Sample records for stem cells effect

  1. Paracrine effects of haematopoietic cells on human mesenchymal stem cells

    PubMed Central

    Zhou, Shuanhu

    2015-01-01

    Stem cell function decline during ageing can involve both cell intrinsic and extrinsic mechanisms. Bone and blood formation are intertwined in bone marrow, therefore haematopoietic cells and bone cells could be extrinsic factors for each other. In this study, we assessed the paracrine effects of extrinsic factors from haematopoietic cells on human mesenchymal stem cells (MSCs). Our data showed that haematopoietic cells stimulate proliferation, osteoblast differentiation and inhibit senescence of MSCs; TNF-?, PDGF-?, Wnt1, 4, 6, 7a and 10a, sFRP-3 and sFRP-5 are dominantly expressed in haematopoietic cells; the age-related increase of TNF-? in haematopoietic cells may perform as a negative factor in the interactions of haematopoietic cells on MSCs via TNF-? receptors and then activating NF-?B signaling or Wnt/?-catenin signaling to induce senescence and reduce osteoblast differentiation in MSCs. In conclusion, our data demonstrated that there are paracrine interactions of haematopoietic cells on human MSCs; immunosenescence may be one of the extrinsic mechanisms by which skeletal stem cell function decline during human skeletal ageing. PMID:26030407

  2. Schwann cell mediated trophic effects by differentiated mesenchymal stem cells

    Microsoft Academic Search

    Daljeet Mahay; Giorgio Terenghi; Susan G. Shawcross

    2008-01-01

    Mesenchymal stem cells were isolated from the bone marrow of rats and differentiated to provide a functional substitute for slow growing Schwann cells for peripheral nerve regeneration. To assess the properties of the differentiated mesenchymal stem cell, the cells were co-cultured with dorsal root ganglia and the secretion of the neurotrophic factors and the neurite outgrowth was evaluated. The neurite

  3. Adverse effect of high glucose concentration on stem cell therapy.

    PubMed

    Saki, Najmaldin; Jalalifar, Mohammad Ali; Soleimani, Masoud; Hajizamani, Saeideh; Rahim, Fakher

    2013-01-01

    Stem cell therapy could have great potential for the treatment of a wide variety of diseases. Stem cells might have the ability to differentiate into a widespread cell types, and to repopulate and revitalize the damaged cells with healthy tissue, and improve its performance. We provide here the evidence supporting the critical use of stem cell as a treatment in disease conditions existing with high glucose complaint such as diabetes. The reduction of glucose stimulated cell proliferation and high glucose enhanced apoptosis in rat model, which may be a problem in therapeutic strategies based on ex vivo expansion of stem cell, and may also propagate the development of osteoporosis in high glucose complaint such as diabetes. This leads to the hypothesis that, high glucose could be more deleterious to stem cell therapy that may be due to the aggravation of oxidative stress triggered by high glucose. These findings may help to understand the possible reasons associated with high glucose induced detrimental effects on stem cells as well as provide novel therapeutic strategies for preventing the adverse effects of glucose on the development and progression of stem cells in patients with diabetes. PMID:24505533

  4. Stem Cells

    Microsoft Academic Search

    Gwen Lomberk

    2007-01-01

    In this issue, ‘Pancreatology and the Web’ focuses on stem cell research, one of the 21st century’s most exciting areas of science. Stem cell research has been advancing our knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Although still in its infancy, this field also offers a revolutionary

  5. The Multiparametric Effects of Hydrodynamic Environments on Stem Cell Culture

    PubMed Central

    Kinney, Melissa A.; Sargent, Carolyn Y.

    2011-01-01

    Stem cells possess the unique capacity to differentiate into many clinically relevant somatic cell types, making them a promising cell source for tissue engineering applications and regenerative medicine therapies. However, in order for the therapeutic promise of stem cells to be fully realized, scalable approaches to efficiently direct differentiation must be developed. Traditionally, suspension culture systems are employed for the scale-up manufacturing of biologics via bioprocessing systems that heavily rely upon various types of bioreactors. However, in contrast to conventional bench-scale static cultures, large-scale suspension cultures impart complex hydrodynamic forces on cells and aggregates due to fluid mixing conditions. Stem cells are exquisitely sensitive to environmental perturbations, thus motivating the need for a more systematic understanding of the effects of hydrodynamic environments on stem cell expansion and differentiation. This article discusses the interdependent relationships between stem cell aggregation, metabolism, and phenotype in the context of hydrodynamic culture environments. Ultimately, an improved understanding of the multifactorial response of stem cells to mixed culture conditions will enable the design of bioreactors and bioprocessing systems for scalable directed differentiation approaches. PMID:21491967

  6. 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

  7. Cell Stem Cell Stem Cell States, Fates,

    E-print Network

    Peterson, Carsten

    and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, Lund SE-223 62, Sweden 4Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, LundCell Stem Cell Review Stem Cell States, Fates, and the Rules of Attraction Tariq Enver,1 Martin

  8. Effective culture conditions for the induction of pluripotent stem cells

    Microsoft Academic Search

    Minoru Okada; Masahiro Oka; Yoshihiro Yoneda

    2010-01-01

    BackgroundInduced pluripotent stem (iPS) cells, which are functionally comparable to embryonic stem (ES) cells, can be generated from mouse fibroblasts by expression of a defined set of transcription factors Oct4, Sox2, Klf4, and c-Myc. Since iPS cells are generated from somatic cells, they provide an invaluable source of pluripotent stem cells for cell transplantation therapy that does not present ethical

  9. Decellularized ECM effects on human mesenchymal stem cell stemness and differentiation.

    PubMed

    Rao Pattabhi, Sudhakara; Martinez, Jessica S; Keller, Thomas C S

    2014-01-01

    Microenvironment extracellular matrices (ECMs) influence cell adhesion, proliferation and differentiation. The ECMs of different microenvironments have distinctive compositions and architectures. This investigation addresses effects ECMs deposited by a variety of cell types and decellularized with a cold-EDTA protocol have on multipotent human mesenchymal stromal/stem cell (hMSC) behavior and differentiation. The cold-EDTA protocol removes intact cells from ECM, with minimal ECM damage and contamination. The decellularized ECMs deposited by cultured hMSCs, osteogenic hMSCs, and two smooth muscle cell (SMC) lines were tested for distinctive effects on the behavior and differentiation of early passage ('naďve') hMSC plated and cultured on the decellularized ECMs. Uninduced hMSC decellularized ECM enhanced naďve hMSC proliferation and cell motility while maintaining stemness. Decellularized ECM deposited by osteogenic hMSCs early in the differentiation process stimulated naďve hMSCs osteogenesis and substrate biomineralization in the absence of added dexamethasone, but this osteogenic induction potential was lower in ECMs decellularized later in the osteogenic hMSC differentiation process. Decellularized ECMs deposited by two smooth muscle cell lines induced naďve hMSCs to become smooth muscle cell-like with distinctive phenotypic characteristics of contractile and synthetic smooth muscle cells. This investigation demonstrates a useful approach for obtaining functional cell-deposited ECM and highlights the importance of ECM specificity in influencing stem cell behavior. PMID:25578478

  10. Immunomodulatory effects of umbilical cord-derived mesenchymal stem cells.

    PubMed

    Shawki, Shereen; Gaafar, Taghrid; Erfan, Hadeel; El Khateeb, Engy; El Sheikhah, Ahmad; El Hawary, Rabab

    2015-06-01

    Umbilical cord blood (UCB) is of great interest as a source of stem cells for use in cellular therapies. The immunomodulatory effect of mesenchymal stem cells (MSCs) originating from bone marrow, adipose tissue and amniotic membrane has previously been reported. In this study, MSCs were isolated from UCB with the aim of evaluating their immunomodulatory effects on proliferation of PB lymphocytes by two different techniques; namely, 5-bromo-2-deoxyuridine ELISA and a carboxy fluorescein diacetate succinimidyl ester flow cytometric technique. MSCs were isolated from UCB, propagated until Passage four, and then characterized for cell surface markers by flow cytometry and ability to differentiate towards osteocytes and adipocytes. Immunosuppressive effects on PB lymphocytes were examined by co-culturing mitomycin C-treated UCB MSCs with mitogen-stimulated lymphocytes for 72?hr. Thereafter, proliferation of lymphocytes was detected by CFSE flow cytometry and colorimetric ELISA. The titers of cytokines in cell culture supernatant were also assayed to clarify possible mechanisms of immunomodulation. UCB MSCs suppressed mitogen-stimulated lymphocyte proliferation, which occurs via both cell-cell contact and cytokine secretion. Titers of transforming growth factor beta and IL 10 increased, whereas that of IFN-? decreased in the supernatants of co-cultures. Thus, UCB MSCs suppress the proliferation of mitogen-stimulated lymphocytes. However further in vivo studies are required to fully evaluate the immunomodulatory effects of UCB MSCs. PMID:25869421

  11. The Effects of Graphene Nanostructures on Mesenchymal Stem Cells

    PubMed Central

    Lalwani, Gaurav; Kanakia, Shruti; Sitharaman, Balaji

    2014-01-01

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

  12. 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

  13. Effects of cell-cell contact and oxygen tension on chondrogenic differentiation of stem cells.

    PubMed

    Cao, Bin; Li, Zhenhua; Peng, Rong; Ding, Jiandong

    2015-09-01

    While cell condensation has been thought to enhance chondrogenesis, no direct evidence so far confirms that cell-cell contact itself increases chondrogenic differentiation of stem cells, since the change of cell-cell contact is usually coupled with those of other cell geometry cues and soluble factors in cell culture. The present study semi-quantitatively examined the effect of cell-cell contact in a decoupled way. We fabricated two-dimensional micropatterns with cell-adhesive peptide arginine-glycine-aspartate (RGD) microdomains on a nonfouling poly(ethylene glycol) (PEG) hydrogel. Mesenchymal stem cells (MSCs) were well localized on the microdomains for a long time. Based on our micropattern design, single MSCs or cell clusters with given cell numbers (1, 2, 3, 6 and 15) and a similar spreading area per cell were achieved on the same substrate, thus the interference of soluble factor difference from cell autocrine and that of cell spreading area were ruled out. After 9-day chondrogenic induction, collagen II was stained to characterize the chondrogenic induction results; the mRNA expression levels of SOX9, collagen II, aggrecan, HIF-1? and collagen I were also detected. The statistics confirmed unambiguously that the extent of the chondrogenic differentiation increased with cell-cell contact, and even a linear relation between differentiation extent and contact extent was established within the examined range. The cell-cell contact effect worked under both hypoxia (5% O2) and normoxia (21% O2) conditions, and the hypoxia condition promoted the chondrogenic induction of MSCs on adhesive microdomains more efficiently than the normoxia condition under the same cell-cell contact extents. PMID:26113183

  14. 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

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

    Microsoft Academic Search

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

    2011-01-01

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

  16. Stem Cell Aging: Potential Effects on Health and Mortality

    Microsoft Academic Search

    Erin Oakley; Alison Miller; Amanda Waterstrat; Carol Swiderski; Ying Liang; Gary Van Zant

    Aging in a statistical sense is the increasing probability of death with increasing time of an organism’s existence (1, 2).\\u000a Can we extrapolate this to self-regenerating tissues and most particularly to the stem cells that drive the replenishment\\u000a of lost and damaged cells throughout life? To be succinct, how close is the linkage between the vitality of the stem cell

  17. Mesenchymal autologous stem cells.

    PubMed

    Falavigna, Asdrubal; da Costa, Jaderson Costa

    2015-02-01

    The use of cell-based therapies for spinal cord injuries has recently gained prominence as a potential therapy or component of a combination strategy. Experimental and clinical studies have been performed using mesenchymal stem cell therapy to treat spinal cord injuries with encouraging results. However, there have been reports on the adverse effects of these stem cell-based therapies, especially in the context of tumor modulation. This article surveys the literature relevant to the potential of mesenchymal autologous stem cells for spinal cord injuries and their clinical implications. PMID:23402865

  18. 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.

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

    PubMed

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

    2005-06-01

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

  20. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

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

  1. 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.

  2. Stem cell niches

    Microsoft Academic Search

    V. V. Terskikh; A. V. Vasiliev; E. A. Vorotelyak

    2007-01-01

    The nature of the stem cell niche and its interaction with stem cells is one of fundamental problems in the biology of stem\\u000a cells. Stem cell niches are formed during ontogeny. A niche can remain vacant and exist independently of stem cells; however,\\u000a stem cell self-renewal cannot be maintained for long periods outside of the niche except for particular conditions,

  3. Epithelial Cells Stem Cells

    E-print Network

    Schüler, 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

  4. Epidermal Stem Cells

    Microsoft Academic Search

    V. V. Terskikh; A. V. Vasil'ev

    2001-01-01

    Epidermis contains a compartment of stem cells but currently there is no common criterion to recognize individual stem cells with any confidence. Epidermis appears to contain stem cells of different levels of maturity and it is very likely that the main repository of epidermal stem cells is located in the hair follicle from which cells can emigrate into epidermis and

  5. Stem Cell Information: Glossary

    MedlinePLUS

    ... medicine Reproductive cloning Signals Somatic cell Somatic cell nuclear transfer (SCNT) Somatic (adult) stem cell Stem cells ... refer to an animal produced by somatic cell nuclear transfer (SCNT) or parthenogenesis . Cloning —See Clone . Cord ...

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

    PubMed

    Jilkine, Alexandra; Gutenkunst, Ryan N

    2014-03-01

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

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

    PubMed Central

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

    2013-01-01

    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

  8. 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

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

    Microsoft Academic Search

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

    2009-01-01

    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

  10. Cell Stem Cell Perspective

    E-print Network

    Zhang, Yi

    for genetic alterations that facilitate cell prop- agation (Figure 1C). In addition to these causes, certainCell Stem Cell Perspective Genetic and Epigenetic Variations in iPSCs: Potential Causes Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA 4Department of Genetics, Harvard

  11. 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

  12. Toward ‘SMART’ stem cells

    Microsoft Academic Search

    T Cheng

    2008-01-01

    Stem cell research is at the heart of regenerative medicine, which holds great promise for the treatment of many devastating disorders. However, in addition to hurdles posed by well-publicized ethical issues, this emerging field presents many biological challenges. What is a stem cell? How are embryonic stem cells different from adult stem cells? What are the physiological bases for therapeutically

  13. The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes

    Microsoft Academic Search

    Soraya Tabera; José A. Pérez-Simón; María Díez-Campelo; Luis I. Sánchez-Abarca; Belén Blanco; Antonio López; Ana Benito; Enrique Ocio; Fermín M. Sánchez-Guijo; Consuelo Cańizo; Jesús F. San Miguel

    2008-01-01

    Background Mesenchymal stem cells are multilineage non-hematopoietic progenitor cells that play a key role in supporting the lymphohematopoietic system. Their distribution in bone marrow and sec- ondary lymphoid organs allows an intimate interaction with T- and B-lymphocytes. While their effect on T-lymphocytes has been extensively analyzed, data on the effect of mesenchymal stem cells on B cells are more limited.

  14. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

    PubMed Central

    Li, Ying-bo; Wang, Yan; Tang, Ji-ping; Chen, Di; Wang, Sha-li

    2015-01-01

    Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10–80 ?M ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 ?M ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy. PMID:26109949

  15. Different Effects of BORIS/CTCFL on Stemness Gene Expression, Sphere Formation and Cell Survival in Epithelial Cancer Stem Cells

    PubMed Central

    Alberti, Loredana; Losi, Lorena; Leyvraz, Serge; Benhattar, Jean

    2015-01-01

    Cancer stem cells are cancer cells characterized by stem cell properties and represent a small population of tumor cells that drives tumor development, progression, metastasis and drug resistance. To date, the molecular mechanisms that generate and regulate cancer stem cells are not well defined. BORIS (Brother of Regulator of Imprinted Sites) or CTCFL (CTCF-like) is a DNA-binding protein that is expressed in normal tissues only in germ cells and is re-activated in tumors. Recent evidences have highlighted the correlation of BORIS/CTCFL expression with poor overall survival of different cancer patients. We have previously shown an association of BORIS-expressing cells with stemness gene expression in embryonic cancer cells. Here, we studied the role of BORIS in epithelial tumor cells. Using BORIS-molecular beacon that was already validated, we were able to show the presence of BORIS mRNA in cancer stem cell-enriched populations (side population and spheres) of cervical, colon and breast tumor cells. BORIS silencing studies showed a decrease of sphere formation capacity in breast and colon tumor cells. Importantly, BORIS-silencing led to down-regulation of hTERT, stem cell (NANOG, OCT4, SOX2 and BMI1) and cancer stem cell markers (ABCG2, CD44 and ALDH1) genes. Conversely, BORIS-induction led to up-regulation of the same genes. These phenotypes were observed in cervical, colon and invasive breast tumor cells. However, a completely different behavior was observed in the non-invasive breast tumor cells (MCF7). Indeed, these cells acquired an epithelial mesenchymal transition phenotype after BORIS silencing. Our results demonstrate that BORIS is associated with cancer stem cell-enriched populations of several epithelial tumor cells and the different phenotypes depend on the origin of tumor cells. PMID:26185996

  16. 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

  17. 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

  18. 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 *Correspondence: peter.zandstra@utoronto.ca DOI 10.1016/j.stem.2012.01.003 SUMMARY Clinical hematopoietic implementations of hematopoietic stem cells (HSCs) and their deriva- tives further increase interest in strategies

  19. 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

  20. Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells

    Microsoft Academic Search

    Ying Liang; Gary Van Zant; Stephen J. Szilvassy

    2005-01-01

    To test the hypothesis that aging has negative effects on stem-cell homing and engraftment, young or old C57BL\\/6 bone marrow (BM) cells were injected, using a limiting-dilution, competitive transplanta- tion method, into old or young Ly5 con- genic mice. Numbers of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) recovered from BM or spleen were measured and compared with the

  1. 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

  2. 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.

  3. Effect of Bacterial Infection on Stem Cell Pattern in Porifera

    Microsoft Academic Search

    Werner E. G. Müller; Márcio Reis Custódio; Matthias Wiens; Carla Zilberberg; Amélie Châtel; Isabel M. Müller; Heinz C. Schröder

    \\u000a Multicellular organisms derived from one common ancestor, the Urmetazoa. The only living fossils, which can testify about\\u000a the earliest evolutionary processes in Metazoa on the molecular level are sponges (phylum: Porifera). The present study outlines\\u000a that stem cells may play essential roles in cellular specialization, embryogenesis and sponge Bauplan formation, using the\\u000a demosponge Suberites domuncula as a model. Data indicate

  4. Effect of Reishi polysaccharides on human stem\\/progenitor cells

    Microsoft Academic Search

    Wan-Yu Chen; Wen-Bin Yang; Chi-Huey Wong; Daniel Tzu-Bi Shih

    2010-01-01

    The polysaccharide fraction of Ganoderma lucidum (F3) was found to benefit our health in many ways by influencing the activity of tissue stem\\/progenitor cells. In this study, F3 was found to promote the adipose tissue MSCs’ aggregation and chondrosphere formation, with the increase of CAM (N-CAM, I-CAM) expressions and autokine (BMP-2, IL-11, and aggrecan) secretions, in an in vitro chondrogenesis

  5. Effect of Varying Fluid Shear Stress on Cancer Stem Cell Viability & Protein Expression

    NASA Astrophysics Data System (ADS)

    Domier, Ria; Kim, Yonghyun; Dozier, David; Triantafillu, Ursula

    2013-11-01

    Cancer stem cells cultured in vitro in stirred bioreactors are exposed to shear stress. By observing the effect of shear stress on cancer stem cell viability, laboratory cell growth could be optimized. In addition, metastasized cancer stem cells in vivo are naturally exposed to shear stress, a factor influencing stem cell differentiation, while circulating in the bloodstream. Changes in protein expression after exposure to shear stress could allow for identification and targeting of circulating cancer cells. In this study, blood flow through capillaries was simulated by using a syringe pump to inject suspensions of Kasumi-1 leukemia stem cells into model blood vessels composed of PEEK tubing 125 microns in diameter. The Hagen-Poisseuille equation was used to solve for operating flow rates based on specified amounts of shear stress. After exposure, cell counts and viabilities were observed using an optical microscope and proteins were analyzed using Western blotting. It was observed that at a one minute exposure to stress, cell viability increased as the amount of shear was increased from 10 to 60 dynes per square centimeter. Results from this research are applicable to optimization of large-scale stem cell growth in bioreactors as well as to the design of targeted cancer therapies. Cancer stem cells cultured in vitro in stirred bioreactors are exposed to shear stress. By observing the effect of shear stress on cancer stem cell viability, laboratory cell growth could be optimized. In addition, metastasized cancer stem cells in vivo are naturally exposed to shear stress, a factor influencing stem cell differentiation, while circulating in the bloodstream. Changes in protein expression after exposure to shear stress could allow for identification and targeting of circulating cancer cells. In this study, blood flow through capillaries was simulated by using a syringe pump to inject suspensions of Kasumi-1 leukemia stem cells into model blood vessels composed of PEEK tubing 125 microns in diameter. The Hagen-Poisseuille equation was used to solve for operating flow rates based on specified amounts of shear stress. After exposure, cell counts and viabilities were observed using an optical microscope and proteins were analyzed using Western blotting. It was observed that at a one minute exposure to stress, cell viability increased as the amount of shear was increased from 10 to 60 dynes per square centimeter. Results from this research are applicable to optimization of large-scale stem cell growth in bioreactors as well as to the design of targeted cancer therapies. Funding from NSF REU grant #1062611 is gratefully acknowledged.

  6. 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

  7. Potent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy.

    PubMed

    Zhang, Yuelin; Liang, Xiaoting; Liao, Songyan; Wang, Weixin; Wang, Junwen; Li, Xiang; Ding, Yue; Liang, Yingmin; Gao, Fei; Yang, Mo; Fu, Qingling; Xu, Aimin; Chai, Yuet-Hung; He, Jia; Tse, Hung-Fat; Lian, Qizhou

    2015-01-01

    Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel "cell-free" therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects. PMID:26057572

  8. Potent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy

    PubMed Central

    Zhang, Yuelin; Liang, Xiaoting; Liao, Songyan; Wang, Weixin; Wang, Junwen; Li, Xiang; Ding, Yue; Liang, Yingmin; Gao, Fei; Yang, Mo; Fu, Qingling; Xu, Aimin; Chai, Yuet-Hung; He, Jia; Tse, Hung-Fat; Lian, Qizhou

    2015-01-01

    Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel “cell-free” therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects. PMID:26057572

  9. Selective effect of INGAP-PP upon mouse embryonic stem cell differentiation toward islet cells.

    PubMed

    Francini, Flavio; Del Zotto, Héctor; Massa, María L; Gagliardino, Juan J

    2009-02-25

    We evaluated the effect of islet neogenesis-associated protein pentadecapeptide (INGAP-PP) upon islet beta- and non-beta cell differentiation from mouse embryonic stem (mES) cells. ES-D3 cell lines were cultured following Lumelsky's protocol with or without INGAP-PP (5 microg/ml) at different stages. Gene expression was quantified using qPCR. mES cells were fixed and immunostained using anti insulin-, somatostatin-, glucagon-, Pdx-1-, Ngn-3-, Nkx-6.1 and PGP9.5 specific antibodies. PCNA was used to measure replication rate. Bcl(2) (immunostaining) and caspase-3 (enzyme activity and gene expression) were determined as apoptosis markers. INGAP-PP increased IAPP, Glut-2, Kir-6.2, SUR-1 and insulin gene expression, and the percentage of insulin-immunostained cells. Conversely, INGAP-PP reduced significantly glucagon and somatostatin gene expression and immunopositivity. While nestin gene expression was not affected, there was a significant reduction in the percentage of PGP9.5-immunostained cells. Pdx-1 gene expression increased by 115% in INGAP-PP treated cells, as well as the percentage of Pdx-1, Ngn-3 and Nkx-6.1 immunopositive cells. Neither caspase-3 (expression and activity) nor Bcl(2) positively immunostained cells were affected by INGAP-PP. Accordingly, INGAP-PP would promote stem cell differentiation into a beta-like cell phenotype, simultaneously decreasing its differentiation toward non-beta-cell precursors. Therefore, INGAP-PP would be potentially useful to obtain beta-cells from stem cells for replacement therapy. PMID:19159649

  10. 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

  11. 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

  12. Effects of Alcohol on the Regulation of Imprinted Genes in Mouse Stem Cells 

    E-print Network

    Crocker, Alyssa

    2013-02-04

    ABSTRACT Effects of Alcohol on the Regulation of Imprinted Genes in Mouse Stem Cells. (December 2013) Alyssa Crocker Department of Animal Science Texas A&M University Research Advisor: Dr. Michael Golding Department of Veterinary Physiology...

  13. Effects of Alcohol on the Regulation of Imprinted Genes in Mouse Stem Cells

    E-print Network

    Crocker, Alyssa

    2013-02-04

    ABSTRACT Effects of Alcohol on the Regulation of Imprinted Genes in Mouse Stem Cells. (December 2013) Alyssa Crocker Department of Animal Science Texas A&M University Research Advisor: Dr. Michael Golding Department of Veterinary Physiology...

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

    PubMed

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

    2007-11-01

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

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

    Microsoft Academic Search

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

    2010-01-01

    Stem cells display sensitivity to substrate presentation of topographical cues via changes in cell morphology. These biomechanical responses may be transmitted to the nucleus through cytoskeletal-linked signaling pathways. Here we investigate the influence of aligned substratum topography on the cell morphology and subsequently, the neuronal differentiation capabilities of adult neural stem cells (ANSCs). ANSCs that were cultured on aligned fibers

  16. 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

  17. 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

  18. Stem Cell Biology

    Microsoft Academic Search

    Elizabeth O. Hexner; Stephen G. Emerson

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

  19. 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.

  20. Graphene based scaffolds effects on stem cells commitment.

    PubMed

    Bressan, Eriberto; Ferroni, Letizia; Gardin, Chiara; Sbricoli, Luca; Gobbato, Luca; Ludovichetti, Francesco Saverio; Tocco, Ilaria; Carraro, Amedeo; Piattelli, Adriano; Zavan, Barbara

    2014-01-01

    Graphene is a flat monolayer of carbon atoms, arranged in a two-dimensional hexagonal structure, with extraordinary electrical, thermal, and physical properties. Moreover, the molecular structure of graphene can be chemically modified with molecules of interest to promote the development of high-performance devices. Although carbon derivatives have been extensively employed in industry and electronics, their use in regenerative medicine is still in an early phase. Study prove that graphene is highly biocompatible, has low toxicity and a large dosage loading capacity. This review describes the ability of graphene and its related materials to induce stem cells differentiation into osteogenic, neuronal, and adipogenic lineages. PMID:25344443

  1. 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

  2. Stemming the Stem Cell Setback

    Microsoft Academic Search

    Patrick J. Fleis

    2003-01-01

    This Comment highlights the recent federal funding setbacks in the biotechnology industry and considers the resulting challenges to future research collaboration. After providing a historical background to stem cell technology, Mr. Fleis examines the passionately opposed public responses to the technology's use of embryos and to its future applications. Fleis continues by noting past legislative initiatives that have accelerated the

  3. The effect of mesenchymal stem cell shape on the maintenance of multipotency Douglas Zhang, Kristopher A. Kilian*

    E-print Network

    Kilian, Kristopher A.

    The effect of mesenchymal stem cell shape on the maintenance of multipotency Douglas Zhang 2012 Accepted 10 February 2013 Available online 6 March 2013 Keywords: Mesenchymal stem cells Micropatterning Multipotency Differentiation Self-assembled monolayers a b s t r a c t Human mesenchymal stem

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

    PubMed

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

    2013-12-01

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

  5. Tracking adult stem cells

    Microsoft Academic Search

    Hugo J Snippert; Hans Clevers

    2011-01-01

    The maintenance of stem-cell-driven tissue homeostasis requires a balance between the generation and loss of cell mass. Adult stem cells have a close relationship with the surrounding tissue—known as their niche—and thus, stem-cell studies should preferably be performed in a physiological context, rather than outside their natural environment. The mouse is an attractive model in which to study adult mammalian

  6. 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.

  7. 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

  8. 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.

  9. Bioreactors Stem Cells

    E-print Network

    Schüler, 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

  10. 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

  11. Stem cells, colorectal cancer and cancer stem cell markers correlations.

    PubMed

    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

  12. Membrane Glycolipids in Stem Cells

    PubMed Central

    Yu, Robert K.; Suzuki, Yusuke; Yanagisawa, Makoto

    2015-01-01

    Stem cells, such as embryonic stem cells, hematopoietic stem cells, neural stem cells, mesenchymal stem cells, and very small embryonic-like stem cells, are undifferentiated cells that are endowed with a high potential for proliferation and the capacity for self-renewal with retention of pluri/multipotency to differentiate into their progenies. Recently, studies regarding the biological functions of glycolipids and cell surface microdomains (caveolae, lipid rafts, or glycolipid-enriched microdomains) in stem cells are emerging. In this review, we introduce the expression patterns of glycolipids and the functional roles of cell surface microdomains in stem cells. PMID:19716368

  13. An effective and safe supplement for stem cells expansion ex vivo: cord blood serum.

    PubMed

    Ma, Hai-ying; Yao, Li; Yu, Yan-qiu; Li, Li; Ma, Ling; Wei, Wen-juan; Lu, Xiao-mei; Du, Li-li; Jin, Yu-nan

    2012-01-01

    Mesenchymal stem cells (MSCs) are potential and optimal stem cells in clinical cell therapy, and fetal bovine serum (FBS) is widely used for expansion of MSCs, despite the risks of infectious disease transmission and immunological reaction of the xenogenic origin. This study was designed to compare human four blood group cord blood serum (CBS) with FBS in culturing human placenta-derived mesenchymal stem cells (hPDMSCs), which were derived from four blood group donors. The expansion medium included: 10% FBS, 10% A-CBS, 10% B-CBS, 10% O-CBS, and 10% AB-CBS. Cumulative population doubling, generation time, fold expansion rates and differentiation capacity, cell cycle, and immunophenotype were also assessed. The results showed that fold expansion rate and cumulative population doubling of hPDMSCs significantly increased during long-term MSC expansion in CBS medium, but the generation time decreased compared with FBS. CBS might be an effective supplement for stem cells expand rapidly ex vivo. Cell cycle and differentiation assays showed that most of the hPDMSCs expanding in the presence of CBS were in stationary phase, which was the characteristic of stem cells, and they retained their ability to differentiate into chondrogenic and endothelial cells. By comparing these four blood groups of CBS, we found that there was no significant difference among different blood groups in culturing hPDMSCs, which were isolated from different blood group donors. So CBS may be an optimal replacement to avoid the risks of FBS application in expansion of stem cell for clinical cell therapy and tissue engineering. PMID:22182982

  14. 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...

  15. Effect of Superparamagnetic Iron Oxide Nanoparticles-Labeling on Mouse Embryonic Stem Cells

    PubMed Central

    Parsa, Hamed; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadeh, Parvin; Amoghli Tabrizi, Bahram; Dehdilani, Nima; Lotfinegad, Parisa; Soleimanloo, Farzaneh

    2015-01-01

    Objective Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label mammalian cells and to monitor their fate in vivo using magnetic resonance imaging (MRI). However, the effectiveness of phenotype of labeled cells by SPIONs is still a matter of question. The aim of this study was to investigate the efficiency and biological effects of labeled mouse embryonic stem cells (mESCs) using ferumoxide- protamine sulfate complex. Materials and Methods In an experimental study, undifferentiated mESCs, C571 line, a generous gift of Stem Cell Technology Company, were cultured on gelatin-coated flasks. The proliferation and viability of SPION-labeled cells were compared with control. ESCs and embryoid bodies (EBs) derived from differentiated hematopoietic stem cells (HSCs) were analyzed for stage-specific cell surface markers using fluorescence-activated cell sorting (FACS). Results Our observations showed that SPIONs have no effect on the self-renewal ability of mESCs. Reverse microscopic observations and prussian blue staining revealed 100% of cells were labeled with iron particles. SPION-labeled mESCs did not significantly alter cell viability and proliferation activity. Furthermore, labeling did not alter expression of representative surface phenotypic markers such as stage-specific embryonic antigen 1 (SSEA1) and cluster of differentiation 117 (CD117) on undifferentiated ESC and CD34, CD38 on HSCs, as measured by flowcytometry. Conclusion According to the results of the present study, SPIONs-labeling method as MRI agents in mESCs has no negative effects on growth, morphology, viability, proliferation and differentiation that can be monitored in vivo, noninvasively. Noninvasive cell tracking methods are considered as new perspectives in cell therapy for clinical use and as an easy method for evaluating the placement of stem cells after transplantation. PMID:26199901

  16. ADULT MESENCHYMAL STEM CELLS DERIVED FROM EMBRYONIC STEM CELLS

    Microsoft Academic Search

    N. L. BOYD; P. BOSCH; S. L. STICE

    Mesenchymal stem cells (MSC) are useful in cell therapy and stem cell research but they have a limited lifespan in culture. Our goal was to develop a unique and limitless supply of mesenchymal stem cells derived from human embryonic stem cells, opening up new uses and enhance existing uses of these important cell types. For any application that uses large

  17. Effects of human yolk sac endothelial cells on supporting expansion of hematopoietic stem\\/progenitor cells from cord blood

    Microsoft Academic Search

    Liangshan Hu; Lamei Cheng; Jian Wang; Huiping Zhao; Huaxin Duan; Guangxiu Lu

    2006-01-01

    In order to investigate the effects of human yolk sac-derived endothelial cells (hYSECs) on the expansion of human hematopoietic stem\\/progenitor cells (HS\\/PCs) from umbilical cord blood (UCB) in vitro, we purified hYSEC-like cells from 4–5 week human yolk sacs, which were morphologically similar to endothelial cells and expressed CD31, CD144 and vWF characteristics of endothelial cells. Then we isolated CD34+

  18. Effects of transplanted bone marrow mesenchymal stem cells on the irradiated intestine of mice

    Microsoft Academic Search

    Jian Zhang; Jian-Feng Gong; Wei Zhang; Wei-Ming Zhu; Jie-Shou Li

    2008-01-01

    We investigated the potency of exogenous bone marrow mesenchymal stem cells (MSCs) to engraft into irradiated intestine, as\\u000a well as these cellseffects on radiation-induced enteric injury. MSCs from ?-Gal-transgenic mice were transplanted into C57BL\\/6J\\u000a recipient mice that received abdominal irradiation (13 Gy). At different time points, recipient intestines were examined for\\u000a the engraftment of donor-derived cells by immunofluorescence analysis. Additionally,

  19. Adult stem cell plasticity

    Microsoft Academic Search

    Richard Poulsom; Malcolm R. Alison; Stuart J. Forbes; Nicholas A. Wright

    2002-01-01

    Observations made in the last few years support the existence of pathways, in adult humans and rodents, that allow adult stem cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows adult stem cells, assumed, until now, to be committed to generating a fixed range of progeny, to switch, when they have been relocated, to make

  20. 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

  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. 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

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

    PubMed

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

    2014-01-01

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

  4. Moderate Exercise Mitigates the Detrimental Effects of Aging on Tendon Stem Cells

    PubMed Central

    Zhang, Jianying; Wang, James H-C.

    2015-01-01

    Aging is known to cause tendon degeneration whereas moderate exercise imparts beneficial effects on tendons. Since stem cells play a vital role in maintaining tissue integrity, in this study we aimed to define the effects of aging and moderate exercise on tendon stem/progenitor cells (TSCs) using in vitro and in vivo models. TSCs derived from aging mice (9 and 24 months) proliferated significantly slower than TSCs obtained from young mice (2.5 and 5 months). In addition, expression of the stem cell markers Oct-4, nucleostemin (NS), Sca-1 and SSEA-1 in TSCs decreased in an age-dependent manner. Interestingly, moderate mechanical stretching (4%) of aging TSCs in vitro significantly increased the expression of the stem cell marker, NS, but 8% stretching decreased NS expression. Similarly, 4% mechanical stretching increased the expression of Nanog, another stem cell marker, and the tenocyte-related genes, collagen I and tenomodulin. However, 8% stretching increased expression of the non-tenocyte-related genes, LPL, Sox-9 and Runx-2, while 4% stretching had minimal effects on the expression of these genes. In the in vivo study, moderate treadmill running (MTR) of aging mice (9 months) resulted in the increased proliferation rate of aging TSCs in culture, decreased lipid deposition, proteoglycan accumulation and calcification, and increased the expression of NS in the patellar tendons. These findings indicate that while aging impairs the proliferative ability of TSCs and reduces their stemness, moderate exercise can mitigate the deleterious effects of aging on TSCs and therefore may be responsible for decreased aging-induced tendon degeneration. PMID:26086850

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

    Microsoft Academic Search

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

    2009-01-01

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

  6. Effects of Long-Term Culture on Human Embryonic Stem Cell Aging

    PubMed Central

    Xie, Xiaoyan; Hiona, Asimina; Lee, Andrew Stephen; Cao, Feng; Huang, Mei; Li, Zongjin; Cherry, Athena

    2011-01-01

    In recent years, human embryonic stem (hES) cells have become a promising cell source for regenerative medicine. Although hES cells have the ability for unlimited self-renewal, potential adverse effects of long-term cell culture upon hES cells must be investigated before therapeutic applications of hES cells can be realized. Here we investigated changes in molecular profiles associated with young (<60 passages) and old (>120 passages) cells of the H9 hES cell line as well as young (<85 passages) and old (>120 passages) cells of the PKU1 hES cell line. Our results show that morphology, stem cell markers, and telomerase activity do not differ significantly between young and old passage cells. Cells from both age groups were also shown to differentiate into derivatives of all 3 germ layers upon spontaneous differentiation in vitro. Interestingly, mitochondrial dysfunction was found to occur with prolonged culture. Old passage cells of both the H9 and PKU1 lines were characterized by higher mitochondrial membrane potential, larger mitochondrial morphology, and higher reactive oxygen species content than their younger counterparts. Teratomas derived from higher passage cells were also found to have an uneven preference for differentiation compared with tumors derived from younger cells. These findings suggest that prolonged culture of hES cells may negatively impact mitochondrial function and possibly affect long-term pluripotency. PMID:20629482

  7. 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. PMID:25848170

  8. Stem Cells in Aging

    PubMed Central

    Yunis, Edmond J.; Zúńiga, Joaquin; Koka, Prasad S.; Husain, Zaheed; Romero, Viviana; Stern, Joel N.H.; Fridkis-Hareli, Masha

    2008-01-01

    Aging is a genetically programmed decline in the functional effectiveness of the organism. It is manifested by a collective group of changes in cells or organs that occur over the course of a lifespan, limiting the duration of life. Longevity usually refers to long-lived members of a population within species. Organs develop and can involute according to specific timetables. Such timetables correlate with a preordained proliferative capacity of cells mediated by cell and organ clocks. In this review, we discuss different aspects related to genetic and environmental factors that are involved in determining life span. We discuss the influence of ontogenic, genetic and environmental factors in aging. The genetic factors can be studied in embryonic stem cells (ESC) and in niches (microenvironments) of stem cells (SC) using cellular or experimental animal models. We discuss molecular mechanisms involving genes and proteins associated with death pathways, niches, or hubs, on longevity. Moreover, we also discuss genes and proteins, associated with death pathways, on longevity. Unraveling these mechanisms may further our understanding of human aging leading to development of therapeutic interventions with the potential of prolonging life. PMID:19030125

  9. 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 of pluripotency in embryonic stem cells (ESCs) (De Los Angeles et al., 2012) and, along with Klf4 and c the requirement of OCT4, SOX2, and NANOG in stem cell function (De Los Angeles et al., 2012), discrepancies

  10. 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

  11. Prostate cancer stem cells

    PubMed Central

    Lang, SH; Frame, FM; Collins, AT

    2009-01-01

    Despite the discovery over 60 years ago by Huggins and Hodges 1 that prostate cancers respond to androgen deprivation therapy, hormone-refractory prostate cancer remains a major clinical challenge. There is now mounting evidence that solid tumours originate from undifferentiated stem cell-like cells coexisting within a heterogeneous tumour mass that drive tumour formation, maintain tumour homeostasis and initiate metastases. This review focuses upon current evidence for prostate cancer stem cells, addressing the identification and properties of both normal and transformed prostate stem cells. PMID:19040209

  12. 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

  13. 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

  14. Effects of an endothelial cell-conditioned medium on the hematopoietic and endothelial differentiation of embryonic stem cells

    Microsoft Academic Search

    Xuan Sun; Lamei Cheng; Huaxin Duan; Guangxiu Lu

    2009-01-01

    We have examined the effect of mouse bone marrow endothelial cell-conditioned medium (mEC-CM) on hematopoietic and endothelial differentiation of mouse embryonic stem cells (mESCs). mEC-CM can efficiently promote the differentiation of mESCs into Flk+ cells and hematopoietic colony-forming cells. mEC-CM proved to be as potent as a cytokine cocktail comprised of VEGF, bFGF, IGF and EGF. After inducing mESCs with

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

    E-print Network

    Voldman, Joel

    on stem cells. (A) Microfluidic perfusion systems exhibit more defined shear stress profiles and consume) for a typical soluble factor (MW~20 kDa) secreted by mouse embryonic stem cells (mESCs) investigated EMBRYONIC STEM CELLS Y.C. Toh1 and J. Voldman1* 1 Massachusetts Institute of Technology, USA ABSTRACT Shear

  16. Stem cell niches in mammals

    Microsoft Academic Search

    Thimios A. Mitsiadis; Ornella Barrandon; Ariane Rochat; Yann Barrandon; Cosimo De Bari

    2007-01-01

    Stem cells safeguard tissue homeostasis and guarantee tissue repair throughout life. The decision between self-renewal and differentiation is influenced by a specialized microenvironment called stem cell niche. Physical and molecular interactions with niche cells and orientation of the cleavage plane during stem cell mitosis control the balance between symmetric and asymmetric division of stem cells. Here we highlight recent progress

  17. Disguising adult neural stem cells

    Microsoft Academic Search

    Cindi M Morshead; Derek van der Kooy

    2004-01-01

    A description of adult neural stem cells has remained somewhat elusive. With no unique and definitive markers to label stem cells in general, neural stem cells are difficult to identify definitively and one is forced to examine cell behavior — leading to the retrospective identification of a stem cell. The most prevalent view in the literature describes the adult forebrain

  18. [Cancer stem cells].

    PubMed

    Wieczorek, Katarzyna; Niewiarowska, Jolanta

    2012-01-01

    Cancer stem cell theory gains increasingly greater significance in the world of medicine. Numerous findings of scientific research in vivo and in vitro indicate that it is the population of undifferentiated, self-renewing cells which is responsible for recurrence of cancer and metastasis. Similarly to normal stem cells, cancer stem cells (CSC) function in the environment of the other cells of the organism, called the niche, where they receive signals for differentiation and proliferation processes. Disorders in the signaling pathways between CSC and the niche that result from e.g. acquired oncogenic mutations may lead to uncontrolled proliferation of stem cells, gaining independence from the primary niche or settling a new microenvironment. CSC are identified on the basis of specific markers - membrane proteins or cell enzymes. Methods based on the measurement of dye fluorescence (obtaining side population, SP) or fluorescence of the fluorophore conjugated with a monoclonal antibody directed against the specific CSC marker are used for isolation. A different method obtains morphologically miscellaneous clones by single cell cloning: holo-, mero- and paraclones. Tumor forming assay in NOD/SCID mice is a standard in vivo test that confirms the stem character of isolated cells. However, this model may not fully reflect the complexity of cancer illnesses in human beings. Solving the mystery of oncogenesis, including the existence of cancer stem cells, is undoubtedly one of the priorities of contemporary medicine that should contribute to the improvement of cancer therapy.  PMID:23001204

  19. 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,

  20. Stem Cells and Renal Regeneration

    Microsoft Academic Search

    C. Roufosse; H. T. Cook

    2008-01-01

    The role of embryonal or adult stem cells, in particular bone marrow (BM)-derived stem cells, in regenerating the kidney after injury has been the subject of intensive investigation. BM-derived stem cells have been shown to give rise to small numbers of most renal cell types, including tubular cells, mesangial cells, podocytes, vascular cells and interstitial cells. However, the role this

  1. Diabetes and Stem Cell Function

    PubMed Central

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

    2015-01-01

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

  2. Effects of paracrine factors on CD24 expression and neural differentiation of male germline stem cells.

    PubMed

    Kim, Bang-Jin; Lee, Yong-An; Kim, Ki-Jung; Kim, Yong-Hee; Jung, Mi-Seon; Ha, Seung-Jung; Kang, Hyun-Gu; Jung, Sang-Eun; Kim, Byung-Gak; Choi, Yu-Ri; Do, Jeong Tae; Ryu, Buom-Yong

    2015-07-01

    Spermatogonial stem cells (SSCs) are adult male germ cells that develop after birth. Throughout the lifetime of an organism, SSCs sustain spermatogenesis through self-renewal and produce daughter cells that differentiate into spermatozoa. Several studies have demonstrated that SSCs can acquire pluripotency under appropriate culture conditions, thus becoming multipotent germline stem cells (mGSCs) that express markers of pluripotency in culture and form teratomas following transplantation into immunodeficient mice. In the present study, we generated neural precursor cells expressing CD24, a neural precursor marker, from pluripotent stem cell lines and demonstrated that these cells effectively differentiated along a neural lineage in vitro. In addition, we found that paracrine factors promoted CD24 expression during the neural differentiation of mGSCs. Our results indicated that the expression of CD24, enhanced by a combination of retinoic acid (RA), noggin and fibroblast growth factor 8 (FGF8) under serum-free conditions promoted neural precursor differentiation. Using a simple cell sorting method, we were able to collect neural precursor cells with the potential to differentiate from mGSCs into mature neurons and astrocytes in vitro. PMID:25976705

  3. T-cell and natural killer cell therapies for hematologic malignancies after hematopoietic stem cell transplantation: enhancing the graft-versus-leukemia effect

    PubMed Central

    Cruz, C. Russell; Bollard, Catherine M.

    2015-01-01

    Hematopoietic stem cell transplantation has revolutionized the treatment of hematologic malignancies, but infection, graft-versus-host disease and relapse are still important problems. Calcineurin inhibitors, T-cell depletion strategies, and immunomodulators have helped to prevent graft-versus-host disease, but have a negative impact on the graft-versus-leukemia effect. T cells and natural killer cells are both thought to be important in the graft-versus-leukemia effect, and both cell types are amenable to ex vivo manipulation and clinical manufacture, making them versatile immunotherapeutics. We provide an overview of these immunotherapeutic strategies following hematopoietic stem cell transplantation, with discussions centered on natural killer and T-cell biology. We discuss the contributions of each cell type to graft-versus-leukemia effects, as well as the current research directions in the field as related to adoptive cell therapy after hematopoietic stem cell transplantation. PMID:26034113

  4. Cytosine deaminase-producing human mesenchymal stem cells mediate an antitumor effect in a mouse xenograft model

    Microsoft Academic Search

    Mi-Hyeon You; Wang-Joon Kim; Wooyoung Shim; Sang-Rim Lee; Gwang Lee; Sangdun Choi; Dae-Yong Kim; Yong Man Kim; Hyunsoo Kimand; Sang-Uk Han

    2009-01-01

    Background and Aim: Stem cell transplantation offers potential gene therapy for brain tumors. However, this approach has received little attention as a treatment for gastrointes- tinal tumors. In the present study, we explored the possibility of human bone marrow- derived mesenchymal stem cells (hMSC) producing cytosine deaminase (CD), followed by systemic 5-fluorocytosine (5-FC) administration, showing an antitumor effect on a

  5. 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

  6. Cancerous stem cells: deviant stem cells with cancer-causing misbehavior.

    PubMed

    Chandler, Julie M; Lagasse, Eric

    2010-01-01

    Stem cells maintain homeostasis in adult tissues via self-renewal and generation of terminally differentiated cells. Alterations in this intricate balance can result in disease. It has become increasingly evident that cancer can be initiated at the level of stem cells. Therefore, understanding what causes stem cells to become cancerous may lead to new therapeutic approaches. Multiple signaling pathways ultimately affect stem cell survival and proliferation, thus maintaining homeostasis in the gut. Changes in these pathways could perturb normal stem cell behavior, leading to cancerous stem cells. In addition, cancerous stem cells show resistance to current therapies and may lead to a dangerous selection process resulting in recurrence and metastasis. Genomic instability, the driving force of mutation and resistance, may give cancerous stem cells an adaptive advantage, especially when subjected to cancer therapies. Targeting the unique characteristics of cancerous stem cells to promote either terminal differentiation or destruction would effectively eradicate cancer and improve patient care and survival. PMID:20587011

  7. Effect of Stem Cell Therapy on Amiodarone Induced Fibrosing Interstitial Lung Disease in Albino Rat

    PubMed Central

    Zaglool, Somaya Saad; Zickri, Maha Baligh; Abd El Aziz, Dalia Hussein; Mabrouk, Doaa; Metwally, Hala Gabr

    2011-01-01

    Background and Objectives: The fibrosing forms of interstitial lung disease (ILD) are associated with significant morbidity and mortality. ILD may be idiopathic, secondary to occupational, infection, complicate rheumatic diseases or drug induced. Efficacy of antifibrotic agents is as far as, limited and uncertain. No effective treatment was confirmed for pulmonary fibrosis except lung transplantation. The present study aimed at investigating the possible effect of human cord blood mesenchymal stem cell (MSC) therapy on fibrosing ILD. This was accomplished by using amiodarone as a model of induced lung damage in albino rat. Methods and Results: Seventeen adult male albino rats were divided into 3 groups. Rats of amiodarone group were given 30 mg/kg of amiodarone orally 6 days/ week for 6 weeks. Rats of stem cell therapy group were injected with stem cells in the tail vein following confirmation of lung damage and left for 4 weeks before sacrifice. Obstructed bronchioles, thickened interalveolar septa and thickened wall of pulmonary vessels were found and proved morphometrically. Reduced type I pneumocytes and increased area% of collagen fibers were recorded. All findings regressed on stem cell therapy. Conclusions: Cord blood MSC therapy proved definite amelioration of fibrosing interstitial lung disease provided therapy starts early in the development of the pathogenesis. PMID:24298346

  8. 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

  9. 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

  10. 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

  11. Hormonal control of stem cell systems.

    PubMed

    Gancz, Dana; Gilboa, Lilach

    2013-01-01

    Many organs respond to physiological challenges by changing tissue size or composition. Such changes may originate from tissue-specific stem cells and their supportive environment (niche). The endocrine system is a major effector and conveyor of physiological changes and as such could alter stem cell behavior in various ways. In this review, we examine how hormones affect stem cell biology in four different organs: the ovary, intestine, hematopoietic system, and mammary gland. Hormones control every stage of stem cell life, including establishment, expansion, maintenance, and differentiation. The effects can be cell autonomous or non-cell autonomous through the niche. Moreover, a single hormone can affect different stem cells in different ways or affect the same stem cell differently at various developmental times. The vast complexity and diversity of stem cell responses to hormonal cues allow hormones to coordinate the body's reaction to physiological challenges. PMID:23875645

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

    Microsoft Academic Search

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

    2005-01-01

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

  13. 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.

  14. 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

  15. Hematopoietic Stem Cells

    Microsoft Academic Search

    Malcolm A. S. Moore

    \\u000a Hematopoietic stem cells (HSCs) are the most well-characterized tissue-specific stem cell. Over 50 years of basic research\\u000a and clinical application has provided insight into the molecular and cellular mechanisms of HSC biology. HSC undergo self-renewal\\u000a by symmetric or asymmetric division, or differentiation to common myeloid progenitors and progressively more differentiated\\u000a myeloid and lymphoid progeny. The chemokine SDF-1\\/ CXCL12 produced by

  16. Germline Stem Cells

    PubMed Central

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

    2011-01-01

    Sperm and egg production requires a robust stem cell system that balances self-renewal with differentiation. Self-renewal at the expense of differentiation can cause tumorigenesis, whereas differentiation at the expense of self-renewal can cause germ cell depletion and infertility. In most organisms, and sometimes in both sexes, germline stem cells (GSCs) often reside in a defined anatomical niche. Factors within the niche regulate a balance between GSC self-renewal and differentiation. Asymmetric division of the germline stem cell to form daughter cells with alternative fates is common. The exception to both these tendencies is the mammalian testis where there does not appear to be an obvious anatomical niche and where GSC homeostasis is likely accomplished by a stochastic balance of self-renewal and differentiation and not by regulated asymmetric cell division. Despite these apparent differences, GSCs in all organisms share many common mechanisms, although not necessarily molecules, to guarantee survival of the germline. PMID:21791699

  17. Encapsulated stem cells for cancer therapy

    PubMed Central

    2013-01-01

    Stem cells have inherent tumor?trophic migratory properties and can serve as vehicles for delivering effective, targeted therapy to isolated tumors and metastatic disease, making them promising anti?cancer agents. Encapsulation of therapeutically engineered stem cells in hydrogels has been utilized to provide a physical barrier to protect the cells from hostile extrinsic factors and significantly improve the therapeutic efficacy of transplanted stem cells in different models of cancer. This review aims to discuss the potential of different stem cell types for cancer therapy, various engineered stem cell based therapies for cancer, stem cell encapsulation process and provide an in depth overview of current applications of therapeutic stem cell encapsulation in the highly malignant brain tumor, glioblastoma multiforme (GBM), as well as the prospects for their clinical translation. PMID:23507920

  18. Encapsulated stem cells for cancer therapy.

    PubMed

    Shah, Khalid

    2013-01-01

    Stem cells have inherent tumor?trophic migratory properties and can serve as vehicles for delivering effective, targeted therapy to isolated tumors and metastatic disease, making them promising anti?cancer agents. Encapsulation of therapeutically engineered stem cells in hydrogels has been utilized to provide a physical barrier to protect the cells from hostile extrinsic factors and significantly improve the therapeutic efficacy of transplanted stem cells in different models of cancer. This review aims to discuss the potential of different stem cell types for cancer therapy, various engineered stem cell based therapies for cancer, stem cell encapsulation process and provide an in depth overview of current applications of therapeutic stem cell encapsulation in the highly malignant brain tumor, glioblastoma multiforme (GBM), as well as the prospects for their clinical translation. PMID:23507920

  19. Chip-based time-continuous monitoring of toxic effects on stem cell differentiation.

    PubMed

    Cho, Sungbo; Gorjup, Erwin; Thielecke, Hagen

    2009-01-01

    Pesticides used to control unwanted insects are potentially toxic to humans. In assessing the risk involved in exposure to pesticides or complex chemical mixtures, an in vitro cell-based test can provide useful information regarding danger to human health. Cell differentiation is a biological process of fundamental importance in developing and adult organisms. In this paper, we propose a cell-based test system for continuous, label-free monitoring of the effect of test substances on stem cell differentiation. Using a prefabricated electrode-based chip and impedance measurement system, we investigated the influence of chlorpyrifos (a pesticide) on the differentiation of human mesenchymal stem cells (hMSCs) to adipocytes. The state of hMSCs on electrodes during adipogenic differentiation or after application of the cytotoxic substance was clearly reflected in the impedance measurement. Chlorpyrifos caused a partially uncovered electrode area with a decreased number of lipid vacuoles, thus leading to a rapid decrease in resistance in the cell layer. After removal of the chlorpyrifos, the cell layer resistance was regained due to the renewed covering of the electrodes by hMSCs. However, an increase in lipid vacuoles was not observed. From this, it was concluded that the measured resistance of hMSCs is determined by the electrical properties in the extra cellular space (e.g., cell/electrode or cell/cell gap), but not by the lipid vacuoles appearing in intracellular space during adipogenic differentiation. PMID:19054659

  20. Challenges for heart disease stem cell therapy

    PubMed Central

    Hoover-Plow, Jane; Gong, Yanqing

    2012-01-01

    Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress. PMID:22399855

  1. Combination Cell Therapy with Mesenchymal Stem Cells and Neural Stem Cells for Brain Stroke in Rats

    PubMed Central

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-01-01

    Objectives Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. Method and Materials The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. Result The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. Conclusions The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats. PMID:26019759

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

    PubMed Central

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

    2012-01-01

    Background: Glioblastoma multiforme (GBM) cells are resistant to anticancer drugs. Cancer stem cells (CSCs) are a key mediator of chemoresistance. We have reported that disulfiram (DS), an aldehyde dehydrogenase (ALDH) inhibitor, targets breast CSC-like cells. In this study, the effect of DS and combination of DS and gemcitabine (dFdC) on GBM cells and GBM stem-like cells was investigated. Methods: 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI)-isobologram, western blot, luciferase reporter gene assay, electrophoretic mobility-shift assay and ALDH analysis were used in this study. Results: Disulfiram is cytotoxic in GBM cell lines in a copper (Cu)-dependent manner. Disulfiram/copper enhances the cytotoxicity of dFdC. Combination index-isobologram analysis indicates a synergistic effect between DS/Cu and dFdC. Disulfiram/copper induces reactive oxygen species (ROS), activates JNK and p38 pathways and inhibits nuclear factor-kappa B activity in GBM cell lines. Disulfiram/copper may trigger intrinsic apoptotic pathway via modulation of the Bcl2 family. Disulfiram/copper abolishes stem-like cell population in GBM cell lines. Conclusion: Our findings indicate that the cytotoxicity of DS/Cu and the enhancing effect of DS/Cu on the cytotoxicity of dFdC in GBM stem-like cells may be caused by induction of ROS and inhibition of both ALDH and the NFkB pathway. Both DS and dFdC can traverse the blood–brain barrier. Further study may lead them into GBM chemotherapy. PMID:23033007

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

    PubMed Central

    Zhang, Joy Yueyue

    2013-01-01

    In terms of stem cell research, China appears both as a “powerhouse” armed with state-of-the-art facilities, internationally trained personnel and permissive regulation and as a “bit player,” with its capability for conducting high quality research still in question. The gap between China’s assiduous endeavors and the observed outcome is due to a number of factors. Based on interviews with 48 key stakeholders active in Chinese stem cell research, this article examines how the structure of scientific institutions has affected effective governance in China. It is demonstrated that despite China’s recent efforts to attract highly competent researchers and to launch new regulatory initiatives, the effects of these attempts have been diminished by an absence of middle-layer positions within research teams and by the uncoordinated administrative structures among regulatory bodies. PMID:24143127

  4. Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells.

    PubMed

    Konyalioglu, Sibel; Armagan, Guliz; Yalcin, Ayfer; Atalayin, Cigdem; Dagci, Taner

    2013-02-25

    Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antioxidant effects of resveratrol against hydrogen peroxide in embryonic neural stem cells. Hydrogen peroxide treatment alone increased catalase and glutathione peroxidase activities but did not change superoxide dismutase levels compared with hydrogen peroxide + resveratrol treatment. Nitric oxide synthase activity and concomitant nitric oxide levels increased in response to hydrogen peroxide treatment. Conversely, resveratrol treatment decreased nitric oxide synthase activity and nitric oxide levels. Resveratrol also attenuated hydrogen peroxide-induced nuclear or mitochondrial DNA damage. We propose that resveratrol may be a promising agent for protecting embryonic neural stem cells because of its potential to decrease oxidative stress by inducing higher activity of antioxidant enzymes, decreasing nitric oxide production and nitric oxide synthase activity, and alleviating both nuclear and mitochondrial DNA damage. PMID:25206691

  5. 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.

  6. The Effect of Human Fetal Liver-Derived Mesenchymal Stem Cells on CD34 + Hematopoietic Stem Cell Repopulation in NOD\\/Shi-scid\\/IL2Ră null Mice

    Microsoft Academic Search

    H.-M. Yang; M.-R. Cho; J.-H. Sung; S.-J. Yang; M.-H. Nam; C.-R. Roh; J. M. Kim; M. Shin; S. H. Song; C.-H. Kwon; J.-W. Joh; S. J. Kim

    2011-01-01

    Mesenchymal stem cells (MSCs) are progenitors that are capable of differentiating into mesenchymal tissues. They are known to support allogeneic hematopoietic stem cell transplantation by facilitating engraftment without increasing the risk of graft-versus-host disease. We optimized culture conditions for human fetal liver-derived MSCs (hFL-MSCs) to investigate the role of hFL-MSCs on repopulation of hematopoietic stem cells in NOD\\/Shi-scid\\/IL-2R?null (NOG) mice

  7. 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, Canada *Correspondence: jellis@sickkids.ca (J.E.), william.stanford@utoronto.ca (W.L.S.) DOI 10.1016/j.stem

  8. A Preliminary Study of the Effects of Liposuction Technique on Adipose-Derived Stem Cell Viability

    Microsoft Academic Search

    Caitlyn Moore

    2011-01-01

    Adult stem cells possess the capability to differentiate into cells of many lineages. As such, they are ideal for use in tissue engineering and regenerative medicine purposes. Well-known sources of adult stem cells include bone marrow aspirate, but other sources have gained recognition in recent years. Studies have demonstrated that the adipose tissue recovered from liposuction can be a source

  9. Stem Cell Therapy for Heart Failure

    PubMed Central

    2013-01-01

    The last decade has witnessed the publication of a large number of clinical trials primarily using bone marrow-derived stem cells as the injected cell. These “first-generation” clinical trials have advanced our understanding and shown us that (1) cell therapy is safe, (2) cell therapy has been modestly effective, and (3) in humans, bone marrow-derived stem cells do not transdifferentiate into cardiomyocytes or new blood vessels (or at least in sufficient numbers to have any effect). The primary mechanism of action for cell therapy is now believed to be through paracrine effects that include the release of cytokines, chemokines, and growth factors that inhibit apoptosis and fibrosis, enhance contractility, and activate endogenous regenerative mechanisms through endogenous circulating or site-specific stem cells. The new direction for clinical trials includes the use of stem cells capable of cardiac lineage, such as endogenous cardiac stem cells. PMID:24298308

  10. 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

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

    PubMed

    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

  12. Splitting identities: The effects of religion, political identity, interest in science, and personal interest on attitudes about embryonic stem cell research

    Microsoft Academic Search

    Kristopher Harry Morgan

    2009-01-01

    My research takes up the question of the relative effects of religious identity, political identity, knowledge of science and stem cell research, and personal interest on attitudes towards science in general and embryonic stem cell research (ESCR) in particular. Structural equation modeling is used to construct associative models of attitudes towards stem cell research using data from the 2005 Virginia

  13. 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

  14. Stem Cells in Intraepithelial Neoplasia

    Microsoft Academic Search

    Nicholas A. Wright

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

  15. Controversies over stem cell research

    Microsoft Academic Search

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

    2003-01-01

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

  16. Investigation of the Effective Action Distance Between Hematopoietic Stem\\/Progenitor Cells and Human Adipose-Derived Stem Cells During Their In Vitro Co-culture

    Microsoft Academic Search

    Kedong Song; Hai Wang; Hong Wang; Ling Wang; Mo Qiao; Shuang Wu; Tianqing Liu

    The in vitro suitable action distance between umbilical cord blood-derived hematopoietic stem\\/progenitor cells and its feeder\\u000a cell, human adipose-derived stem cells, during their co-culture, was investigated through a novel transwell co-culture protocol,\\u000a in which the distance between the two culture chambers where each cell type is growing can be adjusted from 10 to 450 ?m.\\u000a The total cell number was determined

  17. Stem cells today: B1. Bone marrow stem cells

    Microsoft Academic Search

    RG Edwards

    2004-01-01

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

  18. 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

  19. Neural stem cells.

    PubMed

    Kennea, Nigel L; Mehmet, Huseyin

    2002-07-01

    Neural stem cells (NSCs) have the ability to self-renew, and are capable of differentiating into neurones, astrocytes and oligodendrocytes. Such cells have been isolated from the developing brain and more recently from the adult central nervous system. This review aims to provide an overview of the current research in this evolving area. There is now increasing knowledge of the factors controlling the division and differentiation of NSCs during normal brain development. In addition, the cues for differentiation in vitro, and the possibility of transdifferentiation are reviewed. The discovery of these cells in the adult brain has encouraged research into their role during neurogenesis in the normal mature brain and after injury. Lastly other sources of neural precursors are discussed, and the potential for stem cells to be used in cell replacement therapy for brain injury or degenerative brain diseases with a particular emphasis on cerebral ischaemia and Parkinson's disease. PMID:12115869

  20. Breast Cancer Stem Cells

    PubMed Central

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. Therapeutic effects of mesenchymal stem cell-derived microvesicles on pulmonary arterial hypertension in rats

    PubMed Central

    Chen, Jian-ying; An, Ran; Liu, Zhen-jun; Wang, Jin-ju; Chen, Shu-zhen; Hong, Mian-ming; Liu, Jing-hu; Xiao, Meng-yuan; Chen, Yan-fang

    2014-01-01

    Aim: Microvesicles (MVs) are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy. In this study, we investigated the therapeutic effects of mesenchymal stem cell (MSC) derived MVs (MSC-MVs) on pulmonary artery hypertension (PAH) in rats. Methods: MSC-MVs were isolated from rat bone marrow MSCs that were cultured in a serum-free conditioned medium. Transmission electron microscopy (TEM), flow cytometry and nanoparticle tracking analysis (NTA) were used to characterize the MVs. Adult SD rats were injected with monocrotaline (50 mg/kg, sc) to induce PAH. Three weeks later, the rats were intravenously injected with MSCs, MSC-MVs or saline for 2 weeks. At the end of treatments, the hemodynamic parameters and pathological right ventricular and pulmonary arterial remodeling were analyzed in each group. Results: The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm. Intravenous injection of MSC-MVs or MSCs significantly ameliorated the mean pulmonary artery pressure (mPAP) and mean right ventricle pressure (mRVP) in PAH rats. Furthermore, intravenous injection of MSC-MVs or MSCs significantly decreased the right ventricle (RV) hypertrophy and pulmonary arteriole area index (AI) and thickness index (TI) in PAH rats. Conclusion: Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy. PMID:25088001

  4. [Effects of different culture system of isolating and passage of sheep embryonic stem-like cells].

    PubMed

    Bai, Changming; Liu, Chousheng; Wang, Zhigang; Wang, Xinzhuang

    2008-07-01

    In this research, we use mouse embryonic fibroblasts as feeder layers. To eliminate the influence of serum and mouse embryonic stem cells (ESCs) conditioned medium (ESCCM) on self-renewal of sheep embryonic stem-like cells, knockout serum replacement (KSR) was used to replace serum, then supplanted with ESCCM for the isolation and cloning of sheep embryonic stem-like cells. We found when inner cell masses (ICMs) cultured in the control group with medium supplanted with fetal bovine serum (FBS), sheep ES-like cells could not survive for more than 3 passages. However, sheep embryonic stem-like cells could remain undifferentiated for 5 passages when cultured in the medium that FBS was substituted by KSR. The result indicates that KSR culture system was more suitable for the isolation and cloning of sheep embryonic stem-like cells compared to FBS culture system. Finally we applied medium with 15% KSR as basic medium supplanted with 40% ESCCM as a new culture system to isolate sheep embryonic stem-like cells, we found one embryonic stem-like cell line still maintained undifferentiating for 8 passages, which characterized with a normal and stable karyotype and high expression of alkaline phosphatase. These results suggest that it is suitable to culture sheep ICM in the new culture system with 15% KSR as basic medium and supplanted with 40% ESCCM, which indicated that mouse ES cells might secrete factors playing important roles in promoting sheep ES-like cells' self-renewal. PMID:18837407

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

    PubMed Central

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

    2013-01-01

    This study was performed to investigate the effects of extremely low frequency pulsed electromagnetic fields (ELF-PEMFs) on the proliferation and differentiation of human alveolar bone-derived mesenchymal stem cells (hABMSCs). Osteogenesis is a complex series of events involving the differentiation of mesenchymal stem cells to generate new bone. In this study, we examined not merely the effect of ELF-PEMFs on cell proliferation, alkaline phosphatase (ALP) activity, and mineralization of the extracellular matrix but vinculin, vimentin, and calmodulin (CaM) expressions in hABMSCs during osteogenic differentiation. Exposure of hABMSCs to ELF-PEMFs increased proliferation by 15% compared to untreated cells at day 5. In addition, exposure to ELF-PEMFs significantly increased ALP expression during the early stages of osteogenesis and substantially enhanced mineralization near the midpoint of osteogenesis within 2 weeks. ELF-PEMFs also increased vinculin, vimentin, and CaM expressions, compared to control. In particular, CaM indicated that ELF-PEMFs significantly altered the expression of osteogenesis-related genes. The results indicated that ELF-PEMFs could enhance early cell proliferation in hABMSCs-mediated osteogenesis and accelerate the osteogenesis. PMID:23862141

  6. The Effect of Human Chorionic Gonadotropin Treatment on Recipient Mouse Germ Cell Proliferation Following Spermatogonial Stem Cell Transplantation of Neonatal Donor Mice

    PubMed Central

    Akhondi, Mohammad Mehdi; Najar, Reza Akbarzadeh; Jeddi-Tehrani, Mahmood; Sadeghi, Mohammad-Reza; Zarnani, Amir Hassan; Rabbani, Hodjattallah; Salehkhou, Sheida; Eini, Leila; Hoseinzadeh, Fatemeh; Heidari, Mahnaz

    2010-01-01

    Spermatogonia are the male germ line stem cells whose life long expansion is needed for permanent production of spermatozoa. The present study was designed to examine the effect of hCG treatment on germ cell proliferation following stem cell transplantation in mice. Spermatogonial stem cells were isolated from neonatal mice testes and characterized by alkaline phosphatase, immunoreactivity and morphological analysis. hCG was injected into normal and cell transplanted mice. We then evaluated the testosterone levels and cell number in normal mice. After that, cyclin B1 gene expression was investigated in transplanted mice. Different doses of busulfan were injected to investigate the effects of chemotherapy on morphological criteria and preparation of recipient mice for transplantation. In this report we show proliferative potential of spermatogonial stem cells after cytotoxic treatment, transplantation efficiency by semi-quantitative RT-PCR, and hCG effect on stem cell regeneration in normal mice and following cell transplantation. The results indicate that spermatogonial stem cells can proliferate after transplantation, and the efficiency of their transplantation depends on hormonal treatment. Therefore, hormonal treatment after stem cell transplantation will be a powerful avenue for increasing the efficiency of transplantation and fertility restoration. PMID:23407454

  7. [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

  8. 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

  9. Miscreant myeloproliferative disorder stem cells

    Microsoft Academic Search

    C H M Jamieson; C F Barroga; W P Vainchenker; CHM Jamieson

    2008-01-01

    Myeloproliferative disorders (MPDs), typified by robust marrow and extramedullary hematopoiesis, have a propensity to progress to acute leukemia. Although the hematopoietic stem cell (HSC) origin of MPDs was suggested over 30 years ago, only recently the HSC-specific effects of MPD molecular mutations have been investigated. The pivotal role of BCR-ABL in chronic myeloid leukemia (CML) development provided the rationale for

  10. Effects of nanostructures and mouse embryonic stem cells on in vitro morphogenesis of rat testicular cords.

    PubMed

    Pan, Fei; Chi, Lifeng; Schlatt, Stefan

    2013-01-01

    Morphogenesis of tubular structures is a common event during embryonic development. The signals providing cells with topographical cues to define a cord axis and to form new compartments surrounded by a basement membrane are poorly understood. Male gonadal differentiation is a late event during organogenesis and continues into postnatal life. The cellular changes resemble the mechanisms during embryonic life leading to tubular structures in other organs. Testicular cord formation is dependent on and first recognized by SRY-dependent aggregation of Sertoli cells leading to the appearance of testis-specific cord-like structures. Here we explored whether testicular cells use topographical cues in the form of nanostructures to direct or stimulate cord formation and whether embryonic stem cells (ES) or soluble factors released from those cells have an impact on this process. Using primary cell cultures of immature rats we first revealed that variable nanogratings exerted effects on peritubular cells and on Sertoli cells (at less than <1000 cells/mm(2)) by aligning the cell bodies towards the direction of the nanogratings. After two weeks of culture testicular cells assembled into a network of cord-like structures. We revealed that Sertoli cells actively migrate towards existing clusters. Contractions of peritubular cells lead to the transformation of isolated clusters into cord-like structures. The addition of mouse ES cells or conditioned medium from ES cells accelerated this process. Our studies show that epithelial (Sertoli cell) and mesenchymal (peritubular cells) cells crosstalk and orchestrate the formation of cords in response to physical features of the underlying matrix as well as secretory factors from ES cells. We consider these data on testicular morphogenesis relevant for the better understanding of mechanisms in cord formation also in other organs which may help to create optimized in vitro tools for artificial organogenesis. PMID:23555881

  11. 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

  12. Cell Stem Cell Patient-Specific Pluripotent Stem Cells

    E-print Network

    Collins, James J.

    Yamanaka1,2,* 1Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan: yamanaka@cira.kyoto-u.ac.jp DOI 10.1016/j.stem.2010.06.009 In this issue of Cell Stem Cell, Staerk et al and ethical issues regarding the usage of human embryos (Yamanaka, 2009). Patient-specific iPSCs, especially

  13. Stem Cell Interaction with Topography

    Microsoft Academic Search

    Benjamin K. K. Teo; Soneela Ankam; Evelyn K. F. Yim

    \\u000a The growth and differentiation of stem cells are regulated by biochemical and biophysical cues in the extracellular microenvironment.\\u000a Increasing evidences have shown that substrate topography, one of the biophysical properties of the microenvironment, can\\u000a affect stem cell fate, such as the maintenance of embryonic stem cells and the differentiation of adult and embryonic stem\\u000a cells. The underlying mechanism of how

  14. Microtechnology for Stem Cell Culture

    Microsoft Academic Search

    Elena Serena; Elisa Cimetta; Camilla Luni; Nicola Elvassore

    \\u000a Advances in stem cell research in recent decades have been aided by progress in the development of novel technologies aimed\\u000a at biological systems. At the same time mimicking stem cell niches in vitro has become crucial for both basic stem cell research\\u000a and the development of innovative therapies based on stem cells. Innovative microscale technologies can contribute to our\\u000a quantitative

  15. Materials as stem cell regulators

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

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

    Microsoft Academic Search

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

    2001-01-01

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

  17. 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.

  18. Stem cells find their niche

    Microsoft Academic Search

    Allan Spradling; Daniela Drummond-Barbosa; Toshie Kai

    2001-01-01

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

  19. The effects of poly L-lactic acid nanofiber scaffold on mouse spermatogonial stem cell culture

    PubMed Central

    Eslahi, Neda; Hadjighassem, Mahmoud Reza; Joghataei, Mohammad Taghi; Mirzapour, Tooba; Bakhtiyari, Mehrdad; Shakeri, Malak; Pirhajati, Vahid; Shirinbayan, Peymaneh; Koruji, Morteza

    2013-01-01

    Introduction A 3D-nanofiber scaffold acts in a similar way to the extracellular matrix (ECM)/basement membrane that enhances the proliferation and self-renewal of stem cells. The goal of the present study was to investigate the effects of a poly L-lactic acid (PLLA) nanofiber scaffold on frozen-thawed neonate mouse spermatogonial stem cells (SSCs) and testis tissues. Methods The isolated spermatogonial cells were divided into six culture groups: (1) fresh spermatogonial cells, (2) fresh spermatogonial cells seeded onto PLLA, (3) frozen-thawed spermatogonial cells, (4) frozen-thawed spermatogonial cells seeded onto PLLA, (5) spermatogonial cells obtained from frozen-thawed testis tissue, and (6) spermatogonial cells obtained from frozen-thawed testis tissue seeded onto PLLA. Spermatogonial cells and testis fragments were cryopreserved and cultured for 3 weeks. Cluster assay was performed during the culture. The presence of spermatogonial cells in the culture was determined by a reverse transcriptase polymerase chain reaction for spermatogonial markers (Oct4, GFR?-1, PLZF, Mvh(VASA), Itg?6, and Itg?1), as well as the ultrastructural study of cell clusters and SSCs transplantation to a recipient azoospermic mouse. The significance of the data was analyzed using the repeated measures and analysis of variance. Results The findings indicated that the spermatogonial cells seeded on PLLA significantly increased in vitro spermatogonial cell cluster formations in comparison with the control groups (culture of SSCs not seeded on PLLA) (P?0.001). The viability rate for the frozen cells after thawing was 63.00% ± 3.56%. This number decreased significantly (40.00% ± 0.82%) in spermatogonial cells obtained from the frozen-thawed testis tissue. Both groups, however, showed in vitro cluster formation. Although the expression of spermatogonial markers was maintained after 3 weeks of culture, there was a significant downregulation for some spermatogonial genes in the experimental groups compared with those of the control groups. Furthermore, transplantation assay and transmission electron microscopy studies suggested the presence of SSCs among the cultured cells. Conclusion Although PLLA can increase the in vitro cluster formation of neonate fresh and frozen-thawed spermatogonial cells, it may also cause them to differentiate during cultivation. The study therefore has implications for SSCs proliferation and germ cell differentiation in vitro. PMID:24348035

  20. Melanocytes, melanocyte stem cells, and melanoma stem cells

    PubMed Central

    Lang, Deborah; Mascarenhas, Joseph B.; Shea, Christopher R.

    2012-01-01

    Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, while the latter play an active role in a lethal form of cancer. These two cell types share several features and can be studied by similar methods. Aspects held in common by both melanocyte stem cells and melanoma stem cells include their expression of shared biochemical markers, a system of similar molecular signals necessary for their maintenance, and a requirement for an ideal niche microenvironment for providing these factors. This review provides a perspective of both these cell types and discusses potential models of stem cell growth and propagation. Recent findings provide a strong foundation for the development of new therapeutics directed at isolating and manipulating melanocyte stem cells for tissue engineering or at targeting and eradicating melanoma specifically, while sparing non-tumor cells. PMID:23438380

  1. 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

  2. The therapeutic effect of human adult stem cells derived from adipose tissue in endotoxemic rat model.

    PubMed

    Shin, Soyoung; Kim, Yonggoo; Jeong, Sikyoung; Hong, Sungyoup; Kim, Insoo; Lee, Woonjeong; Choi, Seungphil

    2013-01-01

    Excessive systemic inflammation following sepsis, trauma or burn could lead to multi-organ damage and death. Bone marrow stromal cells (BMSCs), commonly referred to as mesenchymal stem cells (MSCs), has been studied in several immune-associated diseases in human and animal by modulating the inflammatory response. Adipose tissue derived mesenchymal stem cells (ATSCs), which can be obtained more easily, compared with BMSCs, has emerged as an attractive alternative MSCs source for cell therapy. We investigated the therapeutic effects of human ATSCs (hATSCs) in endotoxemic rat model and their capacity to modulate the inflammatory response. Endotoxemia was induced with Lipopolysaccaride intravenously injection (LPS, 10mg/kg). Animals were divided into the following three groups: (1) saline + saline (n=5), (2) LPS + saline (n=5) and (3) LPS + hATSCs (2x10(6)) (n=5). The administration of LPS caused a consistent systemic inflammatory responses, increased concentrations of the pro-inflammatory cytokines that have an important role in sepsis. Treatment of endotoxemia with hATSCs decreased the level of inflammatory cytokines both in serum and in the lung, reduced inflammatory changes in the lung, prevented apoptosis in the kidney and improved multi-organ injury. In conclusion, our data demonstrates that hATSCs regulate the immue/inflammatory responses and improve multi-organ injury and they could be attractive candidates for cell therapy to treat endotoxemia. PMID:23289000

  3. 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

  4. Normal Stem Cells and Cancer Stem Cells: The Niche Matters

    Microsoft Academic Search

    Linheng Li; William B. Neaves

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

  5. [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

  6. Effect of the WWOX gene on the regulation of the cell cycle and apoptosis in human ovarian cancer stem cells.

    PubMed

    Yan, Hongchao; Tong, Jianye; Lin, Xiaoman; Han, Qiuyu; Huang, Hongxiang

    2015-08-01

    In order to examine new ideas for gene therapy in ovarian cancer, the specific mechanism underlying the effects of the WW domain containing oxidoreductase (WWOX) gene on cell cycle regulation and apoptosis in human ovarian cancer stem cells was investigated. Ovarian cancer stem cells were transfected with a eukaryotic expression vector carrying the WWOX gene in vitro (recombinant plasmid) and cells transfected with the empty plasmid (empty plasmid) or untransfected cells were used as controls. Stably transfected cells were screened and amplified in culture and the WWOX protein was detected by western blot analysis in the three groups of cells. Western blot analysis was performed to detect the expression of cell cycle regulatory proteins cyclin E, cyclin?dependent kinase (CDK) 2, cyclin D1, CDK4 and apoptosis?related protein Wnt?5? and c?Jun N?terminal kinase (JNK), while polymerase chain reaction (PCR) was used to detect alterations in the mRNA expression levels of caspase?3. The results demonstrated that the WWOX protein was stably expressed in cells of the recombinant plasmid group, but was not detected in cells of the empty plasmid group and the control group. Cell proliferation at each time point decreased significantly in the recombinant plasmid group compared with the empty plasmid group and the control group. Flow cytometric analysis demonstrated that the proportion of cells in the G0/G1 phase in the recombinant plasmid group was significantly higher than that of cells in the empty plasmid group and the control group. The rate of apoptosis in the recombinant plasmid group was significantly higher than that of cells in the empty plasmid group and the control group. Western blot analysis demonstrated that the expression levels of cyclin E, CDK2, cyclin D1 and CDK4 in the recombinant plasmid group were significantly lower than those in the empty plasmid group and the control group; however, the expression levels of Wnt?5? and JNK were significantly higher than those in the empty plasmid group and the control group. PCR results demonstrated that the mRNA expression level of caspase?3 in the recombinant plasmid group was significantly higher than that in the empty plasmid group and the control group. In conclusion, the present study demonstrated that the WWOX gene can be stably expressed in ovarian cancer stem cells and that it inhibits the proliferation of ovarian cancer stem cells. The WWOX gene can downregulate the expression levels of cell cycle proteins cyclin E?CDK2 and cyclin D1?CDK4, which affects the cell cycle of ovarian cancer stem cells. Furthermore, the WWOX gene can upregulate the mRNA expression levels of Wnt?5?, JNK and caspase?3, thus contributing to apoptosis of ovarian cancer stem cells. The present study demonstrated that the WWOX gene may be an important molecular target for the treatment of ovarian cancer in the future. PMID:25891642

  7. Side population cells separated from A549 lung cancer cell line possess cancer stem cell-like properties and inhibition of autophagy potentiates the cytotoxic effect of cisplatin.

    PubMed

    Yang, Yang; Fan, Yuxia; Qi, Yu; Liu, Donglei; Wu, Kai; Wen, Fengbiao; Zhao, Song

    2015-08-01

    Recent studies have suggested that cancer stem cells (CSCs) may be responsible for tumorigenesis and contribute to resistance to chemotherapy. Side population (SP) cells are thought to be enriched for CSCs in most types of human tumors. Therefore, the aim of the present study was to sort SP cells using an A549 lung cancer cell line, identify the cancer stem cell-like properties of SP and determine the role of autophagy in the survival of SP cells of lung cancer. SP cells were isolated by fluorescence-activated cell sorter (FACS) from A549 lung cancer cells, and the CSC-like properties were verified through confocal fluorescence imaging, sphere formation assays, cell proliferation and colony formation assay, gene expression in vitro and tumor formation in vivo. ?he role of autophagy in the survival of SP cells was assessed by western blotting and flow cytometric analysis. A549 lung cancer cells contained 1.10% SP cells. SP cells showed higher abilities of sphere and colony formation, cell proliferation and self-renewal. Moreover, compared to non-SP, SP cells demonstrated a higher mRNA expression of stem cell markers (MDR1, ABCG2 and OCT-4). The clone formation efficiency of SP cells was significantly higher than that non-SP cells under the same conditions. Expression of autophagosomes in SP cells was markedly lower than that in non-SP cells. However, the level of autophagy in SP cells was found to be markedly increased in the presence of cisplatin. In addition, inhibition of autophagy enhanced the effects of apoptosis induced by cisplatin. SP cells from the A549 lung cancer cell line possessed the properties of CSCs and were used to investigate the further characteristics of lung CSCs. SP cells were more resistant to chemotherapy and inhibition of autophagy enhanced the effects of apoptosis induced by the chemotherapeutic agent, cisplatin. These results may provide insight into novel therapeutic targets. PMID:26081992

  8. 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, UK *Correspondence: phj20@hutchison-mrc.cam.ac.uk DOI 10.1016/j.stem.2007.09.014 For the past 30

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

    PubMed

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

    2013-01-01

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

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

    SciTech Connect

    Li Yuming; Schilling, Tatjana; Benisch, Peggy; Zeck, Sabine; Meissner-Weigl, Jutta; Schneider, Doris [Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, D-97074 Wuerzburg (Germany); Limbert, Catarina [Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, D-97074 Wuerzburg (Germany); Division of Endocrinology and Diabetes, University of Freiburg (Germany); Seufert, Jochen [Division of Endocrinology and Diabetes, University of Freiburg (Germany); Kassem, Moustapha [Department of Endocrinology, University Hospital of Odense, Odense (Denmark); Schuetze, Norbert [Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, D-97074 Wuerzburg (Germany); Jakob, Franz [Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, D-97074 Wuerzburg (Germany)], E-mail: f-jakob.klh@mail.uni-wuerzburg.de; Ebert, Regina [Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, D-97074 Wuerzburg (Germany)

    2007-11-09

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

  11. Marrow Stromal Mesenchymal Stem Cells

    Microsoft Academic Search

    Cynthia B. Ripoll; Bruce A. Bunnell

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

  12. Therapeutic effect of adipose-derived mesenchymal stem cell injection in horses suffering from bone spavin.

    PubMed

    Nicpo?, J; Marycz, K; Grzesiak, J

    2013-01-01

    In this article we demonstrate the efficiency of autologous transplantations of adipose-derived mesenchymal stem cells for equine bone spavin treatment. Horses qualified to the study were divided into three groups: (i) research - treated with intra-articular injections of autologous stem cells, (ii) comparison treated with steroid drugs and (iii) control - untreated. All animals underwent comprehensive clinical examination before and after treatment. Our research confirms the long-term beneficial influence resulting from stem cell therapy in horse bone spavin treatment, in contrast to routine steroid usage. PMID:24597313

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

    PubMed

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

    2014-10-01

    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 × 10(5)/?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

  14. 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

  15. Adult skeletal muscle stem cells.

    PubMed

    Sambasivan, Ramkumar; Tajbakhsh, Shahragim

    2015-01-01

    Skeletal muscles in vertebrates have a phenomenal regenerative capacity. A muscle that has been crushed can regenerate fully both structurally and functionally within a month. Remarkably, efficient regeneration continues to occur following repeated injuries. Thousands of muscle precursor cells are needed to accomplish regeneration following acute injury. The differentiated muscle cells, the multinucleated contractile myofibers, are terminally withdrawn from mitosis. The source of the regenerative precursors is the skeletal muscle stem cells-the mononucleated cells closely associated with myofibers, which are known as satellite cells. Satellite cells are mitotically quiescent or slow-cycling, committed to myogenesis, but undifferentiated. Disruption of the niche after muscle damage results in their exit from quiescence and progression towards commitment. They eventually arrest proliferation, differentiate, and fuse to damaged myofibers or make de novo myofibers. Satellite cells are one of the well-studied adult tissue-specific stem cells and have served as an excellent model for investigating adult stem cells. They have also emerged as an important standard in the field of ageing and stem cells. Several recent reviews have highlighted the importance of these cells as a model to understand stem cell biology. This chapter begins with the discovery of satellite cells as skeletal muscle stem cells and their developmental origin. We discuss transcription factors and signalling cues governing stem cell function of satellite cells and heterogeneity in the satellite cell pool. Apart from satellite cells, a number of other stem cells have been shown to make muscle and are being considered as candidate stem cells for amelioration of muscle degenerative diseases. We discuss these "offbeat" muscle stem cells and their status as adult skeletal muscle stem cells vis-a-vis satellite cells. The ageing context is highlighted in the concluding section. PMID:25344672

  16. 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

  17. ``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

  18. Stem cell quest.

    PubMed

    Irvine, Alexandra

    2015-03-01

    Chronic Myeloid Leukaemia has been a valuable model system for experimental haematologists for many years. Virtually all patients (>95 %) have the same genetic change which has driven the development of the first targeted therapies, tyrosine kinase inhibitors (TKIs). Since the introduction of TKIs in 2000 it has become clear that this approach has significantly improved the outcome for these patients. Nevertheless drug resistance inevitably develops and it is clear that the disease is controlled rather than eradicated. The recent publication by Herrmann et al. has defined a sub-population of leukaemic stem cells which are responsible for propagating the disease. CD26 now provides a new specific target for the malignant stem cells and offers the possibility of true curative therapy. PMID:25698663

  19. An acute negative bystander effect of ?-irradiated recipients on transplanted hematopoietic stem cells

    PubMed Central

    Shen, Hongmei; Yu, Hui; Liang, Paulina H.; Cheng, Haizi; XuFeng, Richard; Yuan, Youzhong; Zhang, Peng; Smith, Clayton A.

    2012-01-01

    Ultimate success of hematopoietic stem cell transplantation (HSCT) depends not only on donor HSCs themselves but also on the host environment. Total body irradiation is a component in various host conditioning regimens for HSCT. It is known that ionizing radiation exerts “bystander effects” on nontargeted cells and that HSCs transplanted into irradiated recipients undergo proliferative exhaustion. However, whether irradiated recipients pose a proliferation-independent bystander effect on transplanted HSCs is unclear. In this study, we found that irradiated mouse recipients significantly impaired the long-term repopulating ability of transplanted mouse HSCs shortly (? 17 hours) after exposure to irradiated hosts and before the cells began to divide. There was an increase of acute cell death associated with accelerated proliferation of the bystander hematopoietic cells. This effect was marked by dramatic down-regulation of c-Kit, apparently because of elevated reactive oxygen species. Administration of an antioxidant chemical, N-acetylcysteine, or ectopically overexpressing a reactive oxygen species scavenging enzyme, catalase, improved the function of transplanted HSCs in irradiated hosts. Together, this study provides evidence for an acute negative, yet proliferation-independent, bystander effect of irradiated recipients on transplanted HSCs, thereby having implications for HSCT in both experimental and clinical scenarios in which total body irradiation is involved. PMID:22374698

  20. An acute negative bystander effect of ?-irradiated recipients on transplanted hematopoietic stem cells.

    PubMed

    Shen, Hongmei; Yu, Hui; Liang, Paulina H; Cheng, Haizi; XuFeng, Richard; Yuan, Youzhong; Zhang, Peng; Smith, Clayton A; Cheng, Tao

    2012-04-12

    Ultimate success of hematopoietic stem cell transplantation (HSCT) depends not only on donor HSCs themselves but also on the host environment. Total body irradiation is a component in various host conditioning regimens for HSCT. It is known that ionizing radiation exerts "bystander effects" on nontargeted cells and that HSCs transplanted into irradiated recipients undergo proliferative exhaustion. However, whether irradiated recipients pose a proliferation-independent bystander effect on transplanted HSCs is unclear. In this study, we found that irradiated mouse recipients significantly impaired the long-term repopulating ability of transplanted mouse HSCs shortly (? 17 hours) after exposure to irradiated hosts and before the cells began to divide. There was an increase of acute cell death associated with accelerated proliferation of the bystander hematopoietic cells. This effect was marked by dramatic down-regulation of c-Kit, apparently because of elevated reactive oxygen species. Administration of an antioxidant chemical, N-acetylcysteine, or ectopically overexpressing a reactive oxygen species scavenging enzyme, catalase, improved the function of transplanted HSCs in irradiated hosts. Together, this study provides evidence for an acute negative, yet proliferation-independent, bystander effect of irradiated recipients on transplanted HSCs, thereby having implications for HSCT in both experimental and clinical scenarios in which total body irradiation is involved. PMID:22374698

  1. Spermatogonial Stem Cells

    Microsoft Academic Search

    Dirk G. de Rooij

    \\u000a New developments in the field of spermatogonial stem cell (SSC) research have been reviewed. Novel techniques have rendered\\u000a interesting results in studies on SSC kinetics in nonprimate mammals as well as in primates, and the classical views on the\\u000a nature and the behavior of SSC are being challenged. However, no definite conclusions can yet be drawn. Many new proteins\\u000a have

  2. Toxicity effects of methamphetamine on embryonic stem cell-derived neuron

    PubMed Central

    Meamar, Rokhsareh; Dehghani, Leila; Karamali, Freshte

    2012-01-01

    Background: Methamphetamine (MA) is the most popular recreational drug. According to potential neurotoxicity of this agent, it can cause deleterious effects on neural differentiation of embryo, if MA is used during the child bearing period. In recent decades, undifferentiated pluripotent embryo-derived stem cell lines, resembling early embryonic stages, have been used to analyze the toxic effects of components in vitro. Thus, this study aims at assessing toxic effects of MA on embryonic stem cell (ESC)-derived neuronal cells during differentiation in a pharmacological model. Materials ans Methods: ESC line Royan was used throughout this study. The effect of MA on neural differentiation was assessed during two periods, group 1: MA (10, 100, 200,500, 750, 1000 ?M concentrations) was added during EB formation, group 2: MA (10, 50, 70, 100, 200, 500 ?M concentrations) was added after the generation of neural precursors. Then cells were evaluated for neuronal markers by immunocytochemistry and RT-PCR. One way ANOVA followed by the post hoc test was used to analyze data. Results: The declining in outgrowth of dendrites was observed in neural morphology in a dose dependent manner. The ID50 (Inhibition of neuronal differentiation) of groups 1 and 2 were 130 and 400 ?M, respectively. By using RT-PCR, in comparison with MAP2, no significant change was observed in Nestin expression. Conclusions: Our data on neuronal toxicity were consistent with in vivo and in vitro studies. We concluded that ESCs can be used as an efficient model to assess the toxicity of drugs. PMID:23626614

  3. 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

  4. 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

  5. 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.

  6. Generation of skeletal muscle stem/progenitor cells from murine induced pluripotent stem cells.

    PubMed

    Mizuno, Yuta; Chang, Hsi; Umeda, Katsutsugu; Niwa, Akira; Iwasa, Toru; Awaya, Tomonari; Fukada, So-ichiro; Yamamoto, Hiroshi; Yamanaka, Shinya; Nakahata, Tatsutoshi; Heike, Toshio

    2010-07-01

    Induced pluripotent stem (iPS) cells, which are a type of pluripotent stem cell generated from reprogrammed somatic cells, are expected to have potential for patient-oriented disease investigation, drug screening, toxicity tests, and transplantation therapies. Here, we demonstrated that murine iPS cells have the potential to develop in vitro into skeletal muscle stem/progenitor cells, which are almost equivalent to murine embryonic stem cells. Cells with strong in vitro myogenic potential effectively were enriched by fluorescence-activated cell sorting using the anti-satellite cell antibody SM/C-2.6. Furthermore, on transplantation into mdx mice, SM/C-2.6(+) cells exerted sustained myogenic lineage differentiation in injured muscles, while providing long-lived muscle stem cell support. Our data suggest that iPS cells have the potential to be used in clinical treatment of muscular dystrophies. PMID:20181939

  7. 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. PMID:25904840

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

    PubMed Central

    ALBEN?Z, I?IL; TÜRKER-?ENER, LEYLA; BA?, AYCAN; KALEL?O?LU, ?BRAHIM; NURTEN, RÜSTEM

    2012-01-01

    The aim of this study was to investigate changes in primitive hematopoietic cells through CD38 expression, identify the stage at which erythrocyte differentiation CD38 gains activity and the effects of serum factors on this expression by establishing a hematopoietic stem cell system in the erythroid development process. Using an immunomagnetic labeling and separation technique, CD34+ cells were selected from cord blood. The CD34+ cells were cultured in a 2 mM L-glutamine-enriched medium containing erythropoietin (Epo), penicillin-streptomycin and stem cell factor (SCF), and were incubated in 5% CO2 at 37°C. In erythroid development pathways following CD38 expression, primitive/progenitor human hematopoietic cells obtained from cord blood were assessed through the erythroid development process in a serum-free medium in the presence of proper SCF and Epo. At the end of the 26-day process, using staining with a Megacult-c staining kit, it was determined that progenitor cells nucleate and differentiate into erythroid cell lines of 8–10 ?m. During the course of this process, we analyzed increases over time in NAD glycohydrolase activity rates using the supernatant liquid samples. Results of co-culture experiments in cell culture studies showed that the stimulating effects of CD38 expression originate from specific serum factors. CD38 expression has been shown to occur at hematopoietic cell sources as well as at a number of differentiation levels. In the proliferation process the possible induction of CD38 through specific serum factors leads us to conclude that it may be involved in proliferation with a physiological task or that it may be involved in an event, such as an apoptotic process. PMID:22740856

  9. Human stem cells expressing novel TSP-1 variant have anti-angiogenic effect on brain tumors.

    PubMed

    van Eekelen, M; Sasportas, L S; Kasmieh, R; Yip, S; Figueiredo, J-L; Louis, D N; Weissleder, R; Shah, K

    2010-06-01

    Novel therapeutic agents combined with innovative modes of delivery and non-invasive imaging of drug delivery, pharmacokinetics and efficacy are crucial in developing effective clinical anticancer therapies. In this study, we have created and characterized multiple novel variants of anti-angiogenic protein thrombospondin (aaTSP-1) that comprises unique regions of three type-I-repeats of TSP-1 and used engineered human neural stem cells (hNSC) to provide sustained on-site delivery of secretable aaTSP-1 to tumor-vasculature. We show that hNSC-aaTSP-1 has anti-angiogenic effect on human brain and dermal microvascular endothelial cells co-cultured with established glioma cells and CD133+ glioma-initiating cells. Using human glioma cells and hNSC engineered with different combinations of fluorescent and bioluminescent marker proteins and employing multi-modality imaging techniques, we show that aaTSP-1 targets the vascular-component of gliomas and a single administration of hNSC-aaTSP-1 markedly reduces tumor vessel-density that results in inhibition of tumor-progression and increased survival in mice bearing highly malignant human gliomas. We also show that therapeutic hNSC do not proliferate and remain in an un-differentiated state in the brains of glioma-bearing mice. This study provides a platform for accelerated development of future cell-based therapies for cancer. PMID:20305695

  10. Human stem cells expressing novel TSP-1 variant have anti-angiogenic effect on brain tumors

    PubMed Central

    van Eekelen, Mark; Sasportas, Laura; Kasmieh, Randa; Yip, Stephen; Figueiredo, Jose-Luiz; Louis, David N.; Weissleder, Ralph; Shah, Khalid

    2012-01-01

    Novel therapeutic agents combined with innovative modes of delivery and non-invasive imaging of drug delivery, pharmacokinetics and efficacy are crucial in developing effective clinical anti-cancer therapies. In this study, we have created and characterized multiple novel variants of anti-angiogenic protein thrombospondin (aaTSP-1) that were comprised of unique regions of 3 type-I-repeats of TSP-1 and employed engineered human neural stem cells (hNSC) to provide sustained on-site delivery of secretable aaTSP-1 to tumor-vasculature. We show that hNSC-aaTSP-1 has anti-angiogenic effect on human brain and dermal microvascular endothelial cells co-cultured with established glioma cells and CD133+ glioma-initiating-cells. Using human glioma cells and hNSC engineered with different combinations of fluorescent and bioluminescent marker proteins and employing bioluminescence imaging and intravital-scanning microscopy, we show that aaTSP-1 targets the vascular-component of gliomas and a single administration of hNSC-aaTSP-1 markedly reduces tumor vessel-density that results in inhibition of tumor-progression and increased survival in mice bearing highly malignant human gliomas. We also show that therapeutic hNSC do not proliferate and remain in an un-differentiated state in the brains of glioma bearing mice. This study provides a platform for accelerated development of future cell based therapies for cancer. PMID:20305695

  11. Stem cells in the eye

    Microsoft Academic Search

    Mike Boulton; Julie Albon

    2004-01-01

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

  12. Adult Stem and Progenitor Cells

    Microsoft Academic Search

    Martine Geraerts; Catherine M. Verfaillie

    2009-01-01

    \\u000a The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out,\\u000a with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether\\u000a adult stem cells may have a greater plasticity than previously thought. Although cells with some features of

  13. Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing.

    PubMed

    Otsuka, Kensuke; Iwasaki, Toshiyasu

    2015-07-01

    An understanding of the dynamics of intestinal Lgr5(+) stem cells is important for elucidating the mechanism of colonic cancer development. We previously established a method for evaluating Lgr5(+) stem cells by tamoxifen-dependent Lgr5-lineage tracing and showed that high-dose-rate radiation stimulated replenishment of colonic stem cells. In this study, we evaluated the effects of low-dose-rate radiation on stem cell maintenance. Tamoxifen (4OHT)-injected Lgr5-EGFP-IRES-Cre(ERT2) × ROSA-LSL-LacZ mice were used, LacZ-labeled colonic crypts were enumerated, and the loss of LacZ(+) crypts under low-dose-rate radiation was estimated. After 4OHT treatment, the number of LacZ-labeled Lgr5(+) stem cells was higher in the colon of infant mice than in adult mice. The percentage of LacZ-labeled crypts in infant mice rapidly decreased after 4OHT treatment. However, the percentage of labeled crypts plateaued at ?2% at 4 weeks post-treatment and remained unchanged for up to 7 months. Thus, it will be advantageous to evaluate the long-term effects of low-dose-rate radiation. Next, we determined the percentages of LacZ-labeled crypts irradiated with 1 Gy administered at different dose rates. As reported in our previous study, mice exposed to high-dose-rate radiation (30 Gy/h) showed a marked replenishment (P = 0.04). However, mice exposed to low-dose-rate radiation (0.003 Gy/h) did not exhibit accelerated stem-cell replenishment (P = 0.47). These findings suggest the percentage of labeled crypts can serve as a useful indicator of the effects of dose rate on the stem cell pool. PMID:25832104

  14. Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing

    PubMed Central

    Otsuka, Kensuke; Iwasaki, Toshiyasu

    2015-01-01

    An understanding of the dynamics of intestinal Lgr5+ stem cells is important for elucidating the mechanism of colonic cancer development. We previously established a method for evaluating Lgr5+ stem cells by tamoxifen-dependent Lgr5-lineage tracing and showed that high-dose-rate radiation stimulated replenishment of colonic stem cells. In this study, we evaluated the effects of low-dose-rate radiation on stem cell maintenance. Tamoxifen (4OHT)-injected Lgr5-EGFP-IRES-CreERT2 × ROSA-LSL-LacZ mice were used, LacZ-labeled colonic crypts were enumerated, and the loss of LacZ+ crypts under low-dose-rate radiation was estimated. After 4OHT treatment, the number of LacZ-labeled Lgr5+ stem cells was higher in the colon of infant mice than in adult mice. The percentage of LacZ-labeled crypts in infant mice rapidly decreased after 4OHT treatment. However, the percentage of labeled crypts plateaued at ?2% at 4 weeks post-treatment and remained unchanged for up to 7 months. Thus, it will be advantageous to evaluate the long-term effects of low-dose-rate radiation. Next, we determined the percentages of LacZ-labeled crypts irradiated with 1 Gy administered at different dose rates. As reported in our previous study, mice exposed to high-dose-rate radiation (30 Gy/h) showed a marked replenishment (P = 0.04). However, mice exposed to low-dose-rate radiation (0.003 Gy/h) did not exhibit accelerated stem-cell replenishment (P = 0.47). These findings suggest the percentage of labeled crypts can serve as a useful indicator of the effects of dose rate on the stem cell pool. PMID:25832104

  15. The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells.

    PubMed

    Maurer, M; Echtenacher, B; Hültner, L; Kollias, G; Männel, D N; Langley, K E; Galli, S J

    1998-12-21

    Mast cells are thought to contribute significantly to the pathology and mortality associated with anaphylaxis and other allergic disorders. However, studies using genetically mast cell-deficient WBB6F1-KitW/KitW-v and congenic wild-type (WBB6F1-+/+) mice indicate that mast cells can also promote health, by participating in natural immune responses to bacterial infection. We previously reported that repetitive administration of the c-kit ligand, stem cell factor (SCF), can increase mast cell numbers in normal mice in vivo. In vitro studies have indicated that SCF can also modulate mast cell effector function. We now report that treatment with SCF can significantly improve the survival of normal C57BL/6 mice in a model of acute bacterial peritonitis, cecal ligation and puncture (CLP). Experiments in mast cell-reconstituted WBB6F1-KitW/KitW-v mice indicate that this effect of SCF treatment reflects, at least in part, the actions of SCF on mast cells. Repetitive administration of SCF also can enhance survival in mice that genetically lack tumor necrosis factor (TNF)-alpha, demonstrating that the ability of SCF treatment to improve survival after CLP does not solely reflect effects of SCF on mast cell- dependent (or -independent) production of TNF-alpha. These findings identify c-kit and mast cells as potential therapeutic targets for enhancing innate immune responses. PMID:9858520

  16. The c-kit Ligand, Stem Cell Factor, Can Enhance Innate Immunity Through Effects on Mast Cells

    PubMed Central

    Maurer, Marcus; Echtenacher, Bernd; Hültner, Lothar; Kollias, George; Männel, Daniela N.; Langley, Keith E.; Galli, Stephen J.

    1998-01-01

    Mast cells are thought to contribute significantly to the pathology and mortality associated with anaphylaxis and other allergic disorders. However, studies using genetically mast cell–deficient WBB6F1-KitW/KitW-v and congenic wild-type (WBB6F1-+/+) mice indicate that mast cells can also promote health, by participating in natural immune responses to bacterial infection. We previously reported that repetitive administration of the c-kit ligand, stem cell factor (SCF), can increase mast cell numbers in normal mice in vivo. In vitro studies have indicated that SCF can also modulate mast cell effector function. We now report that treatment with SCF can significantly improve the survival of normal C57BL/6 mice in a model of acute bacterial peritonitis, cecal ligation and puncture (CLP). Experiments in mast cell–reconstituted WBB6F1-KitW/KitW-v mice indicate that this effect of SCF treatment reflects, at least in part, the actions of SCF on mast cells. Repetitive administration of SCF also can enhance survival in mice that genetically lack tumor necrosis factor (TNF)-?, demonstrating that the ability of SCF treatment to improve survival after CLP does not solely reflect effects of SCF on mast cell– dependent (or –independent) production of TNF-?. These findings identify c-kit and mast cells as potential therapeutic targets for enhancing innate immune responses. PMID:9858520

  17. 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

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

    PubMed

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

    2015-03-01

    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. PMID:25652717

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

    PubMed

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

    2011-01-01

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

  20. Stem Cells and Asymmetric Cell Division

    Microsoft Academic Search

    Frank Hirth

    \\u000a Asymmetric stem cell division is a fundamental process used to generate cellular diversity and to provide a source of new\\u000a cells in developing and adult organisms. Asymmetric stem cell division leads to another stem cell via self-renewal, and a\\u000a second cell type which can be either a differentiating progenitor or a postmitotic cell. Experimental studies in model organisms\\u000a including the

  1. Pancreatic cancer stem cells

    PubMed Central

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

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

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

    PubMed

    Fliedner, T M; Tibken, B; Hofer, E P; Paul, W

    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 semi-autonomous 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 cell pool to 5-10% of normal is compatible with the assumption of its "reversible" damage (to be treated by conventional replacement therapy including cytokines), whereas the reduction of blood granulocytes to levels of less than 200-300 per mm3 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. In order to test the approach, the same model was used to correlate the changing granulocyte pattern seen after autologous blood stem cell transfusion in patients treated with a 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. PMID:8635902

  3. Effects of continuous passage on immunomodulatory properties of human adipose-derived stem cells.

    PubMed

    Wang, Xiyou; Liu, Cuilong; Li, Shaodan; Xu, Yong; Chen, Ping; Liu, Yi; Ding, Qiang; Wahapu, Wasilijiang; Hong, Baofa; Yang, Minghui

    2015-03-01

    Human adipose-derived stem cells (hADSCs) have the ability to influence immune response, and hence are key cell sources for tissue repair and regeneration. In this study we explored the effect of continuous passage on the immunomodulatory properties of hADSCs to provide some advises for large-scale production of hADSCs for clinical applications. We found that after continuous passage, the specific surface markers expression levels as well as the adipogenic and osteogenic differentiation capacities of hADSCs had no obvious changes. However, the secretion levels of IL-10 and HGF reduced dramatically along with passage numbers. Furthermore, the INF-? level was found higher in which medium peripheral blood mononuclear cells were co-cultured with hADSCs with higher passage numbers. Also, the in vivo experiments showed that the peritonitis model mice, which were injected with higher passage numbers of hADSCs, tended to have higher levels of inflammation. All these together indicated that continuous passage has only minor effect on the cell phenotypes but will impair the immunomodulatory properties of hADSCs. This suggests that hADSCs could be prepared by continuous passage, but only those cells of lower passage numbers would be ideal therapeutic tools. PMID:24777650

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

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

    2013-01-01

    The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal differentiation, they can be used to generate a model of endochondral ossification, but this limitation must be kept in mind when using them in cartilage tissue engineering application. PMID:23977373

  6. 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 ...

  7. Pregnancy and Stem Cell Behavior

    Microsoft Academic Search

    Kay-Uwe Wagner; Gilbert H. Smith

    2005-01-01

    The identification of cancer-initiating epithelial subtypes (i.e. cancer stem cells) is important for gaining a more comprehensive understanding of the process of neoplastic transformation and tumorigenesis. Since reproductive history has a major impact on breast tumorigenesis, it is reasonable to assume that pregnancy and lactation have enduring effects on the cancer susceptibility of multipotent progenitors. Using the Cre-lox technology as

  8. Cancer Stem Cells in Breast

    PubMed Central

    Charafe-Jauffret, Emmanuelle; Monville, Florence; Ginestier, Christophe; Dontu, Gabriela; Birnbaum, Daniel; Wicha, Max S.

    2009-01-01

    There is increasing evidence for the cancer stem cell hypothesis, which holds that cancers are driven by a cellular subcomponent that has stem cell properties, that is, self-renewal, tumorigenicity and multilineage differentiation capacity. The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the specific stem cell features, novel therapeutic pathways can be targeted. Following this approach, new molecules are currently in development. Focusing on the cross-talk between stem cells and their microenvironment is also a promising way to explore how to better target cancer stem cells and be curative. PMID:18544962

  9. Biological effects and mechanisms of action of mesenchymal stem cell therapy in chronic obstructive pulmonary disease.

    PubMed

    Jin, Zhixian; Pan, Xinghua; Zhou, Kaihua; Bi, Hong; Wang, Liyan; Yu, Lu; Wang, Qing

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality, worldwide. Given that the foremost risk factor leading to the development of COPD is cigarette smoke, the initial treatment for COPD is smoking cessation. Even after smoking cessation, inflammation, apoptosis and oxidative stress can persist and continue to contribute to COPD. Although current therapies for COPD (which are primarily based on anti-inflammatory drugs such as corticosteroids, theophylline and bronchodilators) reduce airway obstruction, limit COPD exacerbation and improve the patient's health-related quality-of-life, none can prevent disease progression or reduce mortality. Recent advances in stem cell research have provided novel insight into the potential of bone marrow mesenchymal stem cells (MSCs) in the treatment of several pulmonary diseases. This review article discusses the biological effects and mechanisms of action of MSC transplantation in COPD, and highlights the foundation that MSCs provide for novel therapeutic approaches in COPD. PMID:25834280

  10. 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.

  11. Effects of human yolk sac endothelial cells on supporting expansion of hematopoietic stem/progenitor cells from cord blood.

    PubMed

    Hu, Liangshan; Cheng, Lamei; Wang, Jian; Zhao, Huiping; Duan, Huaxin; Lu, Guangxiu

    2006-11-01

    In order to investigate the effects of human yolk sac-derived endothelial cells (hYSECs) on the expansion of human hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) in vitro, we purified hYSEC-like cells from 4-5 week human yolk sacs, which were morphologically similar to endothelial cells and expressed CD31, CD144 and vWF characteristics of endothelial cells. Then we isolated CD34(+) cells from UCB in culture under three different conditions: with hematopoietic cytokines (CKs), contact-coculture or noncontact-coculture with hYSECs supplemented with CKs, and found that the contact-coculture system had the strongest expansion efficiency in the total cells' (TCs) ability to form HPP-CFCs. Erythroid burst-forming units (BFU-E) increased 52.35-fold, 20.26-fold and 27.77-fold, respectively, compared with pre-expansion. We detected that the mRNA of Notch ligands such as Jagged1, Delta1 and Delta4 could express in hYSECs after contacted culture with UCB-CD34(+) cells but not the noncontacted cells by RT-PCR analysis. Therefore, we concluded that the contact-coculture system supplemented with CKs could support the expansion of UCB-HS/PCs in vitro, especially high potential proliferative colony-forming cells (HPP-CFC) and BFU-E, perhaps owing to Notch signal pathway. PMID:16962340

  12. Adult Stem Cells and Skeletal Muscle Regeneration.

    PubMed

    Costamagna, Domiziana; Berardi, Emanuele; Ceccarelli, Gabriele; Sampaolesi, Maurilio

    2015-01-01

    Satellite cells are unipotent stem cells involved in muscle regeneration. However, the skeletal muscle microenvironment exerts a dominant influence over stem cell function. The cell intrinsic complexity of the skeletal muscle niche located within the connective tissue between fibers includes motor neurons, tendons, blood vessels, immune response mediators and interstitial cells. All these cell types modulate the trafficking of stimuli responsible of muscle fiber regeneration. In addition, several stem cell types have been discovered in skeletal muscle tissue, mainly located in the interstitium. The majority of these stem cells appears to directly contribute to myogenic differentiation, although some of them are mainly implicated in paracrine effects. This review focuses on adult stem cells, which have been used for therapeutic purposes, mainly in animal models of chronic muscle degeneration. Emerging literature identifies other myogenic progenitors generated from pluripotent stem cells as potential candidates for the treatment of skeletal muscle degeneration. However, adult stem cells still represent the gold standard for future comparative studies. PMID:26122100

  13. Nanotopographical Control of Stem Cell Differentiation

    PubMed Central

    McNamara, Laura E.; McMurray, Rebecca J.; Biggs, Manus J. P.; Kantawong, Fahsai; Oreffo, Richard O. C.; Dalby, Matthew J.

    2010-01-01

    Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells. To address the mechanistic basis underlying the topographical effects on stem cells, the likely contributions of indirect (biochemical signal-mediated) and direct (force-mediated) mechanotransduction are discussed. Data from proteomic research is also outlined in relation to topography-mediated fate determination, as this approach provides insight into the global molecular changes at the level of the functional effectors. PMID:21350640

  14. 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 ...

  15. 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

  16. 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

  17. Additional effects of engineered stem cells expressing a therapeutic gene and interferon-? in a xenograft mouse model of endometrial cancer.

    PubMed

    Yi, Bo-Rim; Kim, Seung U; Choi, Kyung-Chul

    2015-07-01

    Endometrial cancer is the most common gynecologic malignancy in women worldwide. In the present study, we evaluated the effects of neural stem cell-directed enzyme/prodrug therapy (NDEPT) designed to more selectively target endometrial cancer. For this, we employed two different types of neural stem cells (NSCs), HB1.F3.CD and HB1.F3.CD.IFN-? cells. Cytosine deaminase (CD) can convert the non-toxic prodrug, 5-fluorocytosine (5-FC), into a toxic agent, 5-fluorouracil (5-FU), which inhibits DNA synthesis. IFN-? is a powerful cytotoxic cytokine that is released by activated immune cells or lymphocytes. In an animal model xenografted with endometrial Ishikawa cancer cells, the stem cells stained with CM-DiI were injected into nearby tumor masses and 5-FC was delivered by intraperitoneal injection. Co-expression of CD and IFN-? significantly inhibited the growth of cancer (~50-60%) in the presence of 5-FC. Among migration-induced factors, VEGF gene was highly expressed in endometrial cancer cells. Histological analysis showed that the aggressive nature of cancer was inhibited by 5-FC in the mice treated with the therapeutic stem cells. Furthermore, PCNA expression was more decreased in HB1.F3.CD.IFN-? treated mice rather than HB1.F3.CD treated mice. To confirm the in vitro combined effects of 5-FU and IFN-?, 5-FU was treated in Ishikawa cells. 5-FU increased the IFN-?/receptor 2 (IFNAR2) and BXA levels, indicating that 5-FU increased sensitivity of endometrial cancer cells to IFN-?, leading to apoptosis of cancer cells. Taken together, these results provide evidence for the efficacy of therapeutic stem cell-based immune therapy involving the targeted expression of CD and IFN-? genes at endometrial cancer sites. PMID:25963746

  18. Cell Stem Cell Endogenous Bone Marrow MSCs

    E-print Network

    Mootha, Vamsi K.

    ). The existence of multipotent bone marrow stromal cells (BMSCs), or skeletal/mesenchymal stem cells (SSCs.02.003 SUMMARY Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical bone- marrow-derived, Mx1+ stromal cells with ``MSC'' features. These cells respond to tissue stress

  19. Stem cell differentiation: Multipotency retained

    NASA Astrophysics Data System (ADS)

    Mrksich, Milan

    2011-08-01

    Stem cells that are cultured in the laboratory differentiate in response to the mechanical properties of the substrate and its topography. It is now shown that mesenchymal stem cell multipotency is prolonged when the cells are cultured on a surface patterned with an ordered arrangement of nanoscale pits.

  20. Stem cells from adipose tissue

    Microsoft Academic Search

    Malgorzata Witkowska-Zimny; Katarzyna Walenko

    2011-01-01

    This is a review of the growing scientific interest in the developmental plasticity and therapeutic potential of stromal cells\\u000a isolated from adipose tissue. Adipose-derived stem\\/stromal cells (ASCs) are multipotent somatic stem cells that are abundant\\u000a in fat tissue. It has been shown that ASCs can differentiate into several lineages, including adipose cells, chondrocytes,\\u000a osteoblasts, neuronal cells, endothelial cells, and cardiomyocytes.

  1. Human Embryonic Stem Cell Registry

    NSDL National Science Digital Library

    The National Institutes of Health (NIH) has recently released the Human Embryonic Stem Cell Registry in response to the President's announcement on August 9, 2001 to allow federal funds for stem cell research. The site lists the eleven laboratories or companies that meet the specific criteria for approved stem cell lines and explains the criteria themselves. The NIH gives the number of actual lines for each entity, the NIC and providers code for each, as well as contact information. The Website also provides links to those seeking additional information about NIH stem cell information, grants and funding opportunities, technology transfer issues, and further facts about the NIH.

  2. Generation of induced pluripotent stem cells from neural stem cells

    Microsoft Academic Search

    Jeong Beom Kim; Holm Zaehres; Marcos J Araúzo-Bravo; Hans R Schöler

    2009-01-01

    The generation of induced pluripotent stem (iPS) cells from mouse and human somatic cells by expression of defined transcription factors (Oct4, Sox2, c-Myc, Klf4, Nanog and Lin28) is a powerful tool for conducting basic research and investigating the potential of these cells for replacement therapies. In our laboratory, iPS cells have been generated from adult mouse neural stem cells (NSCs)

  3. 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

  4. 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

  5. Effects of Amyloid ?-Peptides and Gangliosides on Mouse Neural Stem Cells

    PubMed Central

    Itokazu, Yutaka; Kato-Negishi, Midori; Nakatani, Yoshihiko; Ariga, Toshio; Yu, Robert K.

    2015-01-01

    The interaction of amyloid ?-proteins (A?s) with membrane lipids has been postulated as an early event in A? fibril formation in Alzheimer’s disease. We evaluated the effects of several putative bioactive A?s and gangliosides on neural stem cells (NSCs) isolated from embryonic mouse brains or the subventricular zone of adult mouse brains. Incubation of the isolated NSCs with soluble A?1–40 alone did not cause any change in the number of NSCs, but soluble A?1–42 increased their number. Aggregated A?1–40 and A?1–42 increased the number of NSCs but soluble and aggregated A?25–35 decreased the number. Soluble A?1–40 and A?1–42 did not affect the number of apoptotic cells but aggregated A?1–40 and A?1–42 did. When NSCs were treated with a combination of GM1 or GD3 and soluble A?1–42, cell proliferation was enhanced, indicating that both GM1 and GD3 as well as A?s are involved in promoting cell proliferation and survival of NSCs. These observations suggest the potential of beneficial effects of using gangliosides and A?s for promoting NSC proliferation. PMID:23851714

  6. Effects of amyloid ?-peptides and gangliosides on mouse neural stem cells.

    PubMed

    Itokazu, Yutaka; Kato-Negishi, Midori; Nakatani, Yoshihiko; Ariga, Toshio; Yu, Robert K

    2013-10-01

    The interaction of amyloid ?-proteins (A?s) with membrane lipids has been postulated as an early event in A? fibril formation in Alzheimer's disease. We evaluated the effects of several putative bioactive A?s and gangliosides on neural stem cells (NSCs) isolated from embryonic mouse brains or the subventricular zone of adult mouse brains. Incubation of the isolated NSCs with soluble A?1-40 alone did not cause any change in the number of NSCs, but soluble A?1-42 increased their number. Aggregated A?1-40 and A?1-42 increased the number of NSCs but soluble and aggregated A?25-35 decreased the number. Soluble A?1-40 and A?1-42 did not affect the number of apoptotic cells but aggregated A?1-40 and A?1-42 did. When NSCs were treated with a combination of GM1 or GD3 and soluble A?1-42, cell proliferation was enhanced, indicating that both GM1 and GD3 as well as A?s are involved in promoting cell proliferation and survival of NSCs. These observations suggest the potential of beneficial effects of using gangliosides and A?s for promoting NSC proliferation. PMID:23851714

  7. Therapeutic effect of human clonal bone marrow-derived mesenchymal stem cells in severe acute pancreatitis.

    PubMed

    Jung, Kyung Hee; Yi, TacGhee; Son, Mi Kwon; Song, Sun U; Hong, Soon-Sun

    2015-05-01

    Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100 ?g/kg) and sequential LPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1 × 10(6)/head) were infused on 24 h after LPS injection via the tail vein. The rats were sacrificed 3 days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP. PMID:25142942

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

    PubMed Central

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

    2015-01-01

    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. 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

  10. Tracking Transplanted Bone Marrow Stem Cells and Their Effects in the Rat MCAO Stroke Model

    PubMed Central

    Goldmacher, Gregory V.; Nasser, Rena; Lee, Daniel Y.; Yigit, Sargon; Rosenwasser, Robert; Iacovitti, Lorraine

    2013-01-01

    In this study, rat bone marrow stromal stem cells (BMSCs) were tracked after IV administration to rats with experimental stroke caused by middle cerebral artery occlusion (MCAO). In addition, the effects of BMSC treatment on blood cell composition, brain glia and sensorimotor behavior was studied and compared to that which occurred spontaneously during the normal recovery process after stroke. We found that the vast majority of radiolabeled or fluorescently labeled BMSCs traveled to and remained in peripheral organs (lungs, spleen, liver) 3 days after IV injection in the MCAO rat. Once in the circulation, BMSCs also produced rapid alterations in host blood cell composition, increasing both neutrophil and total white blood cell count by 6 hours post-injection. In contrast, few injected BMSCs traveled to the brain and almost none endured there long term. Nonetheless, BMSC treatment produced dramatic changes in the number and activation of brain astroglia and microglia, particularly in the region of the infarct. These cellular changes were correlated with a marked improvement in performance on tests of sensory and motor function as compared to the partial recovery of function seen in PBS-injected control rats. We conclude that the notable recovery in function observed after systemic administration of BMSCs to MCAO rats is likely due to the cellular changes in blood and/or brain cell number, activation state and their cytokine/growth factor products. PMID:23555879

  11. Skeletal stem cells.

    PubMed

    Bianco, Paolo; Robey, Pamela G

    2015-03-15

    Skeletal stem cells (SSCs) reside in the postnatal bone marrow and give rise to cartilage, bone, hematopoiesis-supportive stroma and marrow adipocytes in defined in vivo assays. These lineages emerge in a specific sequence during embryonic development and post natal growth, and together comprise a continuous anatomical system, the bone-bone marrow organ. SSCs conjoin skeletal and hematopoietic physiology, and are a tool for understanding and ameliorating skeletal and hematopoietic disorders. Here and in the accompanying poster, we concisely discuss the biology of SSCs in the context of the development and postnatal physiology of skeletal lineages, to which their use in medicine must remain anchored. PMID:25758217

  12. 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

  13. 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

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

    PubMed Central

    2013-01-01

    Background The inflammatory response clinically observed after radiation has been described to correlate with elevated expression of cytokines and adhesion molecules by endothelial cells. Therapeutic compensation for this microvascular compromise could be an important approach in the treatment of irradiated wounds. Clinical reports describe the potential of adipose-derived stem cells to enhance wound healing, but the underlying cellular mechanisms remain largely unclear. Methods Human dermal microvascular endothelial cells (HDMEC) and human adipose-derived stem cells (ASC) were cultured in a co-culture setting and irradiated with sequential doses of 2 to 12 Gy. Cell count was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the supernatants using enzyme-linked immunosorbent assay (ELISA). Irradiated HDMEC and ASC as well as non-irradiated co-cultures, HDMEC or ASC respectively were used as controls. Results Cell count was significantly reduced in irradiated co-cultures of HDMEC and ASC compared to non-irradiated controls. Levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of the co-cultures were significantly less affected by external radiation in comparison to HDMEC. Conclusion The increased expression of cytokines and adhesion molecules by HDMEC after external radiation is mitigated in the co-culture setting with ASC. These in vitro changes seem to support the clinical observation that ASC may have a stabilizing effect when injected into irradiated wounds. PMID:23514369

  15. 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.

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

    Microsoft Academic Search

    Dan-yan Zhu; Yi-jia Lou

    2005-01-01

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

  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. Bone Tissue Engineering Using Human Mesenchymal Stem Cells: Effects of Scaffold Material and Medium Flow

    Microsoft Academic Search

    Lorenz Meinel; Vassilis Karageorgiou; Robert Fajardo; Brian Snyder; Vivek Shinde-Patil; Ludwig Zichner; David Kaplan; Robert Langer; Gordana Vunjak-Novakovic

    2004-01-01

    We report studies of bone tissue engineering using human mesenchymal stem cells (MSCs), a protein substrate (film or scaffold; fast degrading unmodified collagen, or slowly degrading cross-linked collagen and silk), and a bioreactor (static culture, spinner flask, or perfused cartridge). MSCs were isolated from human bone marrow, characterized for the expression of cell surface markers and the ability to undergo

  19. Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches

    PubMed Central

    Conboy, Irina M.; Rando, Thomas A.

    2012-01-01

    Aging is unmistakable and undeniable in mammals. Interestingly, mice develop cataracts, muscle atrophy, osteoporosis, obesity, diabetes and cognitive deficits after just 2–3 postnatal years, while it takes seven or more decades for the same age-specific phenotypes to develop in humans. Thus, chronological age corresponds differently with biological age in metazoan species and although many theories exist, we do not understand what controls the rate of mammalian aging. One interesting idea is that species-specific rate of aging represents a ratio of tissue attrition to tissue regeneration. Furthermore, current findings suggest that the age-imposed biochemical changes in the niches of tissue stem cells inhibit performance of this regenerative pool, which leads to the decline of tissue maintenance and repair. If true, slowing down stem cell and niche aging, thereby promoting tissue regeneration, could slow down the process of tissue and organismal aging. In this regard, recent studies of heterochronic parabiosis provide important clues as to the mechanisms of stem cell aging and suggest novel strategies for enhancing tissue repair in the old. Here we review current literature on the relationship between the vigor of tissue stem cells and the process of aging, with an emphasis on the rejuvenation of old tissues by the extrinsic modifications of stem cell niches. PMID:22617385

  20. Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches.

    PubMed

    Conboy, Irina M; Rando, Thomas A

    2012-06-15

    Aging is unmistakable and undeniable in mammals. Interestingly, mice develop cataracts, muscle atrophy, osteoporosis, obesity, diabetes and cognitive deficits after just 2-3 postnatal years, while it takes seven or more decades for the same age-specific phenotypes to develop in humans. Thus, chronological age corresponds differently with biological age in metazoan species and although many theories exist, we do not understand what controls the rate of mammalian aging. One interesting idea is that species-specific rate of aging represents a ratio of tissue attrition to tissue regeneration. Furthermore, current findings suggest that the age-imposed biochemical changes in the niches of tissue stem cells inhibit performance of this regenerative pool, which leads to the decline of tissue maintenance and repair. If true, slowing down stem cell and niche aging, thereby promoting tissue regeneration, could slow down the process of tissue and organismal aging. In this regard, recent studies of heterochronic parabiosis provide important clues as to the mechanisms of stem cell aging and suggest novel strategies for enhancing tissue repair in the old. Here we review current literature on the relationship between the vigor of tissue stem cells and the process of aging, with an emphasis on the rejuvenation of old tissues by the extrinsic modifications of stem cell niches. PMID:22617385

  1. 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

  2. Effects of Panax notoginseng saponins on proliferation and differentiation of rat hippocampal neural stem cells.

    PubMed

    Si, Yin-Chu; Zhang, Jian-Ping; Xie, Chun-E; Zhang, Li-Juan; Jiang, Xiang-Ning

    2011-01-01

    We aimed to investigate the effects of Panax notoginseng saponins (PNS) on proliferation, differentiation and self-renewal of rat hippocampal neural stem cells (NSCs) in vitro. Rat hippocampal NSCs were isolated from post-natal day 1 (P1) rats and cultured in a serum-free medium. The neurospheres were identified by the expressions of nestin, class III ?-tublin (Tuj-1) and glial fibrillary acid protein (GFAP). The cells were given PNS and subjected to oxygen glucose deprivation (OGD) as an in vitro model of brain ischemia reperfusion. The proliferation of NSCs was determined by MTT colorimetry, nestin/BrdU immunofluorescent double-labeling and RT-PCR. Differentiation of NSCs was assessed by immunofluorescent double-labeling of nestin/BrdU, nestin/vimentin, and nestin/Tuj-1. The primary cells and the first two passages of cells formed certain amount of neurospheres, the cells derived from a single cell clone also formed neurospheres. Nestin, BrdU, GFAP and Tuj-1-positive cells appeared in those neurospheres. Compared to the control group, PNS significantly promoted NSC proliferation and the expression of nestin/BrdU, and also enhanced Tuj-1, vimentin, and nestin mRNA expressions in hippocampal NSCs. PNS significantly increased area density, optical density and numbers of nestin/BrdU, nestin/vimentin, and nestin/Tuj-1 positive cells following OGD. These results indicate that PNS can promote proliferation and differentiation of hippocampus NCSs in vitro after OGD, suggesting its potential benefits on neurogenesis and neuroregeneration in brain ischemic injury. PMID:21905288

  3. 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

  4. EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Concise Review: Maturation Phases of Human Pluripotent Stem

    E-print Network

    George, Steven C.

    maturity? How well do hPS-CM model embryonic or adult CM in vitro? How does maturity change during in vitroEMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Concise Review: Maturation Phases of Human · In vitro cell culture · Maturity ABSTRACT Human pluripotent stem cell-derived cardiomyocytes (hPS-CM) may

  5. Differentiating Gametes from Stem Cells

    Microsoft Academic Search

    Ana Isabel Marqués-Marí; José Vicente Medrano; Carlos Simón

    \\u000a Embryonic stem cell lines derived from the inner cell mass of the blastocyst are pluripotent (they can differentiate into\\u000a all the different cell types) and have the ability to self-renewal in vitro, remaining undifferentiated. It has been demonstrated\\u000a that murine embryonic stem cells can give rise to structures very similar to sperm and oocytes in vitro. These differentiated cells are

  6. Metastasis and stem cell pathways

    Microsoft Academic Search

    Bryan C. Barnhart; M. Celeste Simon

    2007-01-01

    Recent studies have described a small population of self-renewing and multipotent cells within tumors termed “cancer stem\\u000a cells.” These cells share many traits with somatic and embryonic stem cells and are thought to be responsible for driving\\u000a tumor progression in a growing list of neoplastic diseases. Cells within solid tumors encounter hypoxia due to poor vascular\\u000a function. Both long-standing and

  7. 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.

  8. 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

  9. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease.

    PubMed

    Lamb, Rebecca; Ozsvari, Bela; Lisanti, Camilla L; Tanowitz, Herbert B; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2015-03-10

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent clinical trials with doxycycline and azithromycin (intended to target cancer-associated infections, but not cancer cells) have already shown positive therapeutic effects in cancer patients, although their ability to eradicate cancer stem cells was not yet appreciated. PMID:25625193

  10. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease

    PubMed Central

    Lisanti, Camilla L.; Tanowitz, Herbert B.; Howell, Anthony; Martinez-Outschoorn, Ubaldo E.; Sotgia, Federica; Lisanti, Michael P.

    2015-01-01

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of “stemness”, independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point – a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known “side-effect”, which could be harnessed instead as a “therapeutic effect”. Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent clinical trials with doxycycline and azithromycin (intended to target cancer-associated infections, but not cancer cells) have already shown positive therapeutic effects in cancer patients, although their ability to eradicate cancer stem cells was not yet appreciated. PMID:25625193

  11. 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

  12. How I treat late effects in adults after allogeneic stem cell transplantation

    PubMed Central

    Griffith, Michelle L.; Jagasia, Shubhada; Lee, Stephanie J.

    2011-01-01

    More than 25 000 allogeneic hematopoietic stem cell transplantations (allo-HCTs) are expected to be performed worldwide in 2010, a number that has been increasing yearly. With broadening indications, more options for allo-HCT, and improvement in survival, by 2020 there may be up to half a million long-term survivors after allo-HCT worldwide. These patients have increased risks for various late complications, which can cause morbidity and mortality. Most long-term survivors return to the care of their local hematologists/oncologists or primary care physicians, who may not be familiar with specialized monitoring recommendations for this patient population. The purpose of this article is to describe practical approaches to screening for and managing these late effects, with the goal of reducing preventable morbidity and mortality associated with allo-HCT. PMID:21193694

  13. 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

  14. 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

  15. Effect of co-transplantation of mesenchymal stem cells and hematopoietic stem cells as compared to hematopoietic stem cell transplantation alone in renal transplantation to achieve donor hypo-responsiveness

    Microsoft Academic Search

    Aruna V. VanikarHargovind; Hargovind L. Trivedi; A. Feroze; Kamal V. Kanodia; Shruti D. Dave; Pankaj R. Shah

    2011-01-01

    Introduction  We evaluated donor hypo-responsiveness in renal allograft recipients to donor adipose tissue-derived mesenchymal stem cell\\u000a (h-AD-MSC) +hematopoietic stem cell transplantation (HSCT) vs. HSCT alone.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Patients were divided into 2 demographically equal groups (n = 100) A and B subjected to equal non-myeloablative conditioning of target-specific irradiation, anti-T + B cell antibodies\\u000a and cyclophosphamide with HSCT. Group A was administered h-AD-MSC additionally. Transplantation was performed

  16. 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

  17. Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1

    PubMed Central

    Zarjou, Abolfazl; Kim, Junghyun; Traylor, Amie M.; Sanders, Paul W.; Balla, József; Agarwal, Anupam

    2011-01-01

    Multipotent mesenchymal stem cells (MSC) have become a popular and promising therapeutic approach in many clinical conditions. MSC are beneficial in animal models of acute kidney injury (AKI), by mediating differentiation-independent paracrine properties, and have prompted ongoing clinical trials to evaluate the safety and efficacy of MSC. Heme oxygenase-1 (HO-1) is induced in response to stress including AKI and has important anti-apoptotic, anti-inflammatory, and proangiogenic properties in these settings. We therefore examined whether HO-1 plays a role in the beneficial effects of MSC in AKI. We isolated MSC from bone marrow of age-matched HO-1+/+ and HO-1?/? mice. Our studies indicate that while differentiation of MSC into osteo- and adipocytic lineages did not differ between cells isolated from HO-1+/+ and HO-1?/? mice, MSC from HO-1?/? mice had significantly lower angiogenic potential. Moreover, HO-1?/? MSC demonstrated reduced expression and secretion of several important growth and proangiogenic factors (stromal cell-derived factor-1, vascular endothelial growth factor-A, and hepatocyte growth factor) compared with MSC derived from HO-1+/+ mice. In addition, conditioned medium of HO-1+/+ MSC rescued functional and morphological changes associated with cisplatin-induced AKI, while the HO-1?/?-conditioned medium was ineffectual. Our studies indicate that HO-1 plays an important role in MSC-mediated protection. The results expand understanding of the renoprotective effects of MSC and may provide novel strategies to better utilize MSC in various disease models. PMID:21048024

  18. Nonmalignant late effects in survivors of partially matched donor hematopoietic stem cell transplantation.

    PubMed

    Mo, Xiao-Dong; Xu, Lan-Ping; Liu, Dai-Hong; Zhang, Xiao-Hui; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Yu; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2013-05-01

    Human leukocyte antigen (HLA) partially matched related donor (PMRD) hematopoietic stem cell transplantation (HSCT) is an effective option for hematological malignancies. In this study, the nonmalignant late effects of PMRD HSCT were evaluated and compared with HLA-identical sibling donor (ISD) HSCT. Three hundred thirteen patients (ISD, n = 160; PMRD, n = 153) who survived at least 6 months and received regular follow-up examinations after their HSCT were enrolled. The 5-year cumulative incidence (±SE) of at least one late effect and multiple late effects was 47.30% ± .17% versus 58.21% ± .16% (P = .134) and 17.97% ± .10% versus 34.28% ± .15% (P = .001) for PMRD HSCT recipients versus ISD HSCT recipients, respectively. The cumulative incidence of keratoconjunctivitis sicca, periodontitis, ankylosis, myalgia, and nephrotic syndrome was lower among PMRD HSCT recipients compared with ISD HSCT recipients. Severe chronic graft-versus-host disease, multiple pre-HSCT chemotherapy cycles, female donor, and older age were risk factors for at least one late effect. Female donor, older age, and long-term immunosuppressive therapy were associated with multiple late effects. In summary, PMRD HSCT recipients have a lower risk of late effects compared with ISD HSCT recipients, possibly due to differences in protocols for graft-versus-host disease prophylaxis, and long-term follow-up after transplantation is recommended. PMID:23396212

  19. 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

  20. 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

  1. Plasticity of Adult Stem Cells

    Microsoft Academic Search

    Amy J Wagers; Irving L Weissman

    2004-01-01

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

  2. 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

  3. Gastrointestinal stem cell up-to-date

    PubMed Central

    Pirvulet, V

    2015-01-01

    Cellular and tissue regeneration in the gastrointestinal tract depends on stem cells with properties of self-renewal, clonogenicity, and multipotency. Progress in stem cell research and the identification of potential gastric, intestinal, colonic stem cells new markers and the signaling pathways provide hope for the use of stem cells in regenerative medicine and treatments for disease. This review provides an overview of the different types of stem cells, focusing on tissue-restricted adult stem cells. PMID:25866586

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

    PubMed

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

    2008-01-01

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

  5. Use of Combinatorial Screening to Discover Protocols That Effectively Direct the Differentiation of Stem Cells

    Microsoft Academic Search

    Yen Choo

    Embryonic stem cells (ESCs) have the rare ability to differentiate into all cell types that comprise the human adult, offering\\u000a an unprecedented opportunity to perform developmental studies in vitro and promising unlimited supplies of somatic cells for numerous biomedical applications including transplantation medicine.\\u000a Reliably controlling the differentiation of ESCs in vitro by conventional methods requires an understanding of complex developmental

  6. 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.

  7. Stem cell mechanics: Auxetic nuclei

    NASA Astrophysics Data System (ADS)

    Wang, Ning

    2014-06-01

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

  8. Engineering stem cells for therapy.

    PubMed

    Mendez-Pertuz, Marinela; Hughes, Chris; Annenkov, Alex; Daly, Gordon; Chernajovsky, Yuti

    2006-07-01

    The differentiation of a stem cell is dependent on the environmental cues that it receives and can be modulated by the expression of different master regulators or by secreted factors or inducers. The use of genetically modified stem cells to express the required factors can direct differentiation along the requisite pathway. This approach to the engineering of stem cells is important, as control of the pluripotentiality of stem cells is necessary in order to avoid unwanted growth, migration or differentiation to nontarget tissues. The authors provide an overview of the stem cell engineering field, highlighting challenges and solutions, and focusing on recent developments in therapeutic applications in areas such as autoimmunity, CNS lesions, bone and joint diseases, cancer and myocardial infarction. PMID:17465851

  9. 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

  10. Effects and neuro-toxic mechanisms of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl and endosulfan in neuronal stem cells.

    PubMed

    Kang, K S; Park, J E; Ryu, D Y; Lee, Y S

    2001-11-01

    Endocrine disrupters are exogenous compounds thought to mimic the action of estrogen or other hormones and influence endocrine activity in the body (Juberg, 2000). These chemicals have adverse effects not only in the reproductive system but also in the central nervous system during development and throughout life. Polychlorinated biphenyls (PCBs) are a class of environmentally persistent and widespread halogenated hydrocarbons. It has been reported that PCBs are potential neurotoxicants. Endosulfan is an organochlorine insecticide that is extensively used to control pests in vegetables, cotton, and fruits. To determine the effect of 2, 2', 4, 4', 5, 5',-hexachlorobiphenyl(2, 4, 5-HCB) and endosulfan on embryo nervous system, we isolated neural stem cells from rat brain at embryonic day 17. Isolated neural stem cells showed pluripotenty. Stem cells could differentiate into neurons and glia. Neurite formation in endosulfan and 2, 4, 5-HCB treated cells. And it appeared to be decreased as compared with that in untreated cells. In order to know the neuro-toxic mechanisms of 2, 4, 5-HCB and endosulfan in neuronal stem cells, we investigated mitogen-activated protein kinase activity (MAPK) and gap junctional intercellular communication (GJIC). Endosulfan decreased the MAPK activity in dose dependent manner. Endosulfan and 2, 4, 5-HCB inhibited GJIC compared to the untreated cell by scrape loading dye transfer (SL/DT). 2, 4, 5-HCB and endosulfan decreased the expression of connexin 43 in dose dependent manner. These results indicated that 2, 4, 5-HCB and endosulfan may inhibit differentiation and proliferation of neural stem cells and gap junctional intercellular communication which play a crucial role in the maintenance of cellular homeostasis. PMID:11767051

  11. 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.

  12. 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

  13. A Preliminary Study of the Effects of Liposuction Technique on Adipose-derived Stem Cell Viability and Abundance

    Microsoft Academic Search

    Daniel P Murphy

    2012-01-01

    The potential of stem cells to replace damaged or malfunctioning tissues has been studied for some time. Recent studies using adipose-derived mesenchymal stem cells (ADSCs) have shown promise for adult stem cells as a rich, clinically relevant population. Our lab has previously determined that the quantity and quality of ADSCs varies depending on patient age and sex, anatomical location of

  14. 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

  15. Effects of Tithonia diversifolia (Hemsl.) A. Gray extract on adipocyte differentiation of human mesenchymal stem cells.

    PubMed

    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

  16. 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

  17. Emerging models and paradigms for stem cell ageing

    Microsoft Academic Search

    D. Leanne Jones; Thomas A. Rando

    2011-01-01

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

  18. Adult Stem Cells and Diseases of Aging.

    PubMed

    Boyette, Lisa B; Tuan, Rocky S

    2014-01-21

    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

  19. 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.

  20. 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.

  1. [Protective effect of bone marrow mesenchymal stem cell-derived microvesicles on glutamate injured PC12 cells].

    PubMed

    Lin, Shan-Shan; Zhu, Bo; Guo, Zi-Kuan; Huang, Guo-Zhi

    2014-08-01

    This study was aimed to investigate the protective effect of bone mesenchymal stem cell-derived microvesicles (BMMSC-MV) on glutamate injured PC12 cells so as to elucidate the mechanism of the neural damage repair. BMMSC were isolated and purified with density-gradient centrifugation method, BMMSC-MV were harvested from the supernatants of BMMSC by hypothermal ultracentrifugation method. The surface markers of BMMSC reacted against different antibodies were detected by flow cytometry. The morphology features of MV were observed under an electron microscope. Experiment was divided into three groups, one was a control group, and the other two were glutamate-injured group and co-culture group of BMMSC-MV and glutamate-damaged cells respectively. MTT test was used to evaluate the proliferative status of PC12 cells and the AnnexinV-FITC detecting kit and Hoechst33342 were used to detect the apoptosis of PC12 cells in different groups. The results showed that BMMSC isolated from rat bone marrow were highly positive for CD29, CD44 and negative for CD31, CD34 and CD45. The morphology of MV was round and the vesicles were homogenous in size. BMMSC-MV exhibited a protective effect on the excitotoxicity-injured PC12 cells, displaying increase of cell viability, decrease of Annexin-V/PI staining positive and nuclear condensed cells. It is concluded that BMMSC-MV can protect PC12 cells from glutamate-induced apoptosis, suggesting that BMMSC-MV may be a potential candidate for treatment of neurological diseases.This study provides the preliminary experimental and theoretical evidence for use of BMMSC-MV in treatment of neural excited damage. PMID:25130832

  2. Advances in Stem Cell Mobilization

    PubMed Central

    Hopman, Rusudan K.; DiPersio, John F.

    2014-01-01

    Use of granulocyte colony stimulating factor (G-CSF)–mobilized peripheral blood hematopoietic progenitor cells (HPC) has largely replaced bone marrow (BM) as a source of stem cells for both autologous and allogeneic cell transplantation. With G-CSF alone, up to 35% of patients are unable to mobilize sufficient numbers of CD34 cells/kg to ensure successful and consistent multi-lineage engraftment and sustained hematopoietic recovery. To this end, research is ongoing to identify new agents or combinations which will lead to the most effective and efficient stem cell mobilization strategies, especially in those patients who are at risk for mobilization failure. We describe both established agents and novel strategies at various stages of development. The latter include but are not limited to drugs that target the SDF-1/CXCR4 axis, S1P agonists, VCAM/VLA-4 inhibitors, parathyroid hormone, proteosome inhibitors, Gro?, and agents that stabilize HIF. While none of the novel agents have yet gained an established role in HPC mobilization in clinical practice, many early studies exploring these new pathways show promising results and warrant further investigation. PMID:24476957

  3. Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair

    PubMed Central

    Lee, Shin-Jeong; Park, Changwon; Lee, Ji Yoon; Kim, Sangsung; Kwon, Pil Jae; Kim, Woansang; Jeon, Yong Heui; Lee, Eugine; Yoon, Young-sup

    2015-01-01

    Human pluripotent stem cells (hPSCs) have emerged as an important source for cell therapy. However, to date, no studies demonstrated generation of purified hPSC-derived lymphatic endothelial cells (LECs) and tested their therapeutic potential in disease models. Here we sought to differentiate hPSCs into the LEC lineage, purify them with LEC markers, and evaluate their therapeutic effects. We found that an OP9-assisted culture system reinforced by addition of VEGF-A, VEGF-C, and EGF most efficiently generated LECs, which were then isolated via FACS-sorting with LYVE-1 and PODOPLANIN. These hPSC-derived LYVE-1+PODOPLANIN+cells showed a pure committed LEC phenotype, formed new lymphatic vessels, and expressed lymphangiogenic factors at high levels. These hPSC-derived LECs enhanced wound healing through lymphangiogenesis and lymphvasculogenesis. Here we report, for the first time, that LECs can be selectively isolated from differentiating hPSCs, and that these cells are potent for lymphatic vessel formation in vivo and wound healing. This system and the purified hPSC-derived LECs can serve as a new platform for studying LEC development as well as for cell therapy. PMID:26066093

  4. The Effects of Naproxen on Chondrogenesis of Human Mesenchymal Stem Cells.

    PubMed

    Antoniou, John; Wang, Hong Tian; Hadjab, Insaf; Aldebeyan, Sultan; Alaqeel, Motaz A; Meij, Björn P; Tryfonidou, Marianna A; Mwale, Fackson

    2015-07-01

    Currently, there are no established treatments to prevent, stop, or even retard the degeneration of articular cartilage in osteoarthritis (OA). Biological repair of the degenerating articular cartilage would be preferable to surgery. There is no benign site where autologous chondrocytes can be harvested and used as a cell source for cartilage repair, leaving mesenchymal stem cells (MSCs) as an attractive option. However, MSCs from OA patients have been shown to constitutively express collagen type X (COL-X), a marker of late-stage chondrocyte hypertrophy. We recently found that naproxen (Npx), but not other nonsteroidal anti-inflammatory drugs, can induce collagen type X alpha 1 (COL10A1) gene expression in bone marrow-derived MSCs from healthy and OA donors. In this study, we determined the effect of Npx on COL10A1 expression and investigated the intracellular signaling pathways that mediate such effect in normal human MSCs during chondrogenesis. MSCs were cultured in standard chondrogenic differentiation media supplemented with or without Npx. Our results show that Npx can regulate chondrogenic differentiation by affecting the gene expression of both Indian hedgehog and parathyroid hormone/parathyroid hormone-related protein signaling pathways in a time-dependent manner, suggesting a complex interaction of different signaling pathways during the process. PMID:25873236

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

    PubMed Central

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

    2012-01-01

    Mesenchymal stem cells (MSC) are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential in medulloblastomas (MB) has not been explored to date. In this study, we engineered human MSC to express a potent and secretable variant of a tumor specific agent, tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL) and assessed the ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and -resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance correlates with the expression of its cognate death receptor (DR)5 and MSC-S-TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines. In TRAIL-resistant MB, we show upregulation of DR4/5 levels when pre-treated with MS-275 and a subsequent sensitization to MSC-S-TRAIL mediated apoptosis. Using intracranially implanted MB and MSC lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that MSC-S-TRAIL has significant anti-tumor effects in mice bearing TRAIL-sensitive and MS-275 pre-treated TRAIL-resistant MBs. To our knowledge, this is the first study that explores the use of human MSC as MB-targeting therapeutic-vehicles in vivo in TRAIL-sensitive and resistant tumors, and has implications for developing effective therapies for patients with medulloblastomas. PMID:23145127

  6. Evaluating the effect of therapeutic stem cells on TRAIL resistant and sensitive medulloblastomas.

    PubMed

    Nesterenko, Irina; Wanningen, Simone; Bagci-Onder, Tugba; Anderegg, Maarten; Shah, Khalid

    2012-01-01

    Mesenchymal stem cells (MSC) are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential in medulloblastomas (MB) has not been explored to date. In this study, we engineered human MSC to express a potent and secretable variant of a tumor specific agent, tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL) and assessed the ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and -resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance correlates with the expression of its cognate death receptor (DR)5 and MSC-S-TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines. In TRAIL-resistant MB, we show upregulation of DR4/5 levels when pre-treated with MS-275 and a subsequent sensitization to MSC-S-TRAIL mediated apoptosis. Using intracranially implanted MB and MSC lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that MSC-S-TRAIL has significant anti-tumor effects in mice bearing TRAIL-sensitive and MS-275 pre-treated TRAIL-resistant MBs. To our knowledge, this is the first study that explores the use of human MSC as MB-targeting therapeutic-vehicles in vivo in TRAIL-sensitive and resistant tumors, and has implications for developing effective therapies for patients with medulloblastomas. PMID:23145127

  7. Cell Stem Cell Dietary and Metabolic Control

    E-print Network

    Sabatini, David M.

    Cell Stem Cell Review Dietary and Metabolic Control of Stem Cell Function in Physiology and Cancer in rodents have been audited by using two extremes of nutrient availability: calorie restriction and dietary or genetic models of obesity. Calorie restriction (also referred to as dietary restriction) in many animal

  8. Endometrial stem/progenitor cells.

    PubMed

    Maruyama, Tetsuo

    2014-09-01

    Human endometrium regenerates and regresses with each menstrual cycle under hormonal control throughout a woman's reproductive life. The cyclical regeneration and remodeling potentials allude to the existence of stem/progenitor cells in the endometrium. There is increasing evidence that human endometrium contains small numbers of stem-like cells capable of self-renewal, multiple differentiation and tissue reconstitution. Although the precise identity of endometrial stem/progenitor cells remains elusive, these cells are thought to play pivotal role(s) in the physiological remodeling and regeneration of the human endometrium and also in the pathogenesis of endometrium-associated diseases, such as endometriosis. PMID:25160689

  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. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation.

    PubMed

    Zhou, Xiaoou; Dotti, Gianpietro; Krance, Robert A; Martinez, Caridad A; Naik, Swati; Kamble, Rammurti T; Durett, April G; Dakhova, Olga; Savoldo, Barbara; Di Stasi, Antonio; Spencer, David M; Lin, Yu-Feng; Liu, Hao; Grilley, Bambi J; Gee, Adrian P; Rooney, Cliona M; Heslop, Helen E; Brenner, Malcolm K

    2015-06-25

    To test the feasibility of a single T-cell manipulation to eliminate alloreactivity while sparing antiviral and antitumor T cells, we infused 12 haploidentical hematopoietic stem cell transplant patients with increasing numbers of alloreplete haploidentical T cells expressing the inducible caspase 9 suicide gene (iC9-T cells). We determined whether the iC9-T cells produced immune reconstitution and if any resultant graft-versus-host disease (GVHD) could be controlled by administration of a chemical inducer of dimerization (CID; AP1903/Rimiducid). All patients receiving >10(4) alloreplete iC9-T lymphocytes per kilogram achieved rapid reconstitution of immune responses toward 5 major pathogenic viruses and concomitant control of active infections. Four patients received a single AP1903 dose. CID infusion eliminated 85% to 95% of circulating CD3(+)CD19(+) T cells within 30 minutes, with no recurrence of GVHD within 90 days. In one patient, symptoms and signs of GVHD-associated cytokine release syndrome (CRS-hyperpyrexia, high levels of proinflammatory cytokines, and rash) resolved within 2 hours of AP1903 infusion. One patient with varicella zoster virus meningitis and acute GVHD had iC9-T cells present in the cerebrospinal fluid, which were reduced by >90% after CID. Notably, virus-specific T cells recovered even after AP1903 administration and continued to protect against infection. Hence, alloreplete iC9-T cells can reconstitute immunity posttransplant and administration of CID can eliminate them from both peripheral blood and the central nervous system (CNS), leading to rapid resolution of GVHD and CRS. The approach may therefore be useful for the rapid and effective treatment of toxicities associated with infusion of engineered T lymphocytes. This trial was registered at www.clinicaltrials.gov as #NCT01494103. PMID:25977584

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

    Microsoft Academic Search

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

    2008-01-01

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

  12. Polyester ?-assay chip for stem cell studies

    PubMed Central

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

    2012-01-01

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

  13. 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

  14. Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects

    Microsoft Academic Search

    Jay G. Shake; Peter J. Gruber; William A. Baumgartner; Guylaine Senechal; Jennifer Meyers; J. Mark Redmond; Mark F. Pittenger; Bradley J. Martin

    2002-01-01

    Background. A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model.Methods. MSCs were isolated and expanded from bone marrow aspirates of 14

  15. The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model

    Microsoft Academic Search

    Sang Yup Lim; Yong Sook Kim; Youngkeun Ahn; Myung Ho Jeong; Moon Hwa Hong; Soo Yeon Joo; Kwang Il Nam; Jeong Gwan Cho; Peter M. Kang; Jong Chun Park

    Objective: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart. Methods: MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection (Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs). Myocardial single

  16. 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

  17. The multifaceted adult epidermal stem cell

    Microsoft Academic Search

    Laure Gambardella; Yann Barrandon

    2003-01-01

    Adult epidermal stem cells renew the epithelial compartment of the skin throughout life and are the most accessible of all adult stem cells. Most importantly, epidermal stem cells can be efficiently cultivated and transplanted, a significant advantage for cell and gene therapy. Recent work has pointed to the hair follicle as the main repository of multipotent stem cells in skin.

  18. 28. Embryonic and adult stem cell therapy

    Microsoft Academic Search

    Carl T. Henningson; Marisha A. Stanislaus; Alan M. Gewirtz

    2003-01-01

    Stem cells are characterized by the ability to remain undifferentiated and to self-renew. Embryonic stem cells derived from blastocysts are pluripotent (able to differentiate into many cell types). Adult stem cells, which were traditionally thought to be monopotent multipotent, or tissue restricted, have recently also been shown to have pluripotent properties. Adult bone marrow stem cells have been shown to

  19. 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

  20. The effect of controlled growth factor delivery on embryonic stem cell differentiation inside fibrin scaffolds

    Microsoft Academic Search

    Stephanie M. Willerth; Allison Rader; Shelly E. Sakiyama-Elbert

    2008-01-01

    The goal of this project was to develop 3-D biomaterial scaffolds that present cues to direct the differentiation of embryonic stem (ES) cell-derived neural progenitor cells, seeded inside the scaffolds, into mature neural phenotypes, specifically neurons and oligodendrocytes. Release studies were performed to determine the appropriate conditions for retention of neurotrophin-3 (NT-3), sonic hedgehog, and platelet-derived growth factor (PDGF) by

  1. Effective vitrification of human induced pluripotent stem cells using carboxylated ?-poly- l-lysine

    Microsoft Academic Search

    Kazuaki Matsumura; Jung Yoon Bae; Hak Hee Kim; Suong Hyu Hyon

    2011-01-01

    Derivation of human induced pluripotent stem (iPS) cells could enable their widespread application in future. Establishment of highly efficient and reliable methods for their preservation is a prerequisite for these applications. In this study, we developed a vitrification solution comprising ethylene glycol (EG) and sucrose as well as carboxylated ?-poly-l-lysine (PLL); this solution inhibited devitrification. Human iPS cells were vitrified

  2. 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

  3. Stem Cells in the Lung

    PubMed Central

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

    2007-01-01

    The lung is composed of two major anatomically distinct regions—the conducting airways and gas-exchanging airspaces. From a cell biology standpoint, the conducting airways can be further divided into two major compartments, the tracheobronchial and bronchiolar airways, while the alveolar regions of the lung make up the gas-exchanging airspaces. Each of these regions consists of distinct epithelial cell types with unique cellular physiologies and stem cell compartments. This chapter focuses on model systems with which to study stem cells in the adult tracheobronchial airways, also referred to as the proximal airway of the lung. Important in such models is an appreciation for the diversity of stem cell niches in the conducting airways that provide localized environmental signals to both maintain and mobilize stem cells in the setting of airway injury and normal cellular turnover. Because cellular turnover in airways is relatively slow, methods for analysis of stem cells in vivo have required prior injury to the lung. In contrast, ex vivo and in vitro models for analysis of airway stem cells have used genetic markers to track lineage relationships together with reconstitution systems that mimic airway biology. Over the past decades, several widely acceptable methods have been developed and used in the characterization of adult airway stem/ progenitor cells. These include localization of label-retaining cells (LRCs), retroviral tagging of epithelial cells seeded into xenografts, air–liquid interface cultures to track clonal proliferative potential, and multiple transgenic mouse models. This chapter reviews the biologic context and use of these models while providing detailed methods for several of the more broadly useful models for studying adult airway stem/progenitor cell types. PMID:17141060

  4. Combinational effect of matrix elasticity and alendronate density on differentiation of rat mesenchymal stem cells.

    PubMed

    Jiang, Pengfei; Mao, Zhengwei; Gao, Changyou

    2015-06-01

    Differentiation of mesenchymal stem cells (MSCs) is regulated by multivariate physical and chemical signals in a complicated microenvironment. In this study, polymerizable double bonds (GelMA) and osteo-inductive alendronate (Aln) (Aln-GelMA) were sequentially grafted onto gelatin molecules. The biocompatible hydrogels with defined stiffness in the range of 4-40 kPa were prepared by using polyethylene glycol diacrylate (PEGDA) as additional crosslinker. The Aln density was adjusted from 0 to 4 ?M by controlling the ratio between the GelMA and Aln-GelMA. The combinational effects of stiffness and Aln density on osteogenic differentiation of MSCs were then studied in terms of ALP activity, collagen type I and osteocalcin expression, and calcium deposition. The results indicated that the stiffness and Aln density could synergistically improve the expression of all these osteogenesis markers. Their osteo-inductive effects are comparable to some extent, and high Aln density could be more effective than the stiffness. PMID:25805109

  5. 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, Kaohsiung Medical University, Kaohsiung, Taiwan *Correspondence: sallytemple@nynsci.org DOI 10.1016/j.stem

  6. 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.

  7. Enamel Matrix Derivative has No Effect on the Chondrogenic Differentiation of Mesenchymal Stem Cells

    PubMed Central

    Groeneveldt, Lisanne C.; Knuth, Callie; Witte-Bouma, Janneke; O’Brien, Fergal J.; Wolvius, Eppo B.; Farrell, Eric

    2014-01-01

    Background: Treatment of large bone defects due to trauma, tumor resection, or congenital abnormalities is challenging. Bone tissue engineering using mesenchymal stem cells (MSCs) represents a promising treatment option. However, the quantity and quality of engineered bone tissue are not sufficient to fill large bone defects. The aim of this study was to determine if the addition of enamel matrix derivative (EMD) improves in vitro chondrogenic priming of MSCs to ultimately improve in vivo MSC mediated endochondral bone formation. Methods: MSCs were chondrogenically differentiated in 2.0?×?105 cell pellets in medium supplemented with TGF?3 in the absence or presence of 1, 10, or 100??g/mL EMD. Samples were analyzed for gene expression of RUNX2, Col II, Col X, and Sox9. Protein and glycoaminoglycan (GAG) production were also investigated via DMB assays, histology, and immunohistochemistry. Osteogenic and adipogenic differentiation capacity were also assessed. Results: The addition of EMD did not negatively affect chondrogenic differentiation of adult human MSCs. EMD did not appear to alter GAG production or expression of chondrogenic genes. Osteogenic and adipogenic differentiation were also unaffected though a trend toward decreased adipogenic gene expression was observed. Conclusion: EMD does not affect chondrogenic differentiation of adult human MSCs. As such the use of EMD in combination with chondrogenically primed MSCs for periodontal bone tissue repair is unlikely to have negative effects on MSC differentiation. PMID:25229057

  8. Neurorestorative Effect of Urinary Bladder Matrix-mediated Neural Stem Cell Transplantation Following Traumatic Brain Injury in Rats

    PubMed Central

    Ren, ZH; Zhang, L; Brown, BN; Cui, XT; Badylak, SF; Cai, YN; Guan, YQ; Leak, Rehana K.; Chen, J; Ji, X; Chen, L

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of cell death and disability among young adults and lacks a successful therapeutic strategy. The multiphasic injuries of TBI severely limit the success of conventional pharmacological approaches. Recent successes with transplantation of stem cells in bioactive scaffolds in other injury paradigms provide new hope for the treatment of TBI. In this study, we transplanted neural stem cells (0.5×105 cells/?l) cultured in a bioactive scaffold derived from porcine urinary bladder matrix (UBM; 4 injection sites, 2.5?l each) into the rat brain following controlled cortical impact (CCI, velocity, 4.0 m/sec; duration, 0.5 sec; depth, 3.2mm). We evaluated the effectiveness of this strategy to combat the loss of motor, memory and cognitive faculties. Before transplantation, compatibility experiments showed that UBM was able to support extended proliferation and differentiation of neural stem cells. Together with its reported anti-inflammatory properties and rapid degradation characteristics in vivo, UBM emerged to be an ideal scaffold. The transplants reduced neuron/tissue loss and white matter injury, and also significantly ameliorated motor, memory, and cognitive impairments. Furthermore, exposure to UBM alone was sufficient to decrease the loss of sensorimotor skills from TBI (examined 3–28 days post-CCI). However, only UBMs that contained proliferating neural stem cells helped attenuate memory and cognitive impairments (examined 26–28 days post-CCI). In summary, these results demonstrate the therapeutic efficacy of stem cells in bioactive scaffolds against TBI and show promise for translation into future clinical use. PMID:23469853

  9. Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells

    Microsoft Academic Search

    Carla F. Kim

    2007-01-01

    New discoveries in stem cell biology are making the biology of solid tissues increasingly complex. Important seminal studies demonstrating the presence of damage-resistant cell populations together with new isolation and characterization techniques suggest that stem cells exist in the adult lung. More detailed in vivo molecular and cellular characterization of bronchioalveolar stem cells (BASCs), other putative lung stem and progenitor

  10. Progress in myeloma stem cells

    PubMed Central

    Cruz, Richard Dela; Tricot, Guido; Zangari, Maurizio; Zhan, Fenghuang

    2011-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy in the United States and affects about 4 in 100,000 Americans. Even though much progress has been made in MM therapy, MM remains an incurable disease for the vast majority of patients. The existence of MM stem cell is considered one of the major causes of MM drug-resistance, leading to relapse. This highlights the importance and urgency of developing approaches to target MM stem cells. However, very little is known about the molecular characteristics of the MM stem cells, which makes it difficult to target MM stem cells therapeutically. Evidence of the existence of a myeloma stem cell has been provided by Matsui et al. showing that the CD138- and CD20+ fraction, which is a minor population of the MM cells, has a greater clonogenic potential and has the phenotype of a memory B-cell (CD19+, CD27+). In this review, we report recent progress of cell surface markers in cancer stem cells, especially in myeloma and the molecular mechanisms related to drug resistance and myeloma disease progression. PMID:22432075

  11. Progress in myeloma stem cells.

    PubMed

    Cruz, Richard Dela; Tricot, Guido; Zangari, Maurizio; Zhan, Fenghuang

    2011-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy in the United States and affects about 4 in 100,000 Americans. Even though much progress has been made in MM therapy, MM remains an incurable disease for the vast majority of patients. The existence of MM stem cell is considered one of the major causes of MM drug-resistance, leading to relapse. This highlights the importance and urgency of developing approaches to target MM stem cells. However, very little is known about the molecular characteristics of the MM stem cells, which makes it difficult to target MM stem cells therapeutically. Evidence of the existence of a myeloma stem cell has been provided by Matsui et al. showing that the CD138- and CD20+ fraction, which is a minor population of the MM cells, has a greater clonogenic potential and has the phenotype of a memory B-cell (CD19+, CD27+). In this review, we report recent progress of cell surface markers in cancer stem cells, especially in myeloma and the molecular mechanisms related to drug resistance and myeloma disease progression. PMID:22432075

  12. Promoting effects of isobavachin on neurogenesis of mouse embryonic stem cells were associated with protein prenylation

    PubMed Central

    Wang, Dan-yin; Hu, Yu-zhe; Kong, Si-si; Yu, Yong-ping; Zhu, Dan-yan; Lou, Yi-jia

    2011-01-01

    Aim: Some small molecules can induce mouse embryonic stem (ES) cells to differentiate into neuronal cells. Here, we explored the effect of isobavachin (IBA), a compound with a prenyl group at position 8 of ring A, on promoting neuronal differentiation and the potential role of its protein prenylation. Methods: The hanging drop method was employed for embryonic body (EB) formation to mimic embryo development in vivo. The EBs were treated with IBA at a final concentration of 10?7 mol/L from EB stage (d 4) to d 8+10. Geranylgeranyltransferase I inhibitor GGTI-298 was subsequently used to disrupt protein prenylation. Neuronal subtypes, including neurons and astrocytes, were observed by fluorescence microscopy. Gene and protein expression levels were detected using RT-PCR and Western blot analysis, respectively. Results: With IBA treatment, nestin was highly expressed in the neural progenitors generated from EBs (d 4, d 8+0). EBs then further differentiated into neurons (marked by ?-tubulin III) and astrocytes (marked by GFAP), which were both up-regulated in a time-dependent manner on d 8+5 and d 8+10. Co-treatment with GGTI-298 selectively abolished the IBA-induced neuronal differentiation. Moreover, in the MAPK pathway, p38 and JNK phosphorylation were down-regulated, while ERK phosphorylation was up-regulated after IBA treatment at different neuronal differentiation passages. Conclusion: IBA can facilitate mouse ES cells differentiating into neuronal cells. The mechanism involved protein prenylation and, subsequently, phos-ERK activation and the phos-p38 off pathway. PMID:21441946

  13. [Protective effects of human bone marrow mesenchymal stem cells on hematopoietic organs of irradiated mice].

    PubMed

    Chen, Ling-Zhen; Yin, Song-Mei; Zhang, Xiao-Ling; Chen, Jia-Yu; Wei, Bo-Xiong; Zhan, Yu; Yu, Wei; Wu, Jin-Ming; Qu, Jia; Guo, Zi-Kuan

    2012-12-01

    The objective of this study was to explore the protective effects of human bone marrow mesenchymal stem cells (MSC) on hematopoietic organs of irradiated mice. Human bone marrow MSC were isolated, ex vivo expanded, and identified by cell biological tests. Female BALB/c mice were irradiated with (60)Co ?-ray at a single dose of 6 Gy, and received different doses of human MSC and MSC lysates or saline via tail veins. The survival of mice was record daily, and the femurs and spleens were harvested on day 9 and 16 for pathologic examination. The histological changes were observed and the cellularity was scored. The results showed that the estimated survival time of MSC- and MSC lysate-treated mice was comparable to that of controls. The hematopoiesis in the bone marrow of mice that received high-dose (5×10(6)) of MSC or MSC lysates was partially restored on day 9 and the capacity of hemopoietic tissue and cellularity scorings were significantly elevated as compared with that of controls (P < 0.05). Proliferative nudes were also obviously observed in the spleens of mice that received high-dose of MSC or MSC lysates on d 9 after irradiation. The histological structures of the spleen and bone marrow of the mice that received high-doses (5×10(6)) of MSC or MSC lysates were restored to normal, the cell proliferation displayed extraordinarily active. Further, the cellularity scores of the bone marrow were not significantly different between the high-dose MSC and MSC lysate-treated mice. It is concluded that the bone marrow MSC can promote the hematopoietic recovery of the irradiated mice, which probably is associated with the bioactive materials inherently existed in bone marrow cells. PMID:23257449

  14. Microarrayed Materials for Stem Cells

    PubMed Central

    Mei, Ying

    2013-01-01

    Stem cells hold remarkable promise for applications in disease modeling, cancer therapy and regenerative medicine. Despite the significant progress made during the last decade, designing materials to control stem cell fate remains challenging. As an alternative, materials microarray technology has received great attention because it allows for high throughput materials synthesis and screening at a reasonable cost. Here, we discuss recent developments in materials microarray technology and their applications in stem cell engineering. Future opportunities in the field will also be reviewed. PMID:24311967

  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. [Allogeneic haematopoietic stem cell transplantation - an overview].

    PubMed

    Holtick, U; Chemnitz, J M; Hallek, M; Scheid, C

    2015-05-01

    Allogeneic haematopoietic stem cell transplantation is an effective treatment option for chemotherapy-refractory or relapsed haematological malignancies such as leukaemias and lymphomas. After conditioning with chemotherapy with or without total body irradiation, donor cells are infused to reconstitute haematopoiesis. Donor-derived immune cells induce immune reactions to control or eradicate the underlying disease, thereby going beyond the effect of chemotherapy. This graft-versus-tumour effect (GvT) is often accompanied by detrimental graft-versus-host reactions (graft-versus-host disease, GvHD), which substantially influence the mortality and morbidity after transplantation. The balance between GvHD and GvT, implementing various parameters such as donor selection, stem cell source, conditioning, immune reconstitution and immunosuppressive regimens, represents the challenge in the field of allogeneic stem cell transplantation. PMID:25989032

  17. Cancer stem cell subsets and their relationships

    PubMed Central

    2011-01-01

    Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells, migrating cancer stem cells and chemoradioresistant cancer stem cells, playing different roles in cancer initiation and progression. Here we propose a new concept "horizontal hierarchy of cancer stem cells" to distinguish them from vertical hierarchy cancer stem cells, cancer transient-amplifying cells and cancer differentiated cells, and summarize our current understanding of these subsets of cancer stem cells with the aim to open up novel therapeutic strategies for cancer based on this understanding. PMID:21542915

  18. Hematopoietic Stem Cell Aging: Wrinkles In Stem Cell Potential

    Microsoft Academic Search

    S. M. Chambers; M. A. Goodell

    2007-01-01

    Hematopoietic stem cells (HSC) continuously replenish the blood and immune systems. Their activity must be sustained throughout\\u000a life to support optimal immune responses. It has been thought that stem cells may be somewhat protected from age because of\\u000a their perpetual requirement to replenish the blood, however studies over the past 10 years have revealed dramatic changes\\u000a in HSC function and phenotype

  19. Comparative effect of human platelet derivatives on proliferation and osteogenic differentiation of menstrual blood-derived stem cells.

    PubMed

    Kazemnejad, Somaieh; Najafi, Roghaieh; Zarnani, Amir Hassan; Eghtesad, Saman

    2014-03-01

    Menstrual blood has been recognized as an easily accessible and inexpensive source of stem cells, in recent years. To establish a safe and efficient protocol for development of menstrual blood-derived stem cells (MenSCs) into osteoblasts, the effect of substitution of fetal bovine serum (FBS) with human platelet derivatives (HPDs) was evaluated during proliferation and osteogenic differentiation of MenSCs. To this aim, parallel experiments were carried out on cultured MenSCs in the presence of platelet-rich plasma, platelet-poor plasma, platelet gel supernatant, or human platelet releasate (HPR), and compared with cells cultured in conventional growth medium containing FBS. There was no significant difference between growth curves of cultured MenSCs in presence of different fortified media. However, the MenSCs demonstrated variant differentiation patterns in response to FBS replacement with HPDs. Mineralization, as judged by Alizarin red staining, was significantly higher in cells differentiated in the presence of HPR compared to cells that were fortified with other medium supplements. A greater osteocalcin production level, alkaline phosphatase activity, and mRNA expression of osteogenic-specific genes in differentiated MenSCs under HPR condition further confirmed our previous findings. Based on our data, FBS substitution by HPDs not only allows for successful MenSCs proliferation, but also promotes MenSCs development into osteoblasts. The effectiveness of HPR on osteogenic differentiation of MenSCs represents an important novel step toward safe and applied stem cell therapy of bone diseases. PMID:24037410

  20. Effective Eradication of Glioblastoma Stem Cells by Local Application of an AC133/CD133-Specific T-cell-Engaging Antibody and CD8 T Cells.

    PubMed

    Prasad, Shruthi; Gaedicke, Simone; Machein, Marcia; Mittler, Gerhard; Braun, Friederike; Hettich, Michael; Firat, Elke; Klingner, Kerstin; Schüler, Julia; Wider, Dagmar; Wäsch, Ralph M; Herold-Mende, Christel; Elsässer-Beile, Ursula; Niedermann, Gabriele

    2015-06-01

    Cancer stem cells (CSC) drive tumorigenesis and contribute to genotoxic therapy resistance, diffuse infiltrative invasion, and immunosuppression, which are key factors for the incurability of glioblastoma multiforme (GBM). The AC133 epitope of CD133 is an important CSC marker for GBM and other tumor entities. Here, we report the development and preclinical evaluation of a recombinant AC133×CD3 bispecific antibody (bsAb) that redirects human polyclonal T cells to AC133(+) GBM stem cells (GBM-SC), inducing their strong targeted lysis. This novel bsAb prevented the outgrowth of AC133-positive subcutaneous GBM xenografts. Moreover, upon intracerebral infusion along with the local application of human CD8(+) T cells, it exhibited potent activity in prophylactic and treatment models of orthotopic GBM-SC-derived invasive brain tumors. In contrast, normal hematopoietic stem cells, some of which are AC133-positive, were virtually unaffected at bsAb concentrations effective against GBM-SCs and retained their colony-forming abilities. In conclusion, our data demonstrate the high activity of this new bsAb against patient-derived AC133-positive GBM-SCs in models of local therapy of highly invasive GBM. Cancer Res; 75(11); 2166-76. ©2015 AACR. PMID:25840983

  1. 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

  2. Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells on Laser-Induced Retinal Injury in Mice

    PubMed Central

    Jiang, Yuanfeng; Zhang, Yan; Zhang, Lingjun; Wang, Meiyan; Zhang, Xiaomin; Li, Xiaorong

    2014-01-01

    Stem cell therapy has shown encouraging results for neurodegenerative diseases. The retina provides a convenient locus to investigate stem cell functions and distribution in the nervous system. In the current study, we investigated the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice labeled with green fluorescent protein (GFP) were injected via the tail vein into mice after laser photocoagulation. We found that the average diameters of laser spots and retinal cell apoptosis were decreased in the MSC-treated group. Interestingly, GFP-MSCs did not migrate to the injured retina. Further examination revealed that the mRNA expression levels of glial fibrillary acidic protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC transplantation. Our results suggest that intravenously injected MSCs have the ability to inhibit retinal cell apoptosis, reduce the inflammatory response and limit the spreading of damage in the laser-injured retina of mice. Systemic MSC therapy might play a role in neuroprotection, mainly by regulation of the intraocular microenvironment. PMID:24871366

  3. Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells.

    PubMed

    Carstens, Matthew R; Fisher, Robert C; Acharya, Abhinav P; Butterworth, Elizabeth A; Scott, Edward; Huang, Emina H; Keselowsky, Benjamin G

    2015-07-14

    A new paradigm in oncology establishes a spectrum of tumorigenic potential across the heterogeneous phenotypes within a tumor. The cancer stem cell hypothesis postulates that a minute fraction of cells within a tumor, termed cancer stem cells (CSCs), have a tumor-initiating capacity that propels tumor growth. An application of this discovery is to target this critical cell population using chemotherapy; however, the process of isolating these cells is arduous, and the rarity of CSCs makes it difficult to test potential drug candidates in a robust fashion, particularly for individual patients. To address the challenge of screening drug libraries on patient-derived populations of rare cells, such as CSCs, we have developed a drug-eluting microarray, a miniaturized platform onto which a minimal quantity of cells can adhere and be exposed to unique treatment conditions. Hundreds of drug-loaded polymer islands acting as drug depots colocalized with adherent cells are surrounded by a nonfouling background, creating isolated culture environments on a solid substrate. Significant results can be obtained by testing <6% of the cells required for a typical 96-well plate. Reliability was demonstrated by an average coefficient of variation of 14% between all of the microarrays and 13% between identical conditions within a single microarray. Using the drug-eluting array, colorectal CSCs isolated from two patients exhibited unique responses to drug combinations when cultured on the drug-eluting microarray, highlighting the potential as a prognostic tool to identify personalized chemotherapeutic regimens targeting CSCs. PMID:26124098

  4. 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

  5. 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

  6. Autologous Stem Cell Transplantation Is an Effective Salvage Therapy for Primary Refractory Multiple Myeloma.

    PubMed

    Parrish, Christopher; Rahemtulla, Amin; Cavet, Jim; Pearce, Rachel M; Kirkland, Keiren; Lee, Julia; Cook, Mark; Wilson, Keith; Cook, Gordon

    2015-07-01

    High-dose therapy and autologous stem cell transplantation (ASCT) have proven efficacy in patients with multiple myeloma responding well to induction therapy. For those who fail to achieve a stable partial response (PR), the effect of ASCT is unclear. We report on 126 patients identified from a national database, who underwent ASCT having achieved effective in this group conventionally considered to have a poor outcome. Comprehensive multivariate analysis identified no disparate subgroups, meaning ASCT is a reasonable strategy for all fit primary refractory patients. PMID:25843652

  7. 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

  8. 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

  9. Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation.

    PubMed

    Zhao, Ke; Lou, Rui; Huang, Fen; Peng, Yanwen; Jiang, Zujun; Huang, Ke; Wu, Xiuli; Zhang, Yu; Fan, Zhiping; Zhou, Hongsheng; Liu, Can; Xiao, Yang; Sun, Jing; Li, Yangqiu; Xiang, Peng; Liu, Qifa

    2015-01-01

    Refractory acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic stem cell transplantation. This study evaluated the immunomodulation effects of mesenchymal stromal cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. Forty-seven patients with refractory aGVHD were enrolled: 28 patients receiving MSC and 19 patients without MSC treatment. MSCs were given at a median dose of 1 × 10(6) cells/kg weekly until patients got complete response or received 8 doses of MSCs. After 125 doses of MSCs were administered, with a median of 4 doses (range, 2 to 8) per patient, overall response rate was 75% in the MSC group compared with 42.1% in the non-MSC group (P = .023). The incidence of cytomegalovirus, Epstein-Barr virus infections, and tumor relapse was not different between the 2 groups during aGVHD treatment and follow-up. The incidence and severity of chronic GVHD in the MSC group were lower than those in the non-MSC group (P = .045 and P = .005). The ratio of CD3(+)CD4(+)/CD3(+)CD8(+) T cells, the frequencies of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), and the levels of signal joint T cell-receptor excision DNA circles (sjTRECs) after MSCs treatment were higher than those pretreatment. MSC-treated patients exhibited higher Tregs frequencies and sjTRECs levels than those in the non-MSC group at 8 and 12 weeks after treatment. MSCs derived from bone marrow of a third-party donor are effective to refractory aGVHD. It might reduce the incidence and severity of chronic GVHD in aGVHD patients by improving thymic function and induction of Tregs but not increase the risks of infections and tumor relapse. PMID:25300866

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

    PubMed Central

    2010-01-01

    Background As the strategy for tissue regeneration using mesenchymal stem cells (MSCs) for transplantation, it is necessary that MSCs be accumulated and kept in the target area. To accumulate MSCs effectively, we developed a novel technique for a magnetic targeting system with magnetically labeled MSCs and an external magnetic force. In this study, we examined the effect of an external magnetic force on magnetically labeled MSCs in terms of cell adhesion and proliferation. Methods Magnetically labeled MSCs were plated at the bottom of an insert under the influence of an external magnetic force for 1 hour. Then the inserts were turned upside down for between 1 and 24 hours, and the number of MSCs which had fallen from the membrane was counted. The gene expression of MSCs affected magnetic force was analyzed with microarray. In the control group, the same procedure was done without the external magnetic force. Results At 1 hour after the inserts were turned upside down, the average number of fallen MSCs in the magnetic group was significantly smaller than that in the control group, indicating enhanced cell adhesion. At 24 hours, the average number of fallen MSCs in the magnetic group was also significantly smaller than that in control group. In the magnetic group, integrin alpha2, alpha6, beta3 BP, intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1) were upregulated. At 1, 2 and 3 weeks after incubation, there was no statistical significant difference in the numbers of MSCs in the magnetic group and control group. Conclusions The results indicate that an external magnetic force for 1 hour enhances cell adhesion of MSCs. Moreover, there is no difference in cell proliferation after using an external magnetic force on magnetically labeled MSCs. PMID:20152029

  11. Matrix Elasticity Directs Stem Cell Lineage Specification

    E-print Network

    Discher, Dennis

    and also for therapeu- tic uses of stem cells. INTRODUCTION Adult stem cells, as part of normalMatrix Elasticity Directs Stem Cell Lineage Specification Adam J. Engler,1,2 Shamik Sen,1,2 H. Lee.06.044 SUMMARY Microenvironments appear important in stem cell lineage specification but can be difficult

  12. 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

  13. Stem Cell Research: Elephants in the Room

    Microsoft Academic Search

    NEIL D. THEISE

    2003-01-01

    hen groups of stem cell researchers meet or when stem cell researchers publish their data and interpre- tations in scientific journals, a small cluster of important issues loom over the discussions yet often go unremarked. These issues influence much of the nature, direction, and funding of stem cell investigations, particularly those in- volving adult stem cells. The unmentionable issues are

  14. Differentiation potential of adult stem cells

    Microsoft Academic Search

    Diana Clarke; Jonas Frisén

    2001-01-01

    In many different adult tissues, stem cells generate new cells either continuously or in response to injury. Such cells were thought to be limited to generating the types of cells normally present in the tissue where the stem cell resides. However, several different stem-cell populations in the adult have been found recently to be capable of generating additional cell types

  15. 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

  16. World stem cell summit 2014.

    PubMed

    Hasegawa, Kouichi; Asada, Takashi; Sengoku, Shintaro; Nakatsuji, Norio

    2015-05-01

    World Stem Cell Summit 2014 3-5 December 2014, San Antonio, TX, USA Among the many international conferences in the field of stem cells and regenerative medicine, WSCS is distinct in focusing its efforts to serve as the meeting point by multisector communities of research, clinics, industry, regulation, policy making and ethics. All are aiming at advancing stem cell innovation and new therapies, under the banner of 'connect, collaborate and cure'. As same as past years, presenters and attendees included not only researchers but also clinicians, funding agencies, government officials, industries and patients. Thus, many sessions focused on the clinical translation from basic research. Another important agenda were industrial and social aspects, and problems to be solved before realization of practical and sustainable stem cell-based therapies. PMID:26022760

  17. Controlled differentiation of stem cells?

    PubMed Central

    Hwang, Nathaniel S.; Varghese, Shyni; Elisseeff, Jennifer

    2009-01-01

    The extracellular microenvironment plays a significant role in controlling cellular behavior. Identification of appropriate biomaterials that support cellular attachment, proliferation and, most importantly in the case of human embryonic stem cells, lineage-specific differentiation is critical for tissue engineering and cellular therapy. In addition to growth factors and morphogenetic factors known to induce lineage commitment of stem cells, a number of scaffolding materials, including synthetic and naturally-derived biomaterials, have been utilized in tissue engineering approaches to direct differentiation. This review focuses on recent emerging findings and well-characterized differentiation models of human embryonic stem cells. Additionally, we also discuss about various strategies that have been used in stem cell expansion. PMID:18006108

  18. 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

  19. 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

  20. EMBRYONIC STEM CELLS or INDUCED PLURIPOTENT STEM CELLS? A DNA INTEGRITY PERSPECTIVE

    E-print Network

    Boyer, Edmond

    1 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 cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical research

  1. 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

  2. Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis.

    PubMed

    Perin, Laura; Sedrakyan, Sargis; Giuliani, Stefano; Da Sacco, Stefano; Carraro, Gianni; Shiri, Liron; Lemley, Kevin V; Rosol, Michael; Wu, Sam; Atala, Anthony; Warburton, David; De Filippo, Roger E

    2010-01-01

    Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos) stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN. PMID:20195358

  3. Protective Effect of Human Amniotic Fluid Stem Cells in an Immunodeficient Mouse Model of Acute Tubular Necrosis

    PubMed Central

    Perin, Laura; Sedrakyan, Sargis; Giuliani, Stefano; Da Sacco, Stefano; Carraro, Gianni; Shiri, Liron; Lemley, Kevin V.; Rosol, Michael; Wu, Sam; Atala, Anthony; Warburton, David; De Filippo, Roger E.

    2010-01-01

    Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kitpos stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN. PMID:20195358

  4. Pharmacologically active microcarriers influence VEGF-A effects on mesenchymal stem cell survival

    PubMed Central

    Penna, Claudia; Perrelli, Maria-Giulia; Karam, Jean-Pierre; Angotti, Carmelina; Muscari, Claudio; Montero-Menei, Claudia N; Pagliaro, Pasquale

    2013-01-01

    Resistance of transplanted mesenchymal stem cells (MSCs) in post-ischemic heart is limited by their poor vitality. Vascular-endothelial-growth-factor-A (VEGF-A) as such or slowly released by fibronectin-coated pharmacologically-active-microcarriers (FN-PAM-VEGF) could differently affect survival kinases and anti-apoptotic mediator (e.g. Bcl-2). Therefore VEGF-A or FN-PAM-VEGF could differently enhance cell proliferation, and/or resistance to hypoxia/reoxygenation (H/R) of MSCs. To test these hypotheses MSCs were incubated for 6-days with VEGF-A alone or with FN-PAM-VEGF. In addition, MSCs pre-treated for 24-hrs with VEGF-A or FN-PAM-VEGF were subsequently exposed to H/R (72-hrs 3% O2 and 3-hrs of reoxygenation). Cell-proliferation and post-hypoxic vitality were determined. Kinases were studied at 30-min., 1- and 3-days of treatment. Cell-proliferation increased about twofold (P < 0.01) 6-days after VEGF-A treatment, but by a lesser extent (55% increase) with FN-PAM-VEGF (P < 0.05). While MSC pre-treatment with VEGF-A confirmed cell-proliferation, pre-treatment with FN-PAM-VEGF protected MSCs against H/R. In the early phase of treatments, VEGF-A increased phospho-Akt, phospho-ERK-1/2 and phospho-PKC? compared to the untreated cells or FN-PAM-VEGF. Afterword, kinase phosphorylations were higher with VGEF, except for ERK-1/2, which was similarly increased by both treatments at 3 days. Only FN-PAM-VEGF significantly increased Bcl-2 levels. After H/R, lactate dehydrogenase release and cleaved Caspase-3 levels were mainly reduced by FN-PAM-VEGF. While VEGF-A enhances MSC proliferation in normoxia, FN-PAM-VEGF mainly hampers post-hypoxic MSC death. These different effects underscore the necessity of approaches suited to the various conditions. The use of FN-PAM-VEGF could be considered as a novel approach for enhancing MSC survival and regeneration in hostile environment of post-ischemic tissues. PMID:23305078

  5. 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

  6. The stem cell debate CNN

    NSDL National Science Digital Library

    2001-01-01

    As most of our readers no doubt know, President Bush made a determination on federal funding for embryonic stem cell research in August 2001, agreeing to release federal funds for research involving already existing stem cell lines. Information on this contentious topic is available at CNN's in-depth special, which features articles, analysis, video clips, and message boards devoted to the many aspects of the debate.

  7. 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.

  8. Effects of Low Level Red-light Irradiation on the Proliferation of Mesenchymal Stem Cells Derived from Rat Bone Marrow

    Microsoft Academic Search

    Wen-Tyng Li; Yao-Chu Leu

    2007-01-01

    Mesenchymal stem cells (MSCs) are capable of regenerating various mesenchymal tissues and are essential in supporting the growth and differentiation of hematopoietic stem cells within the bone marrow microenvironment in vivo. To achieve clinically meaningful numbers of cells, many approaches have been used to maintain the differentiation potentialities and expand enough cells for clinical treatments. Previously, we have reported that

  9. The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival

    Microsoft Academic Search

    Bernadette Lehner; Beatrice Sandner; Julia Marschallinger; Christine Lehner; Tanja Furtner; Sebastien Couillard-Despres; Francisco J. Rivera; Gero Brockhoff; Hans-Christian Bauer; Norbert Weidner; Ludwig Aigner

    5-Bromo-2?-deoxyuridin (BrdU) is frequently used in anaylsis of neural stem cell biology, in particular to label and to fate-map\\u000a dividing cells. However, up to now, only a few studies have addressed the question as to whether BrdU labeling per se affects\\u000a the cells to be investigated. Here, we focused on the potential impact of BrdU on neurosphere cultures derived from

  10. Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels.

    PubMed

    Zhu, Meiling; Feng, Qian; Bian, Liming

    2014-03-01

    Photocrosslinked hyaluronic acid (HA) hydrogels provide a conducive 3-D environment that supports the chondrogenesis of human mesenchymal stem cells (hMSCs). The HA macromer concentration in the hydrogels has a significant impact on the chondrogenesis of the encapsulated MSCs due to changes in the physical properties of the hydrogels. Meanwhile, hypoxia has been shown to promote MSC chondrogenesis and suppress subsequent hypertrophy. This study investigates the combinatorial effect of tuning HA macromer concentration (1.5-5%w/v) and hypoxia on MSC chondrogenesis and hypertrophy. To decouple the effect of HA concentration from that of crosslinking density, the HA hydrogel crosslinking density was adjusted by varying the extent of the reaction through the light exposure time while keeping the HA concentration constant (5%w/v at 5 or 15 min). It was found that hypoxia had no significant effect on the chondrogenesis and cartilaginous matrix synthesis of hMSCs under all hydrogel conditions. In contrast, the hypoxia-mediated positive or negative regulation of hMSC hypertrophy in HA hydrogels is dependent on the HA concentration but independent of the crosslinking density. Specifically, hypoxia significantly suppressed hMSC hypertrophy and neocartilage calcification in low HA concentration hydrogels, whereas hypoxia substantially enhanced hMSC hypertrophy, leading to elevated tissue calcification in high HA concentration hydrogels irrespective of their crosslinking density. In addition, at a constant high HA concentration, increasing hydrogel crosslinking density promoted hMSC hypertrophy and matrix calcification. To conclude, the findings from this study demonstrate that the effect of hypoxia on hMSC chondrogenesis and hypertrophy is differentially influenced by the encapsulating HA hydrogel properties. PMID:24342044

  11. Effects of 3D microwell culture on initial fate specification in human embryonic stem cells

    PubMed Central

    Hsiao, Cheston; Tomai, Matthew; Glynn, Jeremy; Palecek, Sean P.

    2014-01-01

    Several studies have demonstrated that 3D culture systems influence human embryonic stem cell (hESC) phenotypes and fate choices. However, the effect that these microenvironmental changes have on signaling pathways governing hESC behaviors is not well understood. Here, we have used a 3D microwell array to investigate differences in activation of developmental pathways between 2D and 3D cultures of both undifferentiated hESCs and hESCs undergoing initial differentiation in embryoid bodies (EBs). We observed increased induction into mesoderm and endoderm and differences in expression of genes from multiple signaling pathways that regulate development, including Wnt/?-catenin, TGF-? superfamily, Notch and FGF during EB-mediated differentiation, in 3D microwells as compared with the 2D substrates. In undifferentiated hESCs, we also observed differences in epithelial-mesenchymal transition phenotypes and the TGF?/BMP pathway between cultures in 3D and 2D. These results illustrate that 3D culture influences multiple pathways that may regulate the differentiation trajectories of hESCs. PMID:25505348

  12. 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

  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. 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

  15. Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis

    PubMed Central

    Xiao, Juan; Yang, Rongbing; Biswas, Sangita; Qin, Xin; Zhang, Min; Deng, Wenbin

    2015-01-01

    Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC) and induced pluripotent stem cell (iPSCs) derived precursor cells can modulate the autoimmune response in the central nervous system (CNS) and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS. PMID:25918935

  16. 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

  17. Demonstration of Stem Cell Inhibition and Myeloprotective Effects of SCI\\/rhMIPla In Vivo

    Microsoft Academic Search

    David J. Dunlop; Eric G. Wright; Sally Lorimore; Gerard J. Graham; Tessa Holyoake; David J. Kerr; Stephen D. Wolpe; Ian B. Pragnell

    human recombinant homologue of murine macrophage in- flammatory protein-la (rhMIPla) to suppress the prolifera- tion of primitive murine progenitors in vitro and in vivo. This recombinant protein (stem cell inhibitor, similar to the hu- man homologue of MIPla, LD78) is active in a dose- dependent manner in vitro on CFU-S measured at day 12 and to a slightly lesser extent

  18. Plasticity of spermatogonial stem cells

    PubMed Central

    Cooke, Paul S; Simon, Liz; Nanjappa, Manjunatha K; Medrano, Theresa I; Berry, Suzanne E

    2015-01-01

    There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs), and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES) cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine. PMID:25677134

  19. Biomaterials for stem cell differentiation

    Microsoft Academic Search

    Eileen Dawson; Gazell Mapili; Kathryn Erickson; Sabia Taqvi; Krishnendu Roy

    2008-01-01

    The promise of cellular therapy lies in the repair of damaged organs and tissues in vivo as well as generating tissue constructs in vitro for subsequent transplantation. Unfortunately, the lack of available donor cell sources limits its ultimate clinical applicability. Stem cells are a natural choice for cell therapy due to their pluripotent nature and self-renewal capacity. Creating reserves of

  20. Trophic Factors from Tissue Stem Cells for Renal Regeneration

    PubMed Central

    Tsuji, Kenji; Kitamura, Shinji

    2015-01-01

    Stem cell therapies against renal injury have been advancing. The many trials for renal regeneration are reported to be effective in many kinds of renal injury models. Regarding the therapeutic mechanism, it is believed that stem cells contribute to make regeneration via not only direct stem cell differentiation in the injured space but also indirect effect via secreted factors from stem cells. Direct differentiation from stem cells to renal composed cells has been reported. They differentiate to renal composed cells and make functions. However, regarding renal regeneration, stem cells are discussed to secrete many kinds of growth factors, cytokines, and chemokines in paracrine or autocrine manner, which protect against renal injury, too. In addition, it is reported that stem cells have the ability to communicate with nearby cells via microvesicle-related RNA and proteins. Taken together from many reports, many secreted factors from stem cells were needed for renal regeneration orchestrally with harmony. In this review, we focused on the effects and insights of stem cells and regenerative factors from stem cells.

  1. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy

    PubMed Central

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34+ and CD 133+ stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future.

  2. 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

  3. Multi-therapeutic effects of human adipose-derived mesenchymal stem cells on radiation-induced intestinal injury

    PubMed Central

    Chang, P; Qu, Y; Liu, Y; Cui, S; Zhu, D; Wang, H; Jin, X

    2013-01-01

    Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. However, current management of these injuries is ineffective. Recently, mesenchymal stem cells (MSCs) have been extensively used in regenerative medicine and have achieved a high level of efficacy. In the present study, we hypothesised that human adipose-derived mesenchymal stem cells (hAd-MSCs) could be used as potential tools to heal RIII. We observed that adult Sprague–Dawley rats that received whole-abdominal irradiation benefitted from hAd-MSC injection. hAd-MSCs had RIII-healing effects, including anti-inflammation, neovascularisation and maintenance of epithelium homeostasis, as indicated by elevated serum IL-10, upregulation of vascular endothelial growth factor, basic fibroblast growth factor and epidermal growth factor in irradiated intestine, mobilisation of CD31-positive haematopoietic stem cells or haematopoietic progenitor cells, and the prolonged presence of Bmi1-positive cells within crypts. Consequently, after hAd-MSC treatment, irradiated rats survived longer than non-treated animals. These results suggest that hAd-MSCs have therapeutic potential for RIII management. PMID:23788042

  4. Cell Stem Cell FoxO3 Regulates Neural Stem Cell Homeostasis

    E-print Network

    Brunet, Anne

    recently found to play an important role in NSC self-renewal by negatively regu- lating the cell cycle important implications for counteracting brain aging in long-lived species. INTRODUCTION Neural stem cellsCell Stem Cell Article FoxO3 Regulates Neural Stem Cell Homeostasis Vale´ rie M. Renault,1 Victoria

  5. Immunosuppressive effects of mesenchymal stem cell transplantation in rat burn models

    PubMed Central

    Zhang, Jinjin; La, Xiaolin; Fan, Lixing; Li, Peng; Yu, Yuanlun; Huang, Yongli; Ding, Jianbing; Xing, Yanchao

    2015-01-01

    Objective: This study is to investigate the effects of mesenchymal stem cell (MSC) transplantation in burn treatment. Methods: Wharton’s Jelly was stripped from neonatal umbilical cord, and human umbilical cord MSCs were then cultured. Burn models were constructed in male SD rats weighted at 200 ± 5 g, and the rats were randomly divided into control and MSCs transplantation groups. The rats in transplantation group were injected subcutaneously with MSCs (2×106) at 24 h after burning. Blood samples were collected at 0 d, 1 d, 2 d, 3 d, 5 d and 7 d after burning and the contents of white blood cells (WBC), C-reactive protein (CRP), interferon-? (IFN-?), tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6) and interleukin-10 (IL-10 ) were detected. The wound healing rate at 7 d, 14 d, 21 d and 28 d together with the wound healing time were compared and analyzed statistically by analysis of variance (ANOVA). Results: WBC and CRP in control group increased significantly at 1 d and 2 d, 2 d and 3 d, respectively. IFN-?, IL-6 and IL-10 levels in serum showed increasing till 5th day and TNF-? arrived its peak value at 7th day. By contrast, WBC, CRP, TNF-?, IL-6 and IL-10 in the MSCs transplantation group showed slight increase after burning and the differences were verified by statistically analysis. IFN-? showed no significant difference between the two groups. MSCs transplantation group showed significantly higher wound healing rate at 14 d, 21 d, 28 d and showed shorter wound healing time than control. Conclusions: MSCs transplantation could suppress secondary inflammatory reaction by lowering inflammatory cytokines after burning, thus promoting wound healing and scald repair in burn animal model.

  6. Effects of hydroxyapatite in 3-D chitosan–gelatin polymer network on human mesenchymal stem cell construct development

    Microsoft Academic Search

    Feng Zhao; Warren L. Grayson; Teng Ma; Bruce Bunnell; William W. Lu

    2006-01-01

    Human mesenchymal stem cells (hMSCs) have great potential in bone tissue engineering, and hydroxyapatite (HA), a natural component of human hard tissues, is believed to support hMSC growth and osteogenic differentiation. In this study, two types of biomimetic composite materials, chitosan–gelatin (CG) and hydroxyapatite\\/chitosan–gelatin (HCG), were fabricated and compared to examine the effects of HA on hMSC adhesion and 3-D

  7. Ferreting out stem cells from their niches

    Microsoft Academic Search

    Valerie Horsley; Elaine Fuchs

    2011-01-01

    Over the past decade, it has become increasingly clear that many tissues have regenerative capabilities. The challenge has been to find the stem cells or progenitors that are responsible for tissue renewal and repair. The revolution in technological advances that permit sophisticated spatial, temporal and kinetic analyses of stem cells has allowed stem cell hunters to ferret out where stem

  8. Dendritic Cells Loaded with Pancreatic Cancer Stem Cells (CSCs) Lysates Induce Antitumor Immune Killing Effect In Vitro

    PubMed Central

    Yin, Tao; Shi, Pengfei; Gou, Shanmiao; Shen, Qiang; Wang, Chunyou

    2014-01-01

    According to the cancer stem cells (CSCs) theory, malignant tumors may be heterogeneous in which a small population of CSCs drive the progression of cancer. Because of their intrinsic abilities, CSCs may survive a variety of treatments and then lead to therapeutic resistance and cancer recurrence. Pancreatic CSCs have been reported to be responsible for the malignant behaviors of pancreatic cancer, including suppression of immune protection. Thus, development of immune strategies to eradicate pancreatic CSCs may be of great value for the treatment of pancreatic cancer. In this study, we enriched pancreatic CSCs by culturing Panc-1 cells under sphere-forming conditions. Panc-1 CSCs expressed low levels of HLA-ABC and CD86, as measured by flow cytometry analysis. We further found that the Panc-1 CSCs modulate immunity by inhibiting lymphocyte proliferation which is promoted by phytohemagglutinin (PHA) and anti-CD3 monoclonal antibodies. The monocyte derived dendritic cells (DCs) were charged with total lysates generated from Panc-1 CSCs obtained from tumor sphere culturing. After co-culturing with lymphocytes at different ratios, the Panc-1 CSCs lysates modified DC effectively promoted lymphocyte proliferation. The activating efficiency reached 72.4% and 74.7% at the ratios of 1?10 and 1?20 with lymphocytes. The activated lymphocytes secreted high levels of INF-? and IL-2, which are strong antitumor cytokines. Moreover, Panc-1 CSCs lysates modified DC induced significant cytotoxic effects of lymphocytes on Panc-1 CSCs and parental Panc-1 cells, respectively, as shown by lactate dehydrogenase (LDH) assay. Our study demonstrates that the development of CSCs-based vaccine is a promising strategy for treating pancreatic cancer. PMID:25521461

  9. The effect of moderately halophilic bacteria supernatant on proliferation and apoptosis of cancer cells and mesenchymal stem cells.

    PubMed

    Sarvari, S; Seyedjafari, E; Amoozgar, M A; Bakhshandeh, B

    2015-01-01

    Many drug discoveries and developing of their applications has originated from microbial metabolites. The most efforts in development of new drugs are concerned with anti—cancer agents that cause better treatment results, less side effects, and more economical production. Several anti—tumor drugs have been recently extracted from natural microbial products. Among these various microbial diversity, Marin bacteria and Archaea have been considered as important and efficient organisms to serve as manufacturers of diverse bioactive compounds. Moderately halophilic microorganisms isolated from saline ponds and lakes of Iran show high capability for production of bioactive compounds like enzymes, dyes and anti—cancer agents. In this research, nine moderately halophilic bacteria isolates were screened to evaluate their anti—cancer agent productivity. After five days of culture on suitable mediums, supernatant samples were tested for in vitro anti—proliferative activity against Human Umbilical Vein Endothelial Cells (HUVEC) while same concentrations of supernatants were examined for evaluating of proliferative activity against Adipose—derived Mesenchymal stem cells (MSCs). Both assessments were carried out by MTT assay and double PI and DAPI staining. GASX17, GBWy6 and GBPX3 isolates just induced HUVEC cell deaths and exhibited anti—proliferative activity while R2S12 not only reduced HUVEC cell proliferation but also enhanced proliferation of MSCs. R2S12 , GASX17, GBWy6 and GBPX3 isolates were characterized biochemically and six hydrophilic components were detected. This research established new bioactive compounds that could be used as an effective treatment in chemotherapy. PMID:26068916

  10. Therapeutic effects of intrabone and systemic mesenchymal stem cell cytotherapy on myeloma bone disease and tumor growth

    PubMed Central

    Li, Xin; Ling, Wen; Khan, Sharmin; Yaccoby, Shmuel

    2012-01-01

    The cytotherapeutic potential of mesenchymal stem cells (MSCs) has been evaluated in various disorders including those involving inflammation, autoimmunity, bone regeneration, and cancer. Multiple myeloma (MM) is a systemic malignancy associated with induction of osteolytic lesions that often are not repaired even after prolonged remission. The aims of the study were to evaluate the effects of intrabone and systemic injections of mesenchymal stem cells (MSCs) on MM bone disease, tumor growth, and tumor regrowth in the SCID-rab model and to shed light on the exact localization of systemically injected MSCs. Intrabone injection of MSCs, but not hematopoietic stem cells, into myelomatous bones prevented MM-induced bone disease, promoted bone formation, and inhibited MM growth. After remission was induced with melphalan treatment, intrabone-injected MSCs promoted bone formation and delayed myeloma cell regrowth in bone. Most intrabone or systemically injected MSCs were undetected 2–4 weeks after injection. The bone-building effects of MSCs were mediated through activation of endogenous osteoblasts and suppression of osteoclast activity. While a single intravenous injection of MSCs had no effect on MM, sequential weekly intravenous injections of MSCs prevented MM-induced bone disease but had no effect on tumor burden. MSCs expressed high levels of anti-inflammatory (e.g. HMOX1), and bone remodeling (e.g. Decorin, CYR61) mediators. In vitro, MSCs promoted osteoblast maturation and suppressed osteoclast formation, and these effects were partially prevented by blocking decorin. A subset of intravenously or intracardially injected MSCs trafficked to myelomatous bone in SCID-rab mice. While the majority of intravenously injected MSCs were trapped in lungs, intracardially injected MSCs were mainly localized in draining mesenteric lymph nodes. This study shows that exogenous MSCs act as bystander cells to inhibit MM-induced bone disease and tumor growth and that systemically injected MSCs are attracted to bone by myeloma cells or conditions induced by MM and inhibit bone disease. PMID:22460389

  11. 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

  12. Effects of pulsed electromagnetic field on differentiation of HUES-17 human embryonic stem cell line.

    PubMed

    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

  13. The Therapeutic Effects of Human Mesenchymal Stem Cells Primed with Sphingosine-1 Phosphate on Pulmonary Artery Hypertension.

    PubMed

    Kang, Hyunsook; Kim, Kang-Hyun; Lim, Jisun; Kim, You-Sun; Heo, Jinbeom; Choi, Jongjin; Jeong, Jaeho; Kim, YongHwan; Kim, Seong Who; Oh, Yeon-Mok; Choo, Myung-Soo; Son, Jaekyoung; Kim, Su Jung; Yoo, Hyun Ju; Oh, Wonil; Choi, Soo Jin; Lee, Sei Won; Shin, Dong-Myung

    2015-07-15

    Stem cell (SC) therapy has become a potential treatment modality for pulmonary artery hypertension (PAH), but the efficacy of human SC and priming effects have not yet been established. The mobilization and homing of hematopoietic stem cells (HSCs) are modulated by priming factors that include a bioactive lipid, sphingosine-1-phosphate (S1P), which stimulates CXCR4 receptor kinase signaling. Here, we show that priming human mesenchymal stem cells (MSCs) with S1P enhances their therapeutic efficacy in PAH. Human MSCs, similar to HSCs, showed stronger chemoattraction to S1P in transwell assays. Concomitantly, MSCs treated with 0.2??M S1P showed increased phosphorylation of both MAPKp42/44 and AKT protein compared with nonprimed MSCs. Furthermore, S1P-primed MSCs potentiated colony forming unit-fibroblast, anti-inflammatory, and angiogenic activities of MSCs in culture. In a PAH animal model induced by subcutaneously injected monocrotaline, administration of human cord blood-derived MSCs (hCB-MSCs) or S1P-primed cells significantly attenuated the elevated right ventricular systolic pressure. Notably, S1P-primed CB-MSCs, but not unprimed hCB-MSCs, also elicited a significant reduction in the right ventricular weight ratio and pulmonary vascular wall thickness. S1P-primed MSCs enhanced the expression of several genes responsible for stem cell trafficking and angiogenesis, increasing the density of blood vessels in the damaged lungs. Thus, this study demonstrates that human MSCs have potential utility for the treatment of PAH, and that S1P priming increases the effects of SC therapy by enhancing cardiac and vascular remodeling. By optimizing this protocol in future studies, SC therapy might form a basis for clinical trials to treat human PAH. PMID:25761906

  14. The Extracellular Environment's Effect on Cellular Processes: An In Vitro Study of Mechanical and Chemical Cues on Human Mesenchymal Stem Cells and C17.2 Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Casey, Meghan E.

    Stem cells are widely used in the area of tissue engineering. The ability of cells to interact with materials on the nano- and micro- level is important in the success of the biomaterial. It is well-known that cells respond to their micro- and nano-environments through a process termed chemo-mechanotransduction. It is important to establish standard protocols for cellular experiments, as chemical modifications to maintenance environments can alter long-term research results. In this work, the effects of different media compositions on human mesenchymal stem cells (hMSCs) throughout normal in vitro maintenance are investigated. Changes in RNA regulation, protein expression and proliferation are studied via quantitative polymerase chain reaction (qPCR), immunocytochemistry (ICC) and cell counts, respectively. Morphological differences are also observed throughout the experiment. Results of this study illustrate the dynamic response of hMSC maintenance to differences in growth medium and passage number. These experiments highlight the effect growth medium has on in vitro experiments and the need of consistent protocols in hMSC research. A substantial opportunity exists in neuronal research to develop a material platform that allows for both the proliferation and differentiation of stem cells into neurons and the ability to quantify the secretome of neuronal cells. Anodic aluminum oxide (AAO) membranes are fabricated in a two-step anodization procedure where voltage is varied to control the pore size and morphology of the membranes. C17.2 neural stem cells are differentiated on the membranes via serum-withdrawal. Cellular growth is characterized by scanning electron microscopy (SEM), ICC and qPCR. ImageJ software is used to obtain phenotypic cell counts and neurite outgrowth lengths. Results indicate a highly tunable correlation between AAO nanopore sizes and differentiated cell populations. By selecting AAO membranes with specific pore size ranges, control of neuronal network density and neurite outgrowth length is achievable. To understand differentiation marker expressions in C17.2 NSCs and how material stiffness affects differentiation, cells are cultured on substrates of varying stiffness. qPCR is used to analyze neural stem cell, neural progenitor cell, neuron-restricted progenitor and differentiated post-mitotic neuronal cell RNA expression. Results suggest a relationship between material stiffness and neuronal development in C17.2 neural stem cells.

  15. The therapeutic effect of mesenchymal stem cell transplantation in experimental autoimmune encephalomyelitis is mediated by peripheral and central mechanisms.

    PubMed

    Morando, Sara; Vigo, Tiziana; Esposito, Marianna; Casazza, Simona; Novi, Giovanni; Principato, Maria Cristina; Furlan, Roberto; Uccelli, Antonio

    2012-01-01

    Stem cells are currently seen as a treatment for tissue regeneration in neurological diseases such as multiple sclerosis, anticipating that they integrate and differentiate into neural cells. Mesenchymal stem cells (MSCs), a subset of adult progenitor cells, differentiate into cells of the mesodermal lineage but also, under certain experimental circumstances, into cells of the neuronal and glial lineage. Their clinical development, however, has been significantly boosted by the demonstration that MSCs display significant therapeutic plasticity mainly occurring through bystander mechanisms. These features have been exploited in the effective treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis where the inhibition of the autoimmune response resulted in a significant amelioration of disease and decrease of demyelination, immune infiltrates and axonal loss. Surprisingly, these effects do not require MSCs to engraft in the central nervous system but depend on the cells' ability to inhibit pathogenic immune responses both in the periphery and inside the central nervous system and to release neuroprotective and pro-oligodendrogenic molecules favoring tissue repair. These results paved the road for the utilization of MSCs for the treatment of multiple sclerosis. PMID:22277374

  16. Effects of GSK3 inhibitors on in vitro expansion and differentiation of human adipose-derived stem cells into adipocytes

    Microsoft Academic Search

    Laure-Emmanuelle Zaragosi; Brigitte Wdziekonski; Coralie Fontaine; Phi Villageois; Pascal Peraldi; Christian Dani

    2008-01-01

    BACKGROUND: Multipotent stem cells exist within adipose tissue throughout life. An abnormal recruitment of these adipose precursor cells could participate to hyperplasia of adipose tissue observed in severe obesity or to hypoplasia of adipose tissue observed in lipodystrophy. Therefore, pharmacological molecules that control the pool of stem cells in adipose tissue are of great interest. Glycogen Synthase Kinase (GSK) 3

  17. 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

  18. [Allogenic stem cell transplantation after non-myeloablative conditioning regimen (mini-allogenic" stem cell transplantation)].

    PubMed

    Milpied, N

    2002-02-01

    Allogeneic stem cell transplantation is able to cure many hematologic malignancies, through, at least partially, a graft versus disease effect of the donor's immune system transfer. However, the toxicity of this technique limits its use to selected patients. The aim of non-myeloablative stem cell transplantation is to reduce the toxicity of the conditioning regimen while allowing the engrafement of donor's stem cells and the immunological antitumoral activity of the donor's immune system. Several reports have already demonstrated the validity of this concept. This new multi-step therapeutic strategy is complex, raises many questions and deserves further studies to be fully applicable to a greater number of patients. PMID:11873629

  19. 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

  20. 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

  1. Stem cell differentiation: Sticky mechanical memory

    NASA Astrophysics Data System (ADS)

    Eyckmans, Jeroen; Chen, Christopher S.

    2014-06-01

    Physical cues from the extracellular environment influence the lineage commitment of stem cells. Now, experiments on human mesenchymal stem cells cultured on photodegradable hydrogels show that the cells' fate can also be determined by past physical environments.

  2. 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 ...

  3. Tumour stem cells and drug resistance

    Microsoft Academic Search

    Tito Fojo; Susan Bates; Michael Dean

    2005-01-01

    The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters

  4. Self-Renewal of Stem Cells

    PubMed Central

    Vorotelyak, Ye.A.; Vasiliev, A.V.

    2009-01-01

    Asymmetric division is one of the most fundamental characteristics of adult stem cells , which ensures one daughter cell maintains stem cell status and the other daughter cell becomes committed to differentiation. New data emerged recently that allow us to conclude that asymmetric division has another important aspect: it enables self-maintenance of stem cells. PMID:22649603

  5. Using Embryonic Stem Cells as a Novel Model to Compare the Toxicological Effects of Harm Reduction and Conventional Cigarette Smoke on Early Embryo Development

    E-print Network

    Lin, Sabrina Chia-Chin

    2010-01-01

    wanting to develop stem cell research in their labs. These20 years of research using mouse embryonic stem cell lines.research effort in regenerative medicine evolves, improved protocols for differentiating stem cells

  6. 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

  7. Cultured stem cells are sensitive to gravity changes

    Microsoft Academic Search

    L. B. Buravkova; Yu. A. Romanov; N. A. Konstantinova; S. V. Buravkov; Yu. G. Gershovich; I. A. Grivennikov

    2008-01-01

    Stem and precursor cells play an important role in development and regeneration. The state of these cells is regulated by biochemical substances, mechanical stimuli and cellular interactions. To estimate gravity effects we used two types of cultured stem cells: human mesenchymal stromal cells (hMSCs) from bone marrow and mice embryonic stem (mESC) line R1. Gravity changes were simulated by long-term

  8. Improved Embryonic Stem Cell Technologies

    Microsoft Academic Search

    J. S. Draper; A. Nagy

    Murine embryonic stem (ES) cells have become an indispensable tool for investigating genetic function both in vitro and, importantly, in vivo. Recent advances, including tetraploid aggregation, new site-specific recombinases and RNAi, have enabled more sophisticated manipulation of the ES cell genome. For instance, it is now possible to control gene expression in both a temporally and spatially restricted manner. Such

  9. 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

  10. 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.

  11. 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

  12. 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

  13. Stem Cell Therapy in Neonatal Diseases.

    PubMed

    Gheorghe, Ciprian P; Bhandari, Vineet

    2015-07-01

    Common complications in neonates occur in almost every organ system in the neonatal intensive care unit. While a number of them have short-term effects, a few of them also have long-term consequences. Among the latter are bronchopulmonary dysplasia and necrotizing enterocolitis in premature neonates, and hypoxic ischemic encephalopathy in borderline preterm and term neonates. While medical advances have improved our understanding of the pathogenesis, therapies to effectively prevent and/or significantly ameliorate the severity of these disorders, and to decrease their associated mortality and morbidity have not been found. One promising approach to make a potential impact in the outcomes of these neonatal conditions is the use stem cells, specifically, mesenchymal stem cells. The authors briefly review the potential role of stem cell therapy in the above-mentioned neonatal diseases. They focus primarily on human clinical trials. PMID:25804318

  14. The effects of repetitive transcranial magnetic stimulation on proliferation and differentiation of neural stem cells

    PubMed Central

    Abbasnia, Keramatollah; Ghanbari, Amir; Abedian, Mehrnaz; Ghanbari, Ali; Sharififar, Sharareh

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is a new method for treating many neurological conditions; however, the exact therapeutic mechanisms behind rTMS-induced plasticity are still unknown. Neural stem and progenitor cells (NS/PCs) are active players in brain regeneration and plasticity but their behavior in the context of rTMS therapy needs further elucidation. We aimed to evaluate the effects of rTMS on proliferation and differentiation of NS/PCs in the subventricular zone (SVZ) of adult mouse brain. Adult male mice (n=30) were divided into rTMS (1-Hz and 30-Hz) and sham groups and treated for 7 or 14 consecutive days. Harvested NS/PCs from the SVZ were cultured in the neurosphere assay for 8 days and the number and size of the resulting neurospheres as well as their in vitro differentiation capacity were evaluated. After one week of rTMS treatment at 1-Hz and 30-Hz compared with sham stimulation, the mean neurosphere forming frequency per brain was not different while this measure significantly increased after two weeks (P<0.05). The mean neurosphere diameter in 1-Hz treatment paradigm was significantly larger compared with sham stimulation at both 1 and 2 weeks. In contrast, 30-Hz treatment paradigm resulted in significantly larger neurospheres only after 2 weeks. Importantly, rTMS treatment at both frequencies increased neuronal differentiation of the harvested NS/PCs. Furthermore, one week in vitro rTMS treatment of NS/PCs with both 1-Hz and 30-Hz increased NS/PCs proliferation and neuronal differentiation. It is concluded that both 1-Hz and 30-Hz rTMS treatment increase NS/PCs proliferation and neuronal differentiation. PMID:26140221

  15. The effects of repetitive transcranial magnetic stimulation on proliferation and differentiation of neural stem cells.

    PubMed

    Abbasnia, Keramatollah; Ghanbari, Amir; Abedian, Mehrnaz; Ghanbari, Ali; Sharififar, Sharareh; Azari, Hassan

    2015-06-01

    Repetitive transcranial magnetic stimulation (rTMS) is a new method for treating many neurological conditions; however, the exact therapeutic mechanisms behind rTMS-induced plasticity are still unknown. Neural stem and progenitor cells (NS/PCs) are active players in brain regeneration and plasticity but their behavior in the context of rTMS therapy needs further elucidation. We aimed to evaluate the effects of rTMS on proliferation and differentiation of NS/PCs in the subventricular zone (SVZ) of adult mouse brain. Adult male mice (n=30) were divided into rTMS (1-Hz and 30-Hz) and sham groups and treated for 7 or 14 consecutive days. Harvested NS/PCs from the SVZ were cultured in the neurosphere assay for 8 days and the number and size of the resulting neurospheres as well as their in vitro differentiation capacity were evaluated. After one week of rTMS treatment at 1-Hz and 30-Hz compared with sham stimulation, the mean neurosphere forming frequency per brain was not different while this measure significantly increased after two weeks (P<0.05). The mean neurosphere diameter in 1-Hz treatment paradigm was significantly larger compared with sham stimulation at both 1 and 2 weeks. In contrast, 30-Hz treatment paradigm resulted in significantly larger neurospheres only after 2 weeks. Importantly, rTMS treatment at both frequencies increased neuronal differentiation of the harvested NS/PCs. Furthermore, one week in vitro rTMS treatment of NS/PCs with both 1-Hz and 30-Hz increased NS/PCs proliferation and neuronal differentiation. It is concluded that both 1-Hz and 30-Hz rTMS treatment increase NS/PCs proliferation and neuronal differentiation. PMID:26140221

  16. Effects of Immunosuppressive Drugs on Viability and Susceptibility of Adipose- and Bone Marrow-Derived Mesenchymal Stem Cells

    PubMed Central

    Tsuji, Wakako; Schnider, Jonas T.; McLaughlin, Meghan M.; Schweizer, Riccardo; Zhang, Wensheng; Solari, Mario G.; Rubin, J. Peter; Marra, Kacey G.; Plock, Jan A.; Gorantla, Vijay S.

    2015-01-01

    The immunomodulatory potential of cell therapies using adipose-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) has been studied in vascularized composite allotransplantation (VCA). Most cell therapy-based experimental and clinical protocols integrate some degree of recipient conditioning/induction with antibodies or other immunosuppressive agents. We investigated the susceptibility of ASCs and BM-MSCs to anti-lymphocyte serum (ALS) and tacrolimus. Rat ASCs and BM-MSCs were exposed to varying concentrations of tacrolimus and ALS in vitro. Serum from ALS-treated animals was added to cell cultures. Viability, susceptibility, and cytotoxicity parameters were evaluated. ALS inhibited ASC and BM-MSC viability and susceptibility in vitro in a dose-dependent manner. ASCs were more susceptible to both ALS and tacrolimus than BM-MSCs. Trypsinized and adherent ASCs were significantly smaller than BM-MSCs. This is the first report on the viability and susceptibility characteristics of BM-MSCs or ASCs to collateral effects of ALS and tacrolimus. These in vitro insights may impact choice of cell type as well as concomitant conditioning agents and the logistical coordination of the timing, dosing, and frequency of drug or cell therapy in solid organ transplantation or VCA protocols. PMID:25932028

  17. 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

  18. Stem Cells: It's Good To Have Choices

    PubMed Central

    Bellayr, Ian H.; Li, Yong

    2009-01-01

    Three types of stem cells, embryonic, adult, and induced pluripotent stem cells, are currently studied by scientists. Barack Obama's presidency has opened the door for stem cell research by revoking statements and orders made during the former President Bush's administration. This provisional period will allow the National Institute of Health to rewrite policies governing how federal funds are distributed for stem cell research. These new regulations will grant more freedom to researchers wishing to use stem cells in their research and challenge them to determine the most appropriate stem cell treatment for a given disorder. PMID:20161527

  19. 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.

  20. Hypoxia and Stem Cell-Based Engineering of Mesenchymal Tissues

    PubMed Central

    Ma, Teng; Grayson, Warren L.; Fröhlich, Mirjam; Vunjak-Novakovic, Gordana

    2009-01-01

    Stem cells have the ability for prolonged self-renewal and differentiation into mature cells of various lineages, which makes them important cell sources for tissue engineering applications. Their remarkable ability to replenish and differentiate in vivo is regulated by both intrinsic and extrinsic cellular mechanisms. The anatomical location where the stem cells reside, known as the “stem cell niche or microenvironment,” provides signals conducive to the maintenance of definitive stem cell properties. Physiological condition including oxygen tension is an important component of the stem cell microenvironment and has been shown to play a role in regulating both embryonic and adult stem cells. This review focuses on oxygen as a signaling molecule and the way it regulates the stem cells' development into mesenchymal tissues in vitro. The physiological relevance of low oxygen tension as an environmental parameter that uniquely benefits stem cells' expansion and maintenance is described along with recent findings on the regulatory effects of oxygen on embryonic stem cells and adult mesenchymal stem cells. The relevance to tissue engineering is discussed in the context of the need to specifically regulate the oxygen content in the cellular microenvironment in order to optimize in vitro tissue development. PMID:19198002

  1. 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

  2. Multipotent somatic stem cells contribute to the stem cell niche in the Drosophila testis

    Microsoft Academic Search

    Justin Voog; Cecilia D'Alterio; D. Leanne Jones

    2008-01-01

    Adult stem cells reside in specialized microenvironments, or niches, that have an important role in regulating stem cell behaviour. Therefore, tight control of niche number, size and function is necessary to ensure the proper balance between stem cells and progenitor cells available for tissue homeostasis and wound repair. The stem cell niche in the Drosophila male gonad is located at

  3. 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://creativecommons.org/licenses/by-nc-nd/3.0/). SUMMARY Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell- surface receptor GRP78 as regulators of stem cell

  4. Stem cell aging in the Drosophila ovary

    Microsoft Academic Search

    Morris Waskar; Yishi Li; John Tower

    2005-01-01

    Accumulating evidence suggests that with time human stem cells may become defective or depleted, thereby contributing to aging\\u000a and aging-related diseases. Drosophila provides a convenient model system in which to study stem cell aging. The adult Drosophila ovary contains two types of stem cells: the germ-line stem cells give rise to the oocyte and its supporting nurse cells,\\u000a while the

  5. 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

  6. 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

  7. --Taking STem Cell SCienCe from

    E-print Network

    Bieber, Michael

    -- Taking STem Cell SCienCe from Theory To TherapieS While The healing poTenTial of STem Cell 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

  8. 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

  9. Controls of Germline Stem Cells, Entry into

    E-print Network

    Kimble, Judith

    reserved 1081-0706/07/1110-0405$20.00 Key Words stem cell niche, mitosis/meiosis decision, Notch signaling stem cell main- tenance, the cell cycle transition from mitosis to meiosis, and the choice of sexual. . . . . . . . . . . . . . . . . . . . . . . . . . . . 414 REGULATORS OF GERMLINE STEM CELL MAINTENANCE AND THE MITOSIS/MEIOSIS DECISION

  10. The hematopoietic stem cell in its place

    Microsoft Academic Search

    Gregor B Adams; David T Scadden

    2006-01-01

    A signature characteristic of stem cells is their ability to self-renew, affording a theoretically limitless ability to produce daughter cells and their descendents. This near-timeless dimension of stem cell function is not free of the constraints of place. The idea that highly specialized 'microenvironmental' cues participate in the regulation of stem cells has evidence in classic embryology and more recently

  11. Generalized Potential of Adult Neural Stem Cells

    Microsoft Academic Search

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

    2000-01-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation

  12. 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

  13. *Institute for Stem Cell Research, GSF --National

    E-print Network

    Cai, Long

    *Institute for Stem Cell Research, GSF -- National Research Center for Environment and Health neural stem cells. THE CELL BIOLOGY OF NEUROGENESIS Magdalena Götz* and Wieland B. Huttner Abstract | During the development of the mammalian central nervous system, neural stem cells and their derivative

  14. Effect of splenectomy on pancytopenia after a peripheral blood stem cell transplantation.

    PubMed

    Ding, Jiahua; Bao, Wen; Wang, Jun; Zhao, Gang; Chen, Jian; Song, Huihui

    2011-01-01

    To analyze the effect of a splenectomy on pancytopenia after a peripheral blood stem cell transplantation (PBSCT) in chronic myeloid leukemia (CML) patients. Three CML patients diagnosed with splenomegaly in our department from 2002 to 2006 received a splenectomy after PBSCT. Patient 1, a 42-year-old male in chronic phase (CP), received an HLA-identical sibling allo-PBSCT. Patient 2, a 28-year-old female in aggressive phase (AP), received a PBSCT from her twin. Patient 3, a 26-year-old male in chronic phase (CP), received a PBSCT from an unrelated donor. The conditioning regimen included busulfan and cyclophosphamide (BU/CY2). Patients 1, 2, and 3 received splenectomies on days 168, 51, and 114, respectively. Bcr-abl transcripts were detected using the polymerase chain reaction (PCR). Chimerism was documented by PCR amplification of a variable number of tandem repeat (VNTR) polymorphrisms. Neither metrisone (2 mg/kg/day for 7 days), mycophenolic acid (MMF) (0.5 g twice daily for 1 month), high-dose ?-globulin (0.4 g/kg/day for 5 days), granulocyte colony-stimulating factor (G-CSF) therapy, nor erythropoietin (EPO) therapy had produced post-PBSCT hematopoiesis recovery. Patients 1 and 2 had 5% Ph-positive chromosomes while patient 3 exhibited graft-versus-host disease (GVHD). After receiving the splenectomy, all three had a rapid hematopoeitic recovery with no evidence of Ph-positive chromosomes, and patients 1 and 3 showed complete donor chimerism (CDC). Patient 1 developed chronic GVHD (cGVHD) on day 210 postsplenectomy that was treated successfully with prednisone. Patient 2 had acute GVHD on day 55 that was treated successfully with dexamethasone (10 mg), administered intravenously once a day for 3 days with good clinical response. To date, patients 1, 2, and 3 have survived postprocedure for 85, 49, and 25 months, respectively. Splenectomy is an effective option for the patients who have pancytopenia after PBSCT and the patients recovered a good graft function after splenectomy without procedure-related complication and with long-time survival. GVHD can develop in both allo-PBSCT and syngeneic PBSCT. A splenectomy after PBSCT may increase the risk of GVHD, enhance the effect of graft versus leukemia (GVL), promote CDC formation. PMID:21092413

  15. Mesenchymal stem cells: a new trend for cell therapy

    PubMed Central

    Wei, Xin; Yang, Xue; Han, Zhi-peng; Qu, Fang-fang; Shao, Li; Shi, Yu-fang

    2013-01-01

    Mesenchymal stem cells (MSCs), the major stem cells for cell therapy, have been used in the clinic for approximately 10 years. From animal models to clinical trials, MSCs have afforded promise in the treatment of numerous diseases, mainly tissue injury and immune disorders. In this review, we summarize the recent opinions on methods, timing and cell sources for MSC administration in clinical applications, and provide an overview of mechanisms that are significant in MSC-mediated therapies. Although MSCs for cell therapy have been shown to be safe and effective, there are still challenges that need to be tackled before their wide application in the clinic. PMID:23736003

  16. The effect of beta-xylosides on the chondrogenic differentiation of mesenchymal stem cells.

    PubMed

    Li, Siyuan; Hayes, Anthony J; Caterson, Bruce; Hughes, Clare E

    2013-01-01

    Chondroitin/dermatan sulphate (CS/DS) sulphation motifs on cell and extracellular matrix proteoglycans (PGs) within stem/progenitor cell niches are involved in modulating cell phenotype during the development of many musculoskeletal connective tissues. Here, we investigate the importance of CS/DS chains and their motifs in the chondrogenic differentiation of bone marrow mesenchymal stem cells (bMSCs), using p-nitrophenyl xyloside (PNPX) as a competitive acceptor of CS/DS substitution on PGs. Comparison of cultures grown in control chondrogenic medium, with those grown in the presence of PNPX showed that PNPX delayed the onset of chondrogenesis, characterised by cell rounding and aggregation into spheroidal beads. PNPX reduced gene expression of SOX-9, aggrecan and collagen type II, and caused reduced levels of collagen type II protein. PNPX-treated cultures also showed delayed expression of a native CS/DS sulphation motif epitope recognised by antibody 6C3. This epitope appeared associated with a range of PGs, particularly biglycan, and its close association was lost after PNPX treatment. Overall our data show that perturbation of PG glycosylation with CS/DS GAGs using PNPX significantly delays the onset of chondrogenic differentiation of bMSCs, highlighting the importance of CS/DS during the initial stages of chondrogenesis. The delayed expression of the CS/DS sulphation motif recognised by 6C3 suggests that this motif, in particular, may have early involvement in chondrogenesis. The mechanism(s) by which CS/DS chains on PGs contribute to early chondrogenic events is unknown; however, they may be involved in morphogenetic signalling through the capture and cellular presentation of soluble bioactive molecules (e.g. growth factors). PMID:22910844

  17. Effects of cyclic stretch on proliferation of mesenchymal stem cells and their differentiation to smooth muscle cells

    SciTech Connect

    Ghazanfari, Samane [Cardiovascular Engineering Lab., Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of) [Cardiovascular Engineering Lab., Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad, E-mail: tafazoli@aut.ac.ir [Cardiovascular Engineering Lab., Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of)] [Cardiovascular Engineering Lab., Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of)] [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of)

    2009-10-23

    Bone marrow mesenchymal stem cells (MSCs) are capable of differentiating into a variety of cell types such as vascular smooth muscle cells (SMCs). In this study, we investigated influence of cyclic stretch on proliferation of hMSCs for different loading conditions, alignment of actin filaments, and consequent differentiation to SMCs. Isolated cells from bone marrow were exposed to cyclic stretch utilizing a customized device. Cell proliferation was examined by MTT assay, alignment of actin fibers by a designed image processing code, and cell differentiation by fluorescence staining. Results indicated promoted proliferation of hMSCs by cyclic strain, enhanced by elevated strain amplitude and number of cycles. Such loading regulated smooth muscle {alpha}-actin, and reoriented actin fibers. Cyclic stretch led to differentiation of hMSCs to SMCs without addition of growth factor. It was concluded that applying appropriate loading treatment on hMSCs could enhance proliferation capability, and produce functional SMCs for engineered tissues.

  18. Modulation of Stem Cell Differentiation with Biomaterials

    PubMed Central

    Jang, Hyeon-Ki; Kim, Byung-Soo

    2010-01-01

    Differentiation of stem cells can be controlled with interactions with microenvironments of the stem cells. The interactions contain various signals including soluble growth factor signal, cell adhesion signal, and mechanical signal, which can modulate differentiation of stem cells. Biomaterials can provide these types of signals to induce desirable cellular differentiation. Biomaterials can deliver soluble growth factors locally to stem cells at a controlled rate for a long period. Stem cell adhesion to specific adhesion molecules presented by biomaterials can induce specific differentiation. Mechanical signals can be delivered to stem cells seeded onto biomaterial scaffolds. These approaches would be invaluable for direction of stem cell differentiation and in vivo tissue regeneration using stem cells. PMID:24855545

  19. The effect of blocking angiogenesis on anterior cruciate ligament healing following stem cell transplantation.

    PubMed

    Takayama, Koji; Kawakami, Yohei; Mifune, Yutaka; Matsumoto, Tomoyuki; Tang, Ying; Cummins, James H; Greco, Nick; Kuroda, Ryosuke; Kurosaka, Masahiro; Wang, Bing; Fu, Freddie H; Huard, Johnny

    2015-08-01

    Ruptured human anterior cruciate ligaments (ACL) contain vascular stem cells capable of enhancing the healing of tendon grafts. In the current study we explored the role that neo-angiogenesis plays in ACL healing. ACL-derived CD34+ cells were isolated via Fluorescence Activated Cell Sorting (FACS) from the rupture sites of human ACLs. The cells were then virally transduced to express either vascular endothelial growth factor (VEGF) or soluble FLT-1 (sFLT-1), which is an antagonist of VEGF. We established five groups: CD34+VEGF(100%), where 100% of the cells were transduced with VEGF, CD34+VEGF(25%), where only 25% of the cells were transduced with VEGF, CD34+, CD34+sFLT-1, and a No cells group. The CD34+sFLT1 group had a significant reduction in biomechanical strength compared to the CD34+ group at 4 and 8 weeks; whereas the biomechanical strength of the CD34+VEGF(25%) group was significantly greater than the CD34+ group at week 4; however, no difference was observed by week 8. Immunohistochemical staining demonstrated a significantly lower number of isolectin B4 and hCD31 positive cells, markers associated with angiogenesis, in the CD34+sFLT1 group, and a higher number of isolectin B4 and hCD31 positive cells in the CD34+VEGF(100%) and CD34+VEGF(25%) groups compared to the CD34+ group. Graft maturation was significantly delayed in the CD34+sFLT1 group and accelerated in the CD34+VEGF(25%) group compared to the CD34+ group. In conclusion, blocking VEGF reduced angiogenesis, graft maturation and biomechanical strength following ACL reconstruction. Native expression of VEGF by the CD34+ cells improved tendon graft maturation and biomechanical strength; however, over-expression of VEGF impeded improvements in biomechanical strength. PMID:25965282

  20. Stem-cell therapies for blood diseases

    NASA Astrophysics Data System (ADS)

    Bordignon, Claudio

    2006-06-01

    For decades, transplantation of haematopoietic stem cells - either unmodified, or genetically modified to correct genetic disorders - has been used to treat disorders of the blood and immune systems. The present challenge is to reduce the risk of such transplants and increase the number of patients who can safely access this treatment. In developing countries, such `one-shot' treatments are highly desirable because chronic treatments are difficult to sustain. To make these therapies more accessible and effective it will be important to improve clinical protocols and gene-delivery vectors, and to gain a deeper understanding of stem cells.

  1. Growth-inhibitory effect of neurotrophin-3-secreting adipose tissue-derived mesenchymal stem cells on the D283MED human medulloblastoma cell line

    Microsoft Academic Search

    Young-Hoon Kim; Seung Hee Cho; Soo Jung Lee; Seung Ah Choi; Ji Hoon Phi; Seung-Ki Kim; Kyu-Chang Wang; Byung-Kyu Cho; Chae-Yong Kim

    s  Medulloblastoma (MBL), the most common malignant pediatric brain tumor, is incurable in about one-third of patients and can\\u000a lead to long-term disabilities despite current multimodal treatments. The purpose of this study was to demonstrate in vitro\\u000a biological effects of neurotrophins-3 (NT-3) on MBL cells and to evaluate the growth-inhibitory effect of neurotrophin-3 (NT-3)-secreting\\u000a stem cells on tumor cells. We confirmed

  2. Autologous stem cell transplantation and multiple myeloma cancer stem cells.

    PubMed

    Matsui, William; Borrello, Ivan; Mitsiades, Constantine

    2012-01-01

    It is well established that high-dose therapy (HDT) combined with autologous stem cell transplantation (ASCT) produces superior response rates and progression-free survival compared with conventional chemotherapy in patients with multiple myeloma (MM). Accordingly, MM currently represents the most common indication for ASCT. Despite these clinical improvements, the impact of ASCT on overall survival is unclear because the vast majority of patients eventually experience disease relapse and progression. The continual risk of relapse suggests that malignant cells resistant to HDT possess the clonogenic growth potential to mediate tumor regrowth, and in several diseases cancer stem cells (CSCs) have been identified that are both highly tumorigenic and resistant to standard anticancer approaches. Putative CSCs have been identified in MM, and their characterization may lead to the development of novel maintenance strategies that inhibit the production of new tumor cells, prevent disease relapse, and improve overall survival. PMID:22226109

  3. Collection of hematopoietic stem cells from patients with autoimmune diseases

    Microsoft Academic Search

    RK Burt; A Fassas; JA Snowden; JM van Laar; T Kozak; NM Wulffraat; RA Nash; CE Dunbar; R Arnold; G Prentice; S Bingham; AM Marmont; PA McSweeney

    2001-01-01

    We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis

  4. ECHOCARDIOGRAPHIC EVALUATION OF THE EFFECTS OF STEM CELL THERAPY ON PERFUSION AND FUNCTION IN ISCHEMIC CARDIOMYOPATHY

    PubMed Central

    Inaba, Yoichi; Davidson, Brian P.; Kim, Sajeevani; Liu, Ya Ni; Packwood, William; Belcik, Todd; Xie, Aris; Lindner, Jonathan R.

    2013-01-01

    BACKGROUND Small animal models of ischemic left ventricular (LV) dysfunction are important for the pre-clinical optimization of stem cell therapy. We hypothesized that temporal changes in LV function and regional perfusion after cell therapy can be assessed in mice using echocardiographic imaging. METHODS Wild-type mice (n=25) were studied 7 and 28 days after permanent ligation of the left anterior descending artery. Animals were randomized to receive closed-chest ultrasound-guided intramyocardial delivery of saline (n=13) or 5×105 multipotential adult progenitor cells (MAPC) (n=12) at day 7. Left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volume, left ventricular ejection fraction (LVEF), and stroke volume were measured by high-frequency echocardiography. Multiplanar assessment of perfusion and defect area size were made by myocardial contrast echocardiography (MCE). RESULTS Between day 7 and 28, MAPC-treated animals had a 40–50% reduction in defect size (p<0.001) and a 20–30% increase in total perfusion (p<0.01). Perfusion did not change in non-treated controls. Both LVEDV and LVESV increased between day 7 and 28 in both groups, however LVESV increased to a lesser degree in MAPC-treated versus control mice (+4.2±7.9 vs +19.2±22.0 ?L, p<0.05). LVEF increased in the MAPC-treated mice and decreased in control mice (+3.0±4.3 vs ?5.6±5.9 %, p<0.01). There was a significant linear relation between the change in LVEF and the change in either defect area size or total perfusion. CONCLUSIONS High-frequency echocardiography and MCE in murine models of ischemic LV dysfunction can be used to assess the response to stem cell therapy and to characterize the relationship between spatial flow, ventricular function and ventricular remodeling. PMID:24315764

  5. 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

  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 Properties of Human Dental Pulp Stem Cells

    Microsoft Academic Search

    S. Gronthos; J. Brahim; W. Li; L. W. Fisher; N. Cherman; A. Boyde; P. DenBesten; P. Gehron Robey; S. Shi

    2002-01-01

    In this study, we characterized the self-renewal capability, multi-lineage differentiation capacity, and clonogenic efficiency of human dental pulp stem cells (DPSCs). DPSCs were capable of forming ectopic dentin and associated pulp tissue in vivo. Stromal-like cells were reestablished in culture from primary DPSC transplants and re-transplanted into immunocompromised mice to generate a dentin-pulp-like tissue, demonstrating their self-renewal capability. DPSCs were

  8. LIF promotes neurogenesis and maintains neural precursors in cell populations derived from spiral ganglion stem cells

    Microsoft Academic Search

    Kazuo Oshima; Dawn Tju Wei Teo; Pascal Senn; Veronika Starlinger; Stefan Heller

    2007-01-01

    BACKGROUND: Stem cells with the ability to form clonal floating colonies (spheres) were recently isolated from the neonatal murine spiral ganglion. To further examine the features of inner ear-derived neural stem cells and their derivatives, we investigated the effects of leukemia inhibitory factor (LIF), a neurokine that has been shown to promote self-renewal of other neural stem cells and to

  9. 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

  10. Comparison of Mesenchymal Stem Cell Markers in Multiple Human Adult Stem Cells

    PubMed Central

    Maleki, Masoud; Ghanbarvand, Farideh; Reza Behvarz, Mohammad; Ejtemaei, Mehri; Ghadirkhomi, Elham

    2014-01-01

    Objectives: Mesenchymal stem cells (MSCs) are adult stem cells which identified by adherence to plastic, expression of cell surface markers including CD44, CD90, CD105, CD106, CD166, and Stro-1, lack of the expression of hematopoietic markers, no immunogenic effect and replacement of damaged tissues. These properties led to development of progressive methods to isolation and characterization of MSCs from various sources for therapeutic applications in regenerative medicine. Methods: We isolated MSC-like cells from testis biopsies, ovary, hair follicle and umbilical cord Wharton’s jelly and investigated the expression of specific cell surface antigens using flow cytometry in order to verify stemness properties of these cells. Results: All four cell types adhered to plastic culture flask a few days after primary culture. All our cells positively expressed common MSC- specific cell surface markers. Moreover, our results revealed the expression of CD19and CD45 antigens in these cells. Conclusion: According to our results, high expression of CD44 in spermatogonial stem cells (SSCs), hair follicle stem cells (HFSCs),granulosa cells (GCs)and Wharton’s jelly- MSCs (WJ-MSCs)may help them to maintain stemness properties. Furthermore, we suggest that CD105+SSCs, HFSCs and WJ-MSCs revealed the osteogenic potential of these cells. Moreover, high expression of CD90 in SSCs and HFSCs may associate to higher growth and differentiation potential of these cells. Further, the presence of CD19 on SSCs and GCs may help them to efficiency in response to trans-membrane signals. Thus, these four types of MSCs may be useful in clinical applications and cell therapy. PMID:25473449

  11. Nonmyeloablative Allogeneic Stem Cell Transplantation: Early Promise and Limitations

    Microsoft Academic Search

    NICOLE J. MCCARTHY; MICHAEL R. BISHOP

    Allogeneic stem cell transplantation is used to treat a variety of malignant and nonmalignant hematologic diseases. Conventionally, high-dose chemoradiother- apy-based preparative regimens were considered essen- tial both for tumor eradication and facilitation of donor stem cell engraftment. It is now apparent that an immune-mediated graft-versus-tumor effect has a piv- otal role in the curative potential of allogeneic stem cell transplantation.

  12. Cell Stem Cell Prediction and Testing of Novel Transcriptional

    E-print Network

    Zandstra, Peter W.

    Cell Stem Cell Article Prediction and Testing of Novel Transcriptional Networks Regulating Embryonic Stem Cell Self-Renewal and Commitment Emily Walker,1 Minako Ohishi,1 Ryan E. Davey,1 Wen Zhang,2.stanford@utoronto.ca DOI 10.1016/j.stem.2007.04.002 SUMMARY Stem cell fate is governed by the integration of intrinsic

  13. 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.ac.uk (M.P.), jc4@sanger.ac.uk (J.C.) DOI 10.1016/j.stem.2010.03.004 SUMMARY The transcription factor Oct4 is key in embryonic stem cell identity and reprogramming. Insight into its part- ners should illuminate

  14. 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 Francisco, San Francisco, CA 94158-0725, USA *Correspondence: hannele@u.washington.edu DOI 10.1016/j.stem

  15. Minimal model for stem-cell differentiation.

    PubMed

    Goto, Yusuke; Kaneko, Kunihiko

    2013-09-01

    To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed. PMID:24125305

  16. Hematopoietic Stem Cells and Their Niche

    Microsoft Academic Search

    Hiroko Iwasaki; Toshio Suda

    \\u000a The stem cells’ major capabilities (i.e., the pluripotency and the self-renewal) are the keys to sustain the lifelong functionality\\u000a of the organ. Stem cells reside in the special microenvironment called niche. The niche and stem cells adhere to each other\\u000a via adhesion molecules and exchange the molecular signals that maintain the stem cell features. It has been suggested that\\u000a tumor

  17. The Niche Regulation of Hematopoietic Stem Cells

    Microsoft Academic Search

    Hiroko Iwasaki; Toshio Suda

    \\u000a Stem cells’ major capabilities, that is, pluripotency and self-renewal, are key to sustaining the lifelong functionality of\\u000a organs. Stem cells reside in the special microenvironment called the niche. The niche and stem cells adhere to each other\\u000a via adhesion molecules and exchange the molecular signals that maintain stem cell features. It has been suggested that tumor\\u000a tissue also contains such

  18. Stem cells and tooth tissue engineering

    Microsoft Academic Search

    Amanda H.-H. Yen; Paul T. Sharpe

    2008-01-01

    The notion that teeth contain stem cells is based on the well-known repairing ability of dentin after injury. Dental stem\\u000a cells have been isolated according to their anatomical locations, colony-forming ability, expression of stem cell markers,\\u000a and regeneration of pulp\\/dentin structures in vivo. These dental-derived stem cells are currently under increasing investigation\\u000a as sources for tooth regeneration and repair. Further

  19. Notch signalling in cancer stem cells

    Microsoft Academic Search

    Victoria Bolós; Moisés Blanco; Vanessa Medina; Guadalupe Aparicio; Silvia Díaz-Prado; Enrique Grande

    2009-01-01

    A new theory about the development of solid tumours is emerging from the idea that solid tumours, like normal adult tissues,\\u000a contain stem cells (called cancer stem cells) and arise from them. Genetic mutations encoding for proteins involved in critical\\u000a signalling pathways for stem cells such as BMP, Notch, Hedgehog and Wnt would allow stem cells to undergo uncontrolled proliferation

  20. Stem Cell Research Policies around the World

    PubMed Central

    Dhar, Deepali; Hsi-en Ho, John

    2009-01-01

    The proliferation of stem cell research, conflated with its ethical and moral implications, has led governments to attempt regulation of both the science and funding of stem cells. Due to a diversity of opinions and cultural viewpoints, no single policy or set of rules exist to govern stem cell research. Instead, each country has developed its own policy. The following map catalogs the general legal and political milleu regarding stem cell research by country. PMID:19774124

  1. Epidermal Stem Cells and Their Epigenetic Regulation

    PubMed Central

    Shen, Qi; Jin, Hongchuan; Wang, Xian

    2013-01-01

    Stem cells play an essential role in embryonic development, cell differentiation and tissue regeneration. Tissue homeostasis in adults is maintained by adult stem cells resident in the niches of different tissues. As one kind of adult stem cell, epidermal stem cells have the potential to generate diversified types of progeny cells in the skin. Although its biology is still largely unclarified, epidermal stem cells are widely used in stem cell research and regenerative medicine given its easy accessibility and pluripotency. Despite the same genome, cells within an organism have different fates due to the epigenetic regulation of gene expression. In this review, we will briefly discuss the current understanding of epigenetic modulation in epidermal stem cells. PMID:23999591

  2. College Students’ Conceptions of Stem Cells, Stem Cell Research, and Cloning

    Microsoft Academic Search

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

    2010-01-01

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

  3. Stem Cell Rev . Author manuscript Human bone marrow mesenchymal stem cells: a systematic reappraisal

    E-print Network

    Paris-Sud XI, Université de

    Stem Cell Rev . Author manuscript Page /1 11 Human bone marrow mesenchymal stem cells: a systematic (acronym for Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench Mesenchymal Stem Cell (MSC) biological properties and repair capacity. Part of Genostem activity has been

  4. Stem Cell Reports Quality Metrics for Stem Cell-Derived Cardiac Myocytes

    E-print Network

    Stem Cell Reports Article Quality Metrics for Stem Cell-Derived Cardiac Myocytes Sean P. Sheehy,1, provided the original author and source are credited. SUMMARY Advances in stem cell manufacturing methods have made it possible to produce stem cell-derived cardiac myocytes at industrial scales for in vitro

  5. Summary of current research interests Field of Research: Retinal Stem Cell Biology, Development of Stem Cell

    E-print Network

    Saunders, Mark

    Summary of current research interests Field of Research: Retinal Stem Cell Biology, Development of Stem Cell Based Therapies to treat Retinal Diseases, Endogenous Regeneration of the human Retina Stem is to investigate the application of Müller stem cells in cell replacement therapies for glaucomatous degeneration

  6. Second autologous stem cell transplant: an effective therapy for relapsed multiple myeloma.

    PubMed

    Singh Abbi, Kamal Kant; Zheng, Junting; Devlin, Sean M; Giralt, Sergio; Landau, Heather

    2015-03-01

    Therapeutic options for patients with multiple myeloma (MM) whose disease has relapsed after a prior autologous stem cell transplant (ASCT) include an expanding armamentarium of novel agents, often combined with traditional chemotherapy, or a second ASCT, with no clear standard of care. We retrospectively analyzed the outcomes of 75 patients who underwent salvage melphalan-based ASCT for relapsed MM at Memorial Sloan-Kettering Cancer Center between 1995 and 2012. Conditioning was performed with melphalan 200 mg/m(2) (n = 43), 180 mg/m(2) (n = 1), 140 mg/m(2) (n = 22), and 100 mg/m(2) (n = 9). The median age at second ASCT was 59 years (range, 36 to 75), and 58% (n = 35) were men. Of those with available data, 19% had high-risk cytogenetics (including t (4;14), p53 loss, or del 13q by karyotype) at the time of second ASCT. Median interval between first and salvage ASCT was 37.5 months (range, 6.9 to 111.4). Of 72 assessable patients, 57% had chemotherapy-sensitive disease before to salvage ASCT and 43% were chemoresistant. Four patients died within 100 days of ASCT. Response was assessed at 2 to 3 months post-ASCT, and of 71 assessable patients, 82% achieved at least a partial response, 15% had stable disease, and 3% progressed despite salvage ASCT. After salvage ASCT, 38 patients received maintenance therapy and 14 went on to allogeneic ASCT. The median progression-free survival (PFS) after second autograft was 10.1 months (95% confidence interval [CI], 7.6 to 13.4) and median overall survival (OS) 22.7 months (95% CI, 19.2 to 41.2). Patients with chemosensitive relapse had a trend toward better PFS (hazard ratio [HR], .60 [95% CI, .36 to 1.02]; P = .058) and significantly longer OS (HR, .49 [95% CI, .27 to .88]; P = .017) than patients with resistant relapse. Those with high-risk cytogenetics at the time of second ASCT had higher risk of death (HR, 2.98 [95% CI, 1.28 to 6.97]; P = .012) compared with patients with standard-risk cytogenetics. Salvage ASCT is an effective strategy for relapsed MM with chemosensitive disease and results in comparable PFS and OS to other salvage strategies. PMID:25529381

  7. Stem Cells for Liver Repopulation

    PubMed Central

    Soto-Gutierrez, Alejandro; Navarro-Alvarez, Nalu; Yagi, Hiroshi; Yarmush, Martin L.

    2013-01-01

    Purpose of review The capacity of the liver to regenerate and maintain a constant size despite injury is unique. However, the exact mechanisms are not completely clear. Cell transplantation has been proposed as an alternative treatment of liver diseases. Recent progress has been reported on the generation of stem/progenitor cells that may differentiate towards the hepatic lineage. However, it is currently difficult to determine which of the stem/progenitor cell populations are the best for therapy of a given disease. Recent findings The limited access to donor human hepatocytes has opened a great interest on the generation of hepatocyte-like cells. Several potential cell sources have been identified. However, general standardization of the methods to evaluate these cells is particularly important for the promise of stem/progenitor-derived hepatocyte-based therapies. Moreover, innovations aimed at improving hepatocyte delivery, survival and engraftment have recently opened the field of organ engineering that may improve the perspective of liver repopulation. Summary Here we review current evidence reported from the perspective of potential clinical applications of different hepatic cell sources with repopulation capacities and the future perspectives and tools that can facilitate the translation of laboratory work into clinical success. PMID:19779345

  8. The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells

    SciTech Connect

    Chen, Ying-Chun [Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County 350, Taiwan (China); Hsiao, Jong-Kai; Liu, Hon-Man [Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 106, Taiwan (China); Lai, I-Yin [Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County 350, Taiwan (China); Yao, Ming [Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 106, Taiwan (China); Hsu, Szu-Chun [Department of Laboratory Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 106, Taiwan (China); Ko, Bor-Sheng [Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 106, Taiwan (China); Chen, Yao-Chang [Department of Laboratory Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 106, Taiwan (China); Yang, Chung-Shi [Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County 350, Taiwan (China); Huang, Dong-Ming, E-mail: dmhuang@nhri.org.t [Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County 350, Taiwan (China)

    2010-06-01

    Superparamagnetic iron oxide (SPIO) nanoparticles are very useful for monitoring cell trafficking in vivo and distinguish whether cellular regeneration originated from an exogenous cell source, which is a key issue for developing successful stem cell therapies. However, the impact of SPIO labeling on stem cell behavior remains uncertain. Here, we show the inhibitory effect of Ferucarbotran, an ionic SPIO, on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. Ferucarbotran caused a dose-dependent inhibition of osteogenic differentiation, abolished the differentiation at high concentration, promoted cell migration, and activated the signaling molecules, {beta}-catenin, a cancer/testis antigen, SSX, and matrix metalloproteinase 2 (MMP2). An iron chelator, desferrioxamine, suppressed all the above Ferucarbotran-induced actions, demonstrating an important role of free iron in the inhibition of osteogenic differentiation that is mediated by the promotion of cell mobilization, involving the activation of a specific signaling pathway.

  9. Spermatogonial stem cells: questions, models and perspectives

    Microsoft Academic Search

    Jens Ehmcke; Joachim Wistuba; Stefan Schlatt

    2006-01-01

    This review looks into the phylogeny of spermatogonial stem cells and describes their basic biological features. We are focusing on species-specific differences of spermatogonial stem cell physiology. We propose revised models for the clonal expansion of spermatogonia and for the potential existence of true stem cells and progenitors in primates but not in rodents. We create a new model for

  10. A niche opportunity for stem cell therapeutics

    Microsoft Academic Search

    G B Adams; D T Scadden

    2008-01-01

    The success of hematopoietic stem cell (HSC)-based therapies relies on the ability of the stem cells to both engraft and self-renew sufficiently in the bone marrow microenvironment. Previous studies identified that a number of components of bone contribute to the regulation of HSCs indicating that they participate in a stem cell ‘niche’. This niche is a dynamic microenvironment that changes

  11. Metabolic oxidation regulates embryonic stem cell differentiation

    Microsoft Academic Search

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

    2010-01-01

    Metabolites offer an important unexplored complementary approach to understanding the pluripotency of stem cells. Using MS-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

  12. How Embryonic Stem Cell Lines are Made

    NSDL National Science Digital Library

    Use of embryonic stem cells in research has been hotly debated for several years. This animation presents the basics on how stem cell lines are established. This animation from Cold Spring Harbor Laboratory's Dolan DNA Learning Center presents how embryonic stem cell lines are made through a series of illustrations of the processes involved.

  13. Spontaneous Human Adult Stem Cell Transformation

    Microsoft Academic Search

    Daniel Rubio; Javier Garcia-Castro; Maria C. Martin; Juan C. Cigudosa; Alison C. Lloyd; Antonio Bernad

    2005-01-01

    Human adult stem cells are being evaluated widely for various therapeutic approaches. Several recent clinical trials have reported their safety, showing them to be highly resistant to transformation. The clear similarities between stem cell and cancerstemcellgeneticprogramsarenonethelessthebasisofa recent proposal that some cancer stem cells could derive from humanadultstemcells.Hereweshowthatalthoughtheycanbe managed safely during the standard ex vivo expansion period (6-8 weeks), human mesenchymal

  14. Signaling pathways governing stem-cell fate

    Microsoft Academic Search

    Ulrika Blank; Goran Karlsson; Stefan Karlsson

    2008-01-01

    Hematopoietic stem cells (HSCs) are his- torically the most thoroughly character- ized type of adult stem cell, and the hematopoietic system has served as a principal model structure of stem-cell bi- ology for several decades. However, para- doxically, although HSCs can be defined by function and even purified to near- homogeneity, the intricate molecular ma- chinery and the signaling mechanisms

  15. Epithelial stem cells, wound healing and cancer

    Microsoft Academic Search

    Esther N. Arwert; Esther Hoste; Fiona M. Watt

    2012-01-01

    It is well established that tissue repair depends on stem cells and that chronic wounds predispose to tumour formation. However, the association between stem cells, wound healing and cancer is poorly understood. Lineage tracing has now shown how stem cells are mobilized to repair skin wounds and how they contribute to skin tumour development. The signalling pathways, including WNT and

  16. Stem and Progenitor Cells in the Retina

    Microsoft Academic Search

    Nilanjana Sengupta; Sergio Caballero; Nicanor Moldovan; Maria B. Grant

    2010-01-01

    Regardless of the debate regarding moral issues of using stem cells in research, they are unequivocally useful for understanding pathological angiogenesis, particularly so in the retina. Some important stem cell concepts include a niche, as well as the ideas of self-renewal and plasticity. Self-renewal is the maintenance of a stem cell population, through production of both undifferentiated and further differentiated

  17. Epigenetic regulation of aging stem cells

    Microsoft Academic Search

    E A Pollina; A Brunet

    2011-01-01

    The function of adult tissue-specific stem cells declines with age, which may contribute to the physiological decline in tissue homeostasis and the increased risk of neoplasm during aging. Old stem cells can be ‘rejuvenated’ by environmental stimuli in some cases, raising the possibility that a subset of age-dependent stem cell changes is regulated by reversible mechanisms. Epigenetic regulators are good

  18. Stem cell plasticity revisited: The continuum marrow model and phenotypic changes mediated by microvesicles

    PubMed Central

    Quesenberry, Peter J.; Dooner, Mark S.; Aliotta, Jason M.

    2010-01-01

    The phenotype of marrow hematopoietic stem cells is determined by cell cycle state and microvesicle entry into the stem cells. The stem cell population is continually changing based on cell cycle transit and thus can only be defined on a population basis. Purification of marrow stem cells only addresses the heterogeneity of these populations. When whole marrow is studied, the long-term repopulating stem cells are in active cell cycle. However, with some variability, when highly purified stem cells are studied, the cells appear to be dormant. Thus, the study of purified stem cells is intrinsically misleading. Tissue-derived microvesicles enhanced by injury effect the phenotype of different cell classes. We propose that previously described stem cell plasticity is due to microvesicle modulation. We further propose a stem cell population model in which the individual cell phenotypes continually changes, but the population phenotype is relatively stable. This, in turn, is modulated by microvesicle and microenvironmental influences. PMID:20382199

  19. Mesenchymal stem cells induce dermal fibroblast responses to injury

    SciTech Connect

    Smith, Andria N., E-mail: snosmith@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Willis, Elise, E-mail: elise.willis@gmail.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)] [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Chan, Vincent T. [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)] [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Muffley, Lara A., E-mail: muffley@u.washington.edu.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Isik, F. Frank, E-mail: isik@comcast.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: nicoleg@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: ahocking@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)

    2010-01-01

    Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

  20. Role of the epithelial–mesenchymal transition and its effects on embryonic stem cells

    PubMed Central

    Kim, Ye-Seul; Yi, Bo-Rim; Kim, Nam-Hyung; Choi, Kyung-Chul

    2014-01-01

    The epithelial–mesenchymal transition (EMT) is important for embryonic development and the formation of various tissues or organs. However, EMT dysfunction in normal cells leads to diseases, such as cancer or fibrosis. During the EMT, epithelial cells are converted into more invasive and active mesenchymal cells. E-box-binding proteins, including Snail, ZEB and helix–loop–helix family members, serve as EMT-activating transcription factors. These transcription factors repress the expression of epithelial markers, for example, E-cadherin, rearrange the cytoskeleton and promote the expression of mesenchymal markers, such as vimentin, fibronectin and other EMT-activating transcription factors. Signaling pathways that induce EMT, including transforming growth factor-?, Wnt/glycogen synthase kinase-3?, Notch and receptor tyrosine kinase signaling pathways, interact with each other for the regulation of this process. Although the mechanism(s) underlying EMT in cancer or embryonic development have been identified, the mechanism(s) in embryonic stem cells (ESCs) remain unclear. In this review, we describe the underlying mechanisms of important EMT factors, indicating a precise role for EMT in ESCs, and characterize the relationship between EMT and ESCs. PMID:25081188

  1. Therapeutic stem cells expressing variants of EGFR-specific nanobodies have antitumor effects

    PubMed Central

    van de Water, Jeroen A. J. M.; Bagci-Onder, Tugba; Agarwal, Aayush S.; Wakimoto, Hiroaki; Roovers, Rob C.; Zhu, Yanni; Kasmieh, Randa; Bhere, Deepak; Van Bergen en Henegouwen, Paul M. P.; Shah, Khalid

    2012-01-01

    The deregulation of the epidermal growth factor receptor (EGFR) has a significant role in the progression of tumors. Despite the development of a number of EGFR-targeting agents that can arrest tumor growth, their success in the clinic is limited in several tumor types, particularly in the highly malignant glioblastoma multiforme (GBM). In this study, we generated and characterized EGFR-specific nanobodies (ENb) and imageable and proapoptotic ENb immunoconjugates released from stem cells (SC) to ultimately develop a unique EGFR-targeted therapy for GBM. We show that ENbs released from SCs specifically localize to tumors, inhibit EGFR signaling resulting in reduced GBM growth and invasiveness in vitro and in vivo in both established and primary GBM cell lines. We also show that ENb primes GBM cells for proapoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Furthermore, SC-delivered immunoconjugates of ENb and TRAIL target a wide spectrum of GBM cell types with varying degrees of TRAIL resistance and significantly reduce GBM growth and invasion in both established and primary invasive GBM in mice. This study demonstrates the efficacy of SC-based EGFR targeted therapy in GBMs and provides a unique approach with clinical implications. PMID:23012408

  2. Methods for Stem Cell Production and Therapy

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

  3. Hematopoietic Stem Cell Gene Therapy

    Microsoft Academic Search

    David W. Emery; Tamon Nishino; Ken Murata; Michalis Fragkos; George Stamatoyannopoulos

    2002-01-01

    Gene therapy applications that target hematopoietic stem cells (HSCs) offer great potential for the treatment of hematologic\\u000a disease. Despite this promise, clinical success has been limited by poor rates of gene transfer, poor engraftment of modified\\u000a cells, and poor levels of gene expression. We describe here the basic approach used for HSC gene therapy, briefly review some\\u000a of the seminal

  4. Stem cells: science, policy, and ethics

    PubMed Central

    Fischbach, Gerald D.; Fischbach, Ruth L.

    2004-01-01

    Human embryonic stem cells offer the promise of a new regenerative medicine in which damaged adult cells can be replaced with new cells. Research is needed to determine the most viable stem cell lines and reliable ways to promote the differentiation of pluripotent stem cells into specific cell types (neurons, muscle cells, etc.). To create new cell lines, it is necessary to destroy preimplantation blastocysts. This has led to an intense debate that threatens to limit embryonic stem cell research. The profound ethical issues raised call for informed, dispassionate debate. PMID:15545983

  5. Stem cells: science, policy, and ethics.

    PubMed

    Fischbach, Gerald D; Fischbach, Ruth L

    2004-11-01

    Human embryonic stem cells offer the promise of a new regenerative medicine in which damaged adult cells can be replaced with new cells. Research is needed to determine the most viable stem cell lines and reliable ways to promote the differentiation of pluripotent stem cells into specific cell types (neurons, muscle cells, etc). To create new cell lines, it is necessary to destroy preimplantation blastocysts. This has led to an intense debate that threatens to limit embryonic stem cell research. The profound ethical issues raised call for informed, dispassionate debate. PMID:15545983

  6. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    SciTech Connect

    Nicolay, Nils H., E-mail: n.nicolay@dkfz.de [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Sommer, Eva; Lopez, Ramon; Wirkner, Ute [Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Trinh, Thuy [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Sisombath, Sonevisay [Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Ho, Anthony D.; Saffrich, Rainer [Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg (Germany); Huber, Peter E. [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany)

    2013-12-01

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression.

  7. Muscle stem cells at a glance

    PubMed Central

    Wang, Yu Xin; Dumont, Nicolas A.; Rudnicki, Michael A.

    2014-01-01

    ABSTRACT Muscle stem cells facilitate the long-term regenerative capacity of skeletal muscle. This self-renewing population of satellite cells has only recently been defined through genetic and transplantation experiments. Although muscle stem cells remain in a dormant quiescent state in uninjured muscle, they are poised to activate and produce committed progeny. Unlike committed myogenic progenitor cells, the self-renewal capacity gives muscle stem cells the ability to engraft as satellite cells and capitulate long-term regeneration. Similar to other adult stem cells, understanding the molecular regulation of muscle stem cells has significant implications towards the development of pharmacological or cell-based therapies for muscle disorders. This Cell Science at a Glance article and accompanying poster will review satellite cell characteristics and therapeutic potential, and provide an overview of the muscle stem cell hallmarks: quiescence, self-renewal and commitment. PMID:25300792

  8. Effect of human umbilical cord blood derived lineage negative stem cells transplanted in amyloid-? induced cognitive impaired mice.

    PubMed

    Banik, Avijit; Prabhakar, Sudesh; Kalra, Jasvinder; Anand, Akshay

    2015-09-15

    Alzheimer's disease (AD) is pathologically characterized by extracellular deposition of insoluble amyloid-? (A?) plaques and intracellular tangles made up of phosphorylated tau in brain. Several therapeutic approaches are being carried out in animal AD models for testing their safety and efficacy in altering disease pathology and behavioral deficits. Very few studies have examined the effect of human umbilical cord blood (hUCB) derived stem cells in degenerative disease models despite growing number of cord blood banks worldwide. Here we have examined the therapeutic efficacy of hUCB derived lineage negative (Lin -ve) stem cells in alleviating behavioral and neuropathological deficits in a mouse model of cognitive impairment induced by bilateral intrahippocampal injection of A?-42. Lin -ve cells were transplanted at two doses (50,000 and 100,000) at the site of injury and examined at 10 and 60 days post transplantation for rescue of memory deficits. These cells were found to ameliorate cognitive impairment in 50,000-60 days and 100,000-10 days groups whereas, 50,000-10 days and 100,000-60 days groups could not exert any significant improvement. Further, mice showing spatial memory improvement were mediated by up-regulation of BDNF, CREB and also by concomitant down regulation of Fas-L in their brain. The transplanted cells were found in the host tissue and survived up to 60 days without expressing markers of neuronal differentiation or reducing A? burden in mouse brain. We suggest that these undifferentiated cells could exert neuroprotective effects either through inhibiting apoptosis and/or trophic effects in the brain. PMID:25989508

  9. Complexity of cancer stem cells.

    PubMed

    Sugihara, Eiji; Saya, Hideyuki

    2013-03-15

    Heterogeneity of tumor tissue has been accounted for in recent years by a hierarchy-based model in which cancer stem cells (CSCs) have the ability both to self-renew and to give rise to differentiated tumor cells and are responsible for the overall organization of a tumor. Research into CSCs has progressed rapidly and concomitantly with recent advances in the biology of normal tissue stem cells, resulting in the identification of CSCs in a wide range of human tumors. Studies of mouse models of human cancer have provided further insight into the characteristics of CSCs as well as a basis for the development of novel therapies targeted to these cells. However, recent studies have revealed complexities, such as plasticity of stem cell properties and clonal diversity of CSCs, in certain tumor types that have led to revision of the original CSC model. In this review, we summarize the history of the discovery and characterization of CSCs, as well as address recent advances that have revealed the complexity of these cells and their therapeutic implications. PMID:23180591

  10. Effect of angiotensin II on proliferation and differentiation of mouse induced pluripotent stem cells into mesodermal progenitor cells

    SciTech Connect

    Ishizuka, Toshiaki, E-mail: tishizu@ndmc.ac.jp [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan)] [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan); Goshima, Hazuki; Ozawa, Ayako; Watanabe, Yasuhiro [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan)] [Department of Pharmacology, National Defense Medical College, Tokorozawa, Saitama 359-8513 (Japan)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Treatment with angiotensin II enhanced LIF-induced DNA synthesis of mouse iPS cells. Black-Right-Pointing-Pointer Angiotensin II may enhance the DNA synthesis via induction of superoxide. Black-Right-Pointing-Pointer Treatment with angiotensin II significantly increased JAK/STAT3 phosphorylation. Black-Right-Pointing-Pointer Angiotensin II enhanced differentiation into mesodermal progenitor cells. Black-Right-Pointing-Pointer Angiotensin II may enhance the differentiation via activation of p38 MAPK. -- Abstract: Previous studies suggest that angiotensin receptor stimulation may enhance not only proliferation but also differentiation of undifferentiated stem/progenitor cells. Therefore, in the present study, we determined the involvement of the angiotensin receptor in the proliferation and differentiation of mouse induced pluripotent stem (iPS) cells. Stimulation with angiotensin II (Ang II) significantly increased DNA synthesis in mouse iPS cells cultured in a medium with leukemia inhibitory factor (LIF). Pretreatment of the cells with either candesartan (a selective Ang II type 1 receptor [AT{sub 1}R] antagonist) or Tempol (a cell-permeable superoxide scavenger) significantly inhibited Ang II-induced DNA synthesis. Treatment with Ang II significantly increased JAK/STAT3 phosphorylation. Pretreatment with candesartan significantly inhibited Ang II- induced JAK/STAT3 phosphorylation. In contrast, induction of mouse iPS cell differentiation into Flk-1-positive mesodermal progenitor cells was performed in type IV collagen (Col IV)- coated dishes in a differentiation medium without LIF. When Col IV-exposed iPS cells were treated with Ang II for 5 days, the expression of Flk-1 was significantly increased compared with that in the cells treated with the vehicle alone. Pretreatment of the cells with both candesartan and SB203580 (a p38 MAPK inhibitor) significantly inhibited the Ang II- induced increase in Flk-1 expression. Treatment with Ang II enhanced the phosphorylation of p38 MAPK in Col IV- exposed iPS cells. These results suggest that the stimulation of mouse iPS cells with AT{sub 1}R may enhance LIF-induced DNA synthesis, by augmenting the generation of superoxide and activating JAK/STAT3, and that AT{sub 1}R stimulation may enhance Col IV-induced differentiation into mesodermal progenitor cells via p38 MAPK activation.

  11. Oleuropein enhances osteoblastogenesis and inhibits adipogenesis: the effect on differentiation in stem cells derived from bone marrow

    Microsoft Academic Search

    R. Santiago-Mora; A. Casado-Díaz; M. D. De Castro; J. M. Quesada-Gómez

    2011-01-01

    Summary  The effects of oleuropein on the processes of osteoblastogenesis and adipogenesis in mesenchymal stem cells (MSCs) from human\\u000a bone marrow have been studied. We report that oleuropein, a polyphenol abundant in olive tree products, reduces the expression\\u000a of peroxisome proliferator-activated receptor gamma (PPAR?), inhibits adipocyte differentiation, and enhances differentiation\\u000a into osteoblast.\\u000a \\u000a \\u000a \\u000a \\u000a Introduction  Age-related bone loss is associated with osteoblast insufficiency during

  12. Effects of Naringin on Proliferation and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells In Vitro and In Vivo

    PubMed Central

    Yin, Lihua; Cheng, Wenxiao; Qin, Zishun; Yu, Hongdou; Yu, Zhanhai; Zhong, Mei; Sun, Kemo; Zhang, Wei

    2015-01-01

    This study is to explore the osteogenesis potential of the human periodontal ligament stem cells (hPDLSCs) induced by naringin in vitro and in vitro. The results confirmed that 1??M naringin performs the best effect and a collection of bone-related genes (RUNX2, COL1A2, OPN, and OCN) had significantly higher expression levels compared to the control group. Furthermore, a typical trabecular structure was observed in vivo, surrounded by a large amount of osteoblasts. These results demonstrated that naringin, at a concentration of 1??M, can efficiently promote the proliferation and differentiation of hPDLSCs both in vitro and in vivo.

  13. Effects of novel hydroxyapatite-based 3D biomaterials on proliferation and osteoblastic differentiation of mesenchymal stem cells.

    PubMed

    Karadzic, Ivana; Vucic, Vesna; Jokanovic, Vukoman; Debeljak-Martacic, Jasmina; Markovic, Dejan; Petrovic, Snjezana; Glibetic, Marija

    2015-01-01

    The aim of this study was to examine the differential capacity of isolated dental pulp stem cells (SHED) cultured onto four different scaffold materials. The differential potential of isolated SHED was examined on the following scaffolds: porous hydroxyapatite (pHAP) alone or combined with three polymers [polylactic-co-glycolic acid (PLGA), alginate, and ethylene vinylacetate / ethylene vinylversatate (EVA/EVV)]. SHED were isolated by "outgrowth" method and characterized by the flow cytometry. Viability of cells grown with scaffolds was assessed by MTT and LDH assays. No significant cytotoxic effect of any of the tested materials was shown. Staining with alizarin red and estimated alkaline phosphatase activity to identify differentiation, demonstrated osteoblastic phenotype of SHED and newly deposited and mineralized extra cellular matrix (ECM) in presence of all tested scaffolds. The developed ECM seen at scanning electronic micrographs additionally confirmed the osteogenic differentiation and biocompatibility between cells and materials. In summary, all studied biomaterials are suitable carriers for proliferation and osteoblastic differentiation of dental pulp mesenchymal stem cells in vitro. PMID:24665062

  14. Effect of bisphenol A on pluripotency of mouse embryonic stem cells and differentiation capacity in mouse embryoid bodies.

    PubMed

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

    2013-12-01

    Bisphenol A (BPA) poses potential risks to reproduction and development. However, the mechanism of BPA's effects on early embryonic development is still unknown. Embryonic stem cells (ESC) and embryoid bodies (EB) provide valuable in vitro models for testing the toxic effects of environmental chemicals in early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to BPA for 24h, and general cytotoxicity and the effect of BPA on pluripotency were then evaluated. Meanwhile, mouse embryoid bodies (mEB) were exposed to BPA up to 6 days and their differentiation capacity was evaluated. In mESC and mEB, we found that BPA up-regulated pluripotency markers (Oct4, Sox2 and Nanog) at mRNA and/or protein levels. Moreover, BPA increased the mRNA levels of endodermal markers (Gata4,Sox17) and mesodermal markers (Sma,Desmin), and reduced the mRNA levels of ectodermal markers (Nestin,Fgf5) in mEB. Furthermore, microRNA(miR)-134, an expression inhibitor of pluripotency markers including Oct4, Sox2 and Nanog, was decreased both in BPA-treated mESC and mEB. These results firstly indicate that BPA may disturb pluripotency in mESC and differentiation of mEB, and may inhibit ectodermal lineage differentiation of mEB while miR-134 may play a key role underlying this effect. PMID:24090592

  15. Tumoricidal bystander effect in the suicide gene therapy using mesenchymal stem cells does not injure normal brain tissues.

    PubMed

    Amano, Shinji; Gu, Chunyu; Koizumi, Shinichiro; Tokuyama, Tsutomu; Namba, Hiroki

    2011-07-01

    In our previous rat study, an established intracranial C6 glioma was successfully treated using intratumoral injection of mesenchymal stem cells transduced with the herpes simplex virus-thymidine kinase gene (MSCtk) and systemic administration of ganciclovir (GCV). In the present study, effect of the "bystander effect" associated with the MSCtk/GCV strategy on the background normal brain tissues was examined in both in vitro and in vivo conditions. Rat MSCtk and C6 glioma cells were mixed and seeded on the rat primary neuron and glia co-culture in the medium containing GCV to generate the bystander effect and the numbers of background cells were counted on day 0, 2 and 7. Though the number of MSCtk and C6 cells decreased rapidly due to the bystander effect, most of the neurons and glias survived on day 7. Next, rats were intracranially injected with the MSCtk and C6 cells and then intraperitoneally administered with GCV for 7days. No remarkable histological abnormality including apoptosis was observed in the background brain tissues near the injection site. The present study has demonstrated that the tumoricidal bystander effect does not injure the background normal brain tissue significantly and that the suicide gene therapies are sufficiently safe. PMID:21450400

  16. Generation of Trophoblast Stem Cells from Rabbit Embryonic Stem Cells with BMP4

    Microsoft Academic Search

    Tao Tan; Xianghui Tang; Jing Zhang; Yuyu Niu; Hongwei Chen; Bin Li; Qiang Wei; Weizhi Ji; Anton Wutz

    2011-01-01

    Trophoblast stem (TS) cells are ideal models to investigate trophectoderm differentiation and placental development. Herein, we describe the derivation of rabbit trophoblast stem cells from embryonic stem (ES) cells. Rabbit ES cells generated in our laboratory were induced to differentiate in the presence of BMP4 and TS-like cell colonies were isolated and expanded. These cells expressed the molecular markers of

  17. Endometrial stem cells in regenerative medicine.

    PubMed

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

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo. PMID:25097665

  18. Hematopoietic Stem Cells for Myocardial Regeneration

    Microsoft Academic Search

    Donald Orlic; Richard O. Cannon III

    Adult bone marrow consists of several populations of stem cells that are the focus of investigations into their potential\\u000a to regenerate nonhematopoietic tissues. According to this hypothesis, bone marrow stem cells display a plasticity not previously\\u000a recognized. Although data supporting bone marrow stem cell plasticity is extensive, many researchers dispute this concept.\\u000a One of the most controversial aspects of stem

  19. Stem Cell Chronicles: Autobiographies Within Genomes

    Microsoft Academic Search

    Darryl Shibata; Simon Tavaré

    2007-01-01

    Human stem cell studies are difficult because many of the powerful experimental approaches that mark and follow stem cells\\u000a and their progeny are impractical. Moreover, humans are long-lived, and it would literally take a lifetime to follow stem\\u000a cell fates prospectively. Considering these hurdles, an ideal method would not require prior experimental manipulations but\\u000a still allow “observations” of human stem

  20. Adult stem cells in the endometrium.

    PubMed

    Gargett, Caroline E; Masuda, Hirotaka

    2010-11-01

    Rare cells with adult stem cell activity were recently discovered in human endometrium. Endometrial stem/progenitor cell candidates include epithelial, mesenchymal and endothelial cells, and all may contribute to the rapid endometrial regeneration following menstruation, rather than a single candidate. Endometrial mesenchymal stem-like cells (eMSC) are prospectively isolated as CD146(+)PDGF-R?(+) cells and are found in both basalis and functionalis as perivascular cells. Epithelial progenitor cells are detected in colony forming unit assays but their identity awaits elucidation. They are postulated to reside in the basalis in gland bases. Endometrial stem/progenitor cells may be derived from endogenous stem cells, but emerging evidence suggests a bone marrow contribution. Endometrial endothelial progenitor cells are detected as side population cells, which express several endothelial cell markers and differentiate into endometrial glandular epithelial, stromal and endothelial cells. Investigating endometrial stem cell biology is crucial to understanding normal endometrial physiology and to determine their roles in endometrial proliferative diseases. The nature of endometriosis suggests that initiation of ectopic endometrial lesions involves endometrial stem/progenitor cells, a notion compatible with Sampson's retrograde menstruation theory and supported by the demonstration of eMSC in menstrual blood. Evidence of cancer stem cells (CSC) in endometrial cancer indicates that new avenues for developing therapeutic options targeting CSC may become available. We provide an overview of the accumulating evidence for endometrial stem/progenitor cells and their possible roles in endometrial proliferative disorders, and discuss the unresolved issues. PMID:20627991

  1. Saving Superman: Ethics and Stem Cell Research

    NSDL National Science Digital Library

    Doug M. Post

    2006-01-01

    This case explores the political and ethical issues associated with stem cell research. Students read the case describing Christopher Reeve’s accident and injuries and his advocacy for stem cell research along with background readings on stem cells and the ethics of stem cell research. They are then assigned to one of four stakeholder groups and asked to develop a position on whether or not the U.S. Senate should expand stem cell research with a focus on the ethics underlying the issue.  They present their positions in class in a simulated public hearing.

  2. The Therapeutic Effects of Optimal Dose of Mesenchymal Stem Cells in a Murine Model of an Elastase Induced-Emphysema

    PubMed Central

    Kim, You-Sun; Kim, Ji-Young; Huh, Jin Won; Lee, Sei Won; Choi, Soo Jin

    2015-01-01

    Background Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only 5×104 MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.

  3. Neural stem cell engineering: directed differentiation of adult and embryonic stem cells into neurons Matthew J. Robertson1

    E-print Network

    Schaffer, David V.

    Neural stem cell engineering: directed differentiation of adult and embryonic stem cells. Adult neural stem cells and neurogenesis 3.1. Hippocampal stem cells 3.2. Subventricular zone (SVZ) and olfactory bulb stem cells 3.3. Progenitors derived from non-neurogenic regions 3.4. Adult neural stem cell

  4. Osteogenic Differentiation of Rat Mesenchymal Stem Cells from Adipose Tissue in Comparison with Bone Marrow Mesenchymal Stem Cells: Melatonin As a Differentiation Factor

    Microsoft Academic Search

    Arash Zaminy; Iraj Ragerdi Kashani; Mohammad Barbarestani; Azim Hedayatpour

    2008-01-01

    Background: Adipose-derived stem cells (ADSC) could be an appealing alternative to bone marrow stem cells (BMSC) for engineering cell-based osteoinductive grafts. Meanwhile, prior studies have demonstrated that melatonin can stimulate osteogenic differentiation. Therefore, we assayed and compared the melatonin effect on osteogenic differentiation of BMSC with that of ADSC. Methods: Mesenchymal stem cells (MSC) were isolated from the bone marrow

  5. Effects of hypoxia on proliferation and osteogenic differentiation of periodontal ligament stem cells: an in vitro and in vivo study.

    PubMed

    Zhang, Q B; Zhang, Z Q; Fang, S L; Liu, Y R; Jiang, G; Li, K F

    2014-01-01

    Changes in oxygen concentration may influence various innate characteristics of stem cells. The effects of varying oxygen concentration on human periodontal ligament stem cells (HPDLSCs) has not been explored, particularly under hypoxia-related conditions. First, HPDLSCs were cultured from the periodontium of human teeth using the outgrowth method. STRO-1 and CD146 expression of HPDLSCs was investigated by flow cytometry. To detect the multilineage differentiation capacities of HPDLSCs, osteogenic-like and adipogenic-like states were induced in cells. Next, HPDLSCs (passage 3) were exposed to normal oxygen (21% O2) or hypoxia (2% O2) conditions for 7 days and cell proliferation was evaluated. After culture in osteogenic medium for 7 days, osteoblastic differentiation was evaluated by semi-quantitative reverse transcription-polymerase chain reaction analysis to detect 3 osteoblastic markers: core-binding factor a 1/runt-related transcription factor 2, osteocalcin, and osteopontin. In addition, each cell group was incubated with a hydroxyapatite/tricalcium phosphate carrier and transplanted subcutaneously into the back of immunocompromised mice to investigate transplantation differences in vivo. HPDLSCs were isolated, cultured, and successfully identified. After exposure of HPDLSCs to hypoxia for 7 days, the proliferation rate was increased and showed higher osteogenic differentiation potential compared to control cells. After 12 weeks of transplantation, hypoxia-treated HPDLSCs differentiated into osteoblast-like cells that formed bone-like structures. These results suggest that oxygen concentrations affect various aspects of HPDLSC physiology and that hypoxia enhances osteogenic differentiation both in vivo and in vitro. Oxygen concentration may be a critical parameter for HPDLSCs during expansion and differentiation. PMID:25501232

  6. Stem cell factor and granulocyte colony-stimulating factor exhibit therapeutic effects in a mouse model of CADASIL.

    PubMed

    Liu, Xiao-Yun; Gonzalez-Toledo, Maria E; Fagan, Austin; Duan, Wei-Ming; Liu, Yanying; Zhang, Siyuan; Li, Bin; Piao, Chun-Shu; Nelson, Lila; Zhao, Li-Ru

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a Notch3 dominant mutation-induced cerebral small vascular disease, is characterized by progressive degeneration of vascular smooth muscle cells (vSMCs) of small arteries in the brain, leading to recurrent ischemic stroke, vascular dementia and death. To date, no treatment can stop or delay the progression of this disease. Herein, we determined the therapeutic effects of stem cell factor (SCF) in combination with granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) in a mouse model of CADASIL carrying the human mutant Notch3 gene. SCF+G-CSF was subcutaneously administered for 5 days and repeated 4 times with 1-4 month intervals. We found through water maze testing that SCF+G-CSF treatment improved cognitive function. SCF+G-CSF also attenuated vSMC degeneration in small arteries, increased cerebral blood vascular density, and inhibited apoptosis in CADASIL mice. We also discovered that loss of cerebral capillary endothelial cells and neural stem cells/neural progenitor cells (NSCs/NPCs) occurred in CADASIL mice. SCF+G-CSF treatment inhibited the CADASIL-induced cell loss in the endothelia and NSCs/NPCs and promoted neurogenesis. In an in vitro model of apoptosis, SCF+G-CSF prevented apoptotic cell death in vSMCs through AKT signaling and by inhibiting caspase-3 activity. These data suggest that SCF+G-CSF restricts the pathological progression of CADASIL. This study offers new insights into developing therapeutic strategies for CADASIL. PMID:25251607

  7. Stem cells news update: a personal perspective.

    PubMed

    Wong, Sc

    2013-12-01

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

  8. Understanding cancer stem cell heterogeneity and plasticity

    Microsoft Academic Search

    Dean G Tang

    2012-01-01

    Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity.

  9. New insights into liver stem cells

    Microsoft Academic Search

    E. Gaudio; G. Carpino; V. Cardinale; A. Franchitto; P. Onori; D. Alvaro

    2009-01-01

    Hepatic progenitor cells are bi-potential stem cells residing in human and animal livers that are able to differentiate towards the hepatocytic and the cholangiocytic lineages. In adult livers, hepatic progenitor cells are quiescent stem cells with a low proliferating rate, representing a reserve compartment that is activated only when the mature epithelial cells of the liver are continuously damaged or

  10. Mesenchymal stem cells in health and disease

    Microsoft Academic Search

    Lorenzo Moretta; Vito Pistoia; Antonio Uccelli

    2008-01-01

    Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells that can be isolated from many adult tissues. They can differentiate into cells of the mesodermal lineage, such as adipocytes, osteocytes and chondrocytes, as well as cells of other embryonic lineages. MSCs can interact with cells of both the innate and adaptive immune systems, leading to the modulation

  11. Cancer Stem Cells: Lessons From Melanoma

    Microsoft Academic Search

    Caterina La Porta

    2009-01-01

    The model of cancer stem cells in tumor development states that tumors contain a subset of cells that both self renew and\\u000a give rise to differentiated progeny. Like normal adult tissue stem cells, cancer stem cells are a minority of the whole tumor\\u000a and are the only cells that are able to maintain tumor growth indefinitely. In the present review

  12. Pluripotent stem cells and their niches

    Microsoft Academic Search

    M. William Lensch; Laurence Daheron; Thorsten M. Schlaeger

    2006-01-01

    The ability of stem cells to self-renew and to replace mature cells is fundamental to ontogeny and tissue regeneration. Stem\\u000a cells of the adult organism can be categorized as mono-, bi-, or multipotent, based on the number of mature cell types to\\u000a which they can give rise. In contrast, pluripotent stem cells of the early embryo have the ability to

  13. Therapeutic Potential of Stem Cells in Diabetes

    Microsoft Academic Search

    E. Roche; R. Enseńat-Waser; J. A. Reig; J. Jones; T. León-Quinto; B. Soria

    Stem cells possess the ability to self-renew by symmetric divisions and, under certain circumstances, differentiate to a committed\\u000a lineage by asymmetric cell divisions. Depending on the origin, stem cells are classified as either embryonic or adult. Embryonic\\u000a stem cells are obtained from the inner cell mass of the blastocyst, a structure that appears during embryonic development\\u000a at day 6 in

  14. Appropriate nonwoven filters effectively capture human peripheral blood cells and mesenchymal stem cells, which show enhanced production of growth factors.

    PubMed

    Hori, Hideo; Iwamoto, Ushio; Niimi, Gen; Shinzato, Masanori; Hiki, Yoshiyuki; Tokushima, Yasuo; Kawaguchi, Kazunori; Ohashi, Atsushi; Nakai, Shigeru; Yasutake, Mikitomo; Kitaguchi, Nobuya

    2015-03-01

    Scaffolds, growth factors, and cells are three essential components in regenerative medicine. Nonwoven filters, which capture cells, provide a scaffold that localizes and concentrates cells near injured tissues. Further, the cells captured on the filters are expected to serve as a local supply of growth factors. In this study, we investigated the growth factors produced by cells captured on nonwoven filters. Nonwoven filters made of polyethylene terephthalate (PET), biodegradable polylactic acid (PLA), or chitin (1.2-22 ?m fiber diameter) were cut out as 13 mm disks and placed into cell-capturing devices. Human mesenchymal stem cells derived from adipose tissues (h-ASCs) and peripheral blood cells (h-PBCs) were captured on the filter and cultured to evaluate growth factor production. The cell-capture rates strongly depended on the fiber diameter and the number of filter disks. Nonwoven filter disks were composed of PET or PLA fibers with fiber diameters of 1.2-1.8 ?m captured over 70% of leukocytes or 90% of h-ASCs added. The production of vascular endothelial growth factor (VEGF), transforming growth factor ?1, and platelet-derived growth factor AB were significantly enhanced by the h-PBCs captured on PET or PLA filters. h-ASCs on PLA filters showed significantly enhanced production of VEGF. These enhancements varied with the combination of the nonwoven filter and cells. Because of the enhanced growth factor production, the proliferation of human fibroblasts increased in conditioned medium from h-PBCs on PET filters. This device consisting of nonwoven filters and cells should be investigated further for possible use in the regeneration of impaired tissues. PMID:25322703

  15. Effect of Calcium Sprays on Mechanical Strength and Cell Wall Fractions of Herbaceous Peony (Paeonia Lactiflora Pall.) Inflorescence Stems

    PubMed Central

    Li, Chengzhong; Tao, Jun; Zhao, Daqiu; You, Chao; Ge, Jintao

    2012-01-01

    Calcium is an essential element and imparts significant structural rigidity to the plant cell walls, which provide the main mechanical support to the entire plant. In order to increase the mechanical strength of the inflorescence stems of herbaceous peony, the stems are treated with calcium chloride. The results shows that preharvest sprays with 4% (w/v) calcium chloride three times after bud emergence are the best at strengthening “Da Fugui” peonies’ stems. Calcium sprays increased the concentrations of endogenous calcium, total pectin content as well as cell wall fractions in herbaceous peonies stems, and significantly increased the contents of them in the top segment. Correlation analysis showed that the breaking force of the top segment of peonies’ stems was positively correlated with the ratio of water insoluble pectin to water soluble pectin (R = 0.673) as well as lignin contents (R = 0.926) after calcium applications. PMID:22606005

  16. Contribution of Stem Cells to Kidney Repair

    Microsoft Academic Search

    Benedetta Bussolati; Peter Viktor Hauser; Raquel Carvalhosa; Giovanni Camussi

    2009-01-01

    A current explanation for development of chronic renal injury is the imbalance between injurious mechanism and regenerative repair. The possibility that stem cells contribute to the repair of glomerular and tubular damage is of great interest for basic and translational research. Endogenous bone marrow-derived stem cells have been implicated in the repair of renal tissue, although the lineage of stem

  17. Effect of cold storage and cryopreservation of immature non-human primate testicular tissue on spermatogonial stem cell potential in xenografts

    Microsoft Academic Search

    Kirsi Jahnukainen; Jens Ehmcke; Scott D. Hergenrother; Stefan Schlatt

    2007-01-01

    BACKGROUND: Successful cryopreservation of gonadal tissue is an important factor in guaranteeing the fertility preservation via germ cell or testicular tissue transplantation. The aim of this study was to evaluate the effects of cooling and cryopreservation on spermatogonial stem cell survival and function of immature non-human primate testicular tissue xenografted to nude mice. METHODS: Group 1 (control group) received subcutaneous

  18. Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

    Microsoft Academic Search

    Kasper W. ter Horst

    2010-01-01

    The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by the acute inflammatory response on one hand and by scar formation on the

  19. The "skinny" on Wnt signaling in stem cells.

    PubMed

    Morgan, Bruce A

    2013-12-01

    Although previous reports suggested that canonical Wnt signaling has opposing effects on epidermal and hair follicle stem cells, two recent papers (Choi et al., 2013; Lim et al., 2013) now show that Wnt signaling promotes proliferation in both stem cell populations, revealing new insights into regeneration of both skin compartments. PMID:24315435

  20. The skeletal muscle satellite cell: stem cell or son of stem cell?

    Microsoft Academic Search

    Peter S. Zammit; Jonathan R. Beauchamp

    2001-01-01

    The concept of the adult tissue stem cell is fundamental to models of persistent renewal in functionally post-mitotic tissues. Although relatively ignored by stem cell biology, skeletal muscle is a prime example of an adult tissue that can generate terminally differentiated cells uniquely specialized to carry out tissue-specific functions. This capacity is attributed to satellite cells, a population of undifferentiated,