widely distributed in the cortex and striatum of rats, the degree of intravascular cell aggregation and mortality was significantly higher in the high-dose group. In conclusion, selective intra-arterial transplantation of low-dose MSCs has anti-inflammatory effects and reduces the adverse effects of embolic complication, resulting in sufficient functional recovery of the affected brain. PMID:25398358

  16. Effects of pH and thermally sensitive hybrid gels on osteogenic differentiation of mesenchymal stem cells.

    PubMed

    Dai, Zhuojun; Shu, Yinglan; Wan, Chao; Wu, Chi

    2015-04-01

    Osteoblastic differentiation of mesenchymal stem cells from bone marrow is an essential step for bone formation. The osteogenesis is normally induced by chemical mediators. Recent laboratory studies have revealed that mechanical properties of an extracellular matrix, typically hydrogels with different modules, also affect the fate of stem cells. The question is how to adjust their mechanical properties inside the body in biomedical applications. In this study, we designed/used a novel extracellular matrix, namely, a hybrid gel made of billions of injectable small thermally and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) microgels whose swelling at the body pH and temperature physically jammed them and mesenchymal stem cells together, which enabled us to in situ apply an adjustable mechanical stress on those embedded stem cells. By treating the cell layer with the microgels, we found that an earlier incorporation of the microgels significantly increases the alkaline phosphatase activity, while a later addition of the microgels after the primary calcium deposition enhances the extracellular matrix mineralization in the mesenchymal stem cells cultures accompanied by up-regulation of osteogenic marker genes expression, presumably due to the calcium fixation by the carboxyl groups inside the microgels and the physical contact between the microgels and mesenchymal stem cells layers. These microgels provide an extracellular matrix microenvironment to affect the fate and biological behavior of mesenchymal stem cells, facilitating their potential applications in regenerative therapies. PMID:25361919

  17. Effects of Exercise in Combination With Epoetin Alfa During High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

    PubMed Central

    Coleman, Elizabeth A.; Coon, Sharon K.; Kennedy, Robert L.; Lockhart, Kimberly D.; Stewart, Carol B.; Anaissie, Elias J.; Barlogie, Bart

    2008-01-01

    Purpose/Objectives To determine the effect of aerobic and strength resistance training and epoetin alfa (EPO) therapy on transfusions, stem cell collections, transplantation recovery, and multiple myeloma tre