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1

The immunosuppressive effect of embryonic stem cells and mesenchymal stem cells on both primary and secondary alloimmune responses  

Microsoft Academic Search

Recently, both embryonic stem cells and mesenchymal stem cells have been demonstrated to have immunosuppressive effects. The purpose of this study was to elucidate whether the embryonic stem cells and\\/or mesenchymal stem cells modulate both primary and secondary alloimmune responses. Both stem cells suppressed in vitro proliferation and cytokine production in primary alloimmune responses. They also suppressed in vitro proliferation

Kyu Hyun Han; Hee Gyung Kang; Hae Jin Gil; Eun Mi Lee; Curie Ahn; Jaeseok Yang

2010-01-01

2

Effects of Simulated Microgravity on Embryonic Stem Cells  

Microsoft Academic Search

There have been many studies on the biological effects of simulated microgravity (SMG) on differentiated cells or adult stem cells. However, there has been no systematic study on the effects of SMG on embryonic stem (ES) cells. In this study, we investigated various effects (including cell proliferation, cell cycle distribution, cell differentiation, cell adhesion, apoptosis, genomic integrity and DNA damage

Yulan Wang; Lili An; Yuanda Jiang; Haiying Hang

2011-01-01

3

Cardiac cell therapy: boosting mesenchymal stem cells effects.  

PubMed

Acute myocardial infarction is a major problem of world public health and available treatments have limited efficacy. Cardiac cell therapy is a new therapeutic strategy focused on regeneration and repair of the injured cardiac muscle. Among different cell types used, mesenchymal stem cells (MSC) have been widely tested in preclinical studies and several clinical trials have evaluated their clinical efficacy in myocardial infarction. However, the beneficial effects of MSC in humans are limited due to poor engraftment and survival of these cells, therefore ways to overcome these obstacles should improve efficacy. Different strategies have been used, such as genetically modifying MSC, or preconditioning the cells with factors that potentiate their survival and therapeutic mechanisms. In this review we compile the most relevant approaches used to improve MSC therapeutic capacity and to understand the molecular mechanisms involved in MSC mediated cardiac repair. PMID:22350458

Samper, E; Diez-Juan, A; Montero, J A; Sepúlveda, P

2013-06-01

4

Effects of Simulated Microgravity on Embryonic Stem Cells  

PubMed Central

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

Jiang, Yuanda; Hang, Haiying

2011-01-01

5

Mesenchymal stem cell effects on T-cell effector pathways  

PubMed Central

Mesenchymal stem (stromal) cells (MSCs) are rare, multipotent progenitor cells that can be isolated and expanded from bone marrow and other tissues. Strikingly, MSCs modulate the functions of immune cells, including T cells, B cells, natural killer cells, monocyte/macrophages, dendritic cells, and neutrophils. T cells, activated to perform a range of different effector functions, are the primary mediators of many autoimmune and inflammatory diseases as well as of transplant rejection and graft-versus-host disease. Well-defined T-cell effector phenotypes include the CD4+ (T helper cell) subsets Th1, Th2, and Th17 cells and cytotoxic T lymphocytes derived from antigen-specific activation of naďve CD8+ precursors. In addition, naturally occurring and induced regulatory T cells (Treg) represent CD4+ and CD8+ T-cell phenotypes that potently suppress effector T cells to prevent autoimmunity, maintain self-tolerance, and limit inflammatory tissue injury. Many immune-mediated diseases entail an imbalance between Treg and effector T cells of one or more phenotypes. MSCs broadly suppress T-cell activation and proliferation in vitro via a plethora of soluble and cell contact-dependent mediators. These mediators may act directly upon T cells or indirectly via modulation of antigen-presenting cells and other accessory cells. MSC administration has also been shown to be variably associated with beneficial effects in autoimmune and transplant models as well as in several human clinical trials. In a small number of studies, however, MSC administration has been found to aggravate T cell-mediated tissue injury. The multiple effects of MSCs on cellular immunity may reflect their diverse influences on the different T-cell effector subpopulations and their capacity to specifically protect or induce Treg populations. In this review, we focus on findings from the recent literature in which specific modulatory effects of MSCs on one or more individual effector T-cell subsets and Treg phenotypes have been examined in vitro, in relevant animal models of in vivo immunological disease, and in human subjects. We conclude that MSCs have the potential to directly or indirectly inhibit disease-associated Th1, Th2, and Th17 cells as well as cytotoxic T lymphocytes but that many key questions regarding the potency, specificity, mechanistic basis, and predictable therapeutic value of these modulatory effects remain unanswered.

2011-01-01

6

Immunomodulatory Effect of Mesenchymal Stem Cells on B Cells  

PubMed Central

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

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

2012-01-01

7

Mesenchymal stem cell effects on T-cell effector pathways  

Microsoft Academic Search

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

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

2011-01-01

8

Side effects of retroviral gene transfer into hematopoietic stem cells  

Microsoft Academic Search

Recent conceptual and technical improve- ments have resulted in clinically meaning- ful levels of gene transfer into repopulat- ing hematopoietic stem cells. At the same time, evidence is accumulating that gene therapy may induce several kinds of unex- pected side effects, based on preclinical and clinical data. To assess the therapeu- tic potential of genetic interventions in hematopoietic cells, it

Christopher Baum; Jochen Dullmann; Zhixiong Li; Boris Fehse; Johann Meyer; David A. Williams; Christof von Kalle

2003-01-01

9

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

Microsoft Academic Search

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

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

2008-01-01

10

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

PubMed Central

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

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

2010-01-01

11

The effects of aging on stem cell behavior in Drosophila  

Microsoft Academic Search

Throughout life, adult stem cells play essential roles in maintaining tissue and organ function by providing a reservoir of cells for homeostasis and regeneration. A decline in stem cell number or activity may, therefore, lead to compromised organ and tissue function that is characteristic of aging. Drosophila has emerged as an ideal system for studying the relationship between stem cells

Lei Wang; D. Leanne Jones

2011-01-01

12

Effects of benzene inhalation on murine pluripotent stem cells  

Microsoft Academic Search

Effects of benzene inhalation on mouse pluripotent hematopoietic stem cells have been evaluated. Male mice 8–12 wk old were exposed to 400 ppm benzene for 6 h\\/d, 5 d\\/wk, for up to 9˝ wk. A t various time intervals exposed and control animals were killed, and cardiac blood was evaluated for changes in white blood cell (WBC) and red blood

E. P. Cronkite; T. Inoue; A. L. Carsten; M. E. Miller; J. E. Bullis; R. T. Drew

1982-01-01

13

Stem cell differentiation and the effects of deficiency  

Microsoft Academic Search

Stem cells have several unique attributes, the key features being their potency and plasticity. They have the ability to give rise to multiple cell lineages and to transdifferentiate into totally different cell type(s) when relocated to a novel stem cell niche. Most self-renewing tissues are served by stem cells. At the ocular surface, the corneo-scleral limbus is believed to provide

H S Dua; A Joseph; V A Shanmuganathan; R E Jones

2003-01-01

14

Effective elimination of cancer stem cells by magnetic hyperthermia.  

PubMed

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

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

2013-03-12

15

Mesenchymal Stem Cell Mechanobiology  

Microsoft Academic Search

Bone marrow-derived multipotent stem and stromal cells (MSCs) are likely candidates for cell-based therapies for various conditions\\u000a including skeletal disease. Advancement of these therapies will rely on an ability to identify, isolate, manipulate, and deliver\\u000a stem cells in a safe and effective manner. Although it is clear that physical signals affect tissue morphogenesis, stem cell\\u000a differentiation, and healing processes, integration

Alesha B. Castillo; Christopher R. Jacobs

2010-01-01

16

Effects of bleomycin on mouse bone-marrow stem cells.  

PubMed

The mouse hematopoietic stem-cell population was tested by the spleen colony technique for effects of the antineoplastic agent bleomycin (BLM). The time response of normal bone marrow was investigated by a single dose of BLM (400 mg/kg) between 0 and 72 hours. The dose response was studied over a wide range of doses (from 40 to 1,600 mg/kg) at a 4-hour exposure. Additional experiments concerned 1) the fraction of colony-forming units in the S phase after BLM administration (by means of pulse hydroxyurea treatment), 2) the response of bone marrow stimulated by endotoxin, and 3) the effects of split-dose treatments. The relatively low toxicity of BLM on both the differentiated and stem-cell populations of unstimulated bone marrow was confirmed and detailed. This drug exhibited peculiar, proliferation-dependent cell inactivation kinetics. Furthermore, BLM induced parasynchronous behavior in the unstimulated stem-cell population. The various aspects of BLM action are discussed with regard to its use in cancer chemotherapy. PMID:51084

Briganti, G; Galloni, L; Levi, G; Spalletta, V; Mauro, F

1975-07-01

17

Effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma  

Microsoft Academic Search

The purpose of this study was to determine the effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. We performed a retrospective review of 67 patients newly diagnosed with multiple myeloma at Mayo Clinic and treated with a single regimen prior to stem cell transplantation between January of 2000 and September of 2001. Stem cells

I M Ghobrial; A Dispenzieri; K L Bundy; D A Gastineau; S V Rajkumar; T M Therneau; M Q Lacy; T E Witzig; M R Litzow; B R Christensen; S Hayman; C G Pribula; M A Gertz

2003-01-01

18

Radiation-Induced Bystander Effects in Cultured Human Stem Cells  

PubMed Central

Background The radiation-induced “bystander effect” (RIBE) was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR). RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC) are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed. Methodology/Principal Findings Human bone-marrow mesenchymal stem cells (hMSC) and embryonic stem cells (hESC) were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05). A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05). Conclusions/Significance These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.

Sokolov, Mykyta V.; Neumann, Ronald D.

2010-01-01

19

Stem Cells  

Microsoft Academic Search

\\u000a To fully understand the biological meaning of the term stem cell (SC) it is useful to clarify the derivation of the root staminal, even though modern research published in English-speaking journals never seem to use the term staminal. While there are\\u000a no doubts that the term SC originated in the context of two major embryological questions, the continuity of the

Manuela Monti; Carlo Alberto Redi

20

Immunotherapy following hematopoietic stem cell transplantation: potential for synergistic effects  

PubMed Central

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

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

2011-01-01

21

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

NASA Astrophysics Data System (ADS)

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

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

2009-06-01

22

Laser biomodulation on stem cells  

NASA Astrophysics Data System (ADS)

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.

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

2001-08-01

23

Trafficking of stem cells.  

PubMed

Stem cells undergo regulated trafficking from the developmental stages to the adulthood. Stem cell migration is critical to organize developing organs and likely contributes postnatally to tissue regeneration. Here, we review the molecular mechanisms underlying migration of hematopoietic stem cells, neural stem cells, and primordial germ cells, revealing common operative pathways. PMID:21618080

Magnon, Claire; Lucas, Daniel; Frenette, Paul S

2011-01-01

24

The Effects of Anticholinergic Insecticides on Human Mesenchymal Stem Cells  

Microsoft Academic Search

Mesenchymal stem cells (MSCs) are located primarily in the bone marrow and are characterized by their capacity to differen- tiate into mesenchymal lineages such as bone, fat, and cartilage in response to appropriate signals. Several signaling mechanisms act to control MSC survival, proliferation, and differentiation, and failure or disruption of these signaling pathways can lead to degenerative disease or neoplasia.

Martin J. Hoogduijn; Zoltan Rakonczay; Paul G. Genever

2006-01-01

25

Stem Cells and Cancer  

Microsoft Academic Search

Proteins from the Polycomb group (PcG) are epigenetic chromatin modifiers involved in cancer development and also in the maintenance of embryonic and adult stem cells. The therapeutic potential of stem cells and the growing conviction that tumors contain stem cells highlights the importance of understanding the extrinsic and intrinsic circuitry controlling stem cell fate and their connections to cancer.

Merel E. Valk-Lingbeek; Sophia W. M. Bruggeman; Maarten van Lohuizen

2004-01-01

26

Toward ‘SMART’ stem cells  

Microsoft Academic Search

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

T Cheng

2008-01-01

27

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

PubMed

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

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

2013-01-14

28

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

Microsoft Academic Search

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

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

2006-01-01

29

Aging Effect on Neurotrophic Activity of Human Mesenchymal Stem Cells  

PubMed Central

Clinical efficacy of stem cells for nerve repair is likely to be influenced by issues including donor age and in vitro expansion time. We isolated human mesenchymal stem cells (MSC) from bone marrow of young (16–18 years) and old (67–75 years) donors and analyzed their capacity to differentiate and promote neurite outgrowth from dorsal root ganglia (DRG) neurons. Treatment of MSC with growth factors (forskolin, basic fibroblast growth factor, platelet derived growth factor-AA and glial growth factor-2) induced protein expression of the glial cell marker S100 in cultures from young but not old donors. MSC expressed various neurotrophic factor mRNA transcripts. Growth factor treatment enhanced the levels of BDNF and VEGF transcripts with corresponding increases in protein release in both donor cell groups. MSC in co-culture with DRG neurons significantly enhanced total neurite length which, in the case of young but not old donors, was further potentiated by treatment of the MSC with the growth factors. Stem cells from young donors maintained their proliferation rate over a time course of 9 weeks whereas those from the old donors showed increased population doubling times. MSC from young donors, differentiated with growth factors after long-term culture, maintained their ability to enhance neurite outgrowth of DRG. Therefore, MSC isolated from young donors are likely to be a favourable cell source for nerve repair.

Brohlin, Maria; Kingham, Paul J.; Novikova, Liudmila N.; Novikov, Lev N.; Wiberg, Mikael

2012-01-01

30

Excessive T cell depletion of peripheral blood stem cells has an adverse effect upon outcome following allogeneic stem cell transplantation  

Microsoft Academic Search

We evaluated the outcome of two modes of T cell depletion for HLA-identical sibling stem cell transplants in 34 consecutive adult patients: group A (n = 11) received PBSC post CliniMACs immuno-magnetic enrichment of CD34+ cells and group B (n = 23) received bone marrow following in vitro incubation with CAMPATH-1M and complement. All patients received an identical conditioning regimen

R Chakraverty; S Robinson; K Peggs; PD Kottaridis; MJ Watts; SJ Ings; G Hale; H Waldmann; DC Linch; AH Goldstone; S Mackinnon

2001-01-01

31

Brain tumor stem cells  

Microsoft Academic Search

The concept of brain tumor stem cells is gaining increased recognition in neuro-oncology. Until recently, the paradigm of\\u000a a tumor-initiating stem cell was confined to hematopoietic malignancies where the hierarchical lineages of stem progenitor\\u000a cells are well established. The demonstration of persistent stem cells and cycling progenitors in the adult brain, coupled\\u000a with the expansion of the cancer stem cell

Georgia Panagiotakos; Viviane Tabar

2007-01-01

32

Umbilical Cord Stem Cells  

Microsoft Academic Search

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

Kathy E. Mitchell

33

Stem cell culture engineering  

Microsoft Academic Search

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

Gargi Seth; Catherine M. Verfaillie

2005-01-01

34

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

PubMed

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

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

2012-10-17

35

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

Microsoft Academic Search

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

Ying Liang; Gary Van Zant; Stephen J. Szilvassy

2005-01-01

36

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

SciTech Connect

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.

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

37

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

PubMed Central

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

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

2012-01-01

38

Hematopoietic Stem Cells and Somatic Stem Cells  

Microsoft Academic Search

\\u000a Stem cells are unspecialized cells that can differentiate to generate more specialized cell types responsible for tissue-specific\\u000a function. During development, the differentiation of pluripotent embryonic stem cells leads to the production of specialized\\u000a somatic cells that are ultimately responsible for the structure and function of all adult tissues and organs. “Naturally”\\u000a pluripotent cells exist only at the earliest stages of

Kah Yong Tan; Francis S. Kim; Amy J. Wagers; Shane R. Mayack

39

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

NASA Astrophysics Data System (ADS)

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

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

2013-03-01

40

Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines  

PubMed Central

Background Many cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized. Methods Cell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20–80 ?M curcumin for 30 hrs. Cell lines surviving 40 or 60 ?M curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-?B were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 ?M curcumin to determine whether their sensitivity was different from the original lines. Results The cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 ?M curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-?B and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity to curcumin when compared with the original lines. Conclusion Our results suggest that curcumin not only eliminates cancer cells but also targets CSCs. Therefore, curcumin may be an effective compound for treating esophageal and possibly other cancers in which CSCs can cause tumor recurrence.

2012-01-01

41

Plerixafor is effective and safe for stem cell mobilization in heavily pretreated germ cell tumor patients  

Microsoft Academic Search

Up to 10% of germ cell tumor patients require salvage high-dose chemotherapy with stem cell support, achieving cure rates in the range of 10–60%. Stem cell mobilization may be difficult in these patients because of multiple lines of treatment known to seriously hamper stem cell recovery. Plerixafor significantly enhances the success of the CD34+ cell harvest, even in cases where

S Kobold; J Isernhagen; K Hübel; N Kilic; C Bogner; N Frickhofen; C Bokemeyer; W Fiedler

2011-01-01

42

Targeting Leukemic Stem Cells  

Microsoft Academic Search

The stem cell concept and asymmetric cell division are best understood in the hematopoietic system. Hematopoietic malignancies\\u000a resemble many of the known normal mature hematopoietic lineages that originate from stem cells. Leukemias in particular, were\\u000a shown to arise from leukemic stem cells. General characteristics of stem cells such as self-renewal, self-protection and proliferative\\u000a quiescence clearly point toward the need for

Angelika M. Burger

43

Neuroprotective effect of mesenchymal and neural stem and progenitor cells on sensorimotor recovery after brain injury.  

PubMed

We studied the effect of systemic administration of multipotent stem cells on impaired neurological status in rats with brain injury. It was found that transplantation of multipotent mesenchymal stromal cells of the bone marrow or human neural stem and progenitor cells to rats with local brain injury promoted recovery of the brain control over locomotor function and proprioceptive sensitivity of forelegs. The dynamics of neurological recovery was similar after transplantation of fetal neural stem and progenitor cells and multipotent mesenchymal stromal cells. Transplantation of cell cultures improved survival of experimental animals. It should be noted that administration of neural stem and progenitor cells prevented animal death not only in the acute traumatic period, but also in delayed periods. PMID:22977876

Poltavtseva, R A; Silachev, D N; Pavlovich, S V; Kesova, M I; Yarygin, K N; Lupatov, A Yu; Van'ko, L V; Shuvalova, M P; Sukhikh, G T

2012-08-01

44

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

NASA Astrophysics Data System (ADS)

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

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

2010-04-01

45

Stem Cells in Prostate.  

National Technical Information Service (NTIS)

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

G. Risbridger

2004-01-01

46

Regenerative Effects of Transplanted Mesenchymal Stem Cells in Fracture Healing  

PubMed Central

Mesenchymal stem cells (MSC) have a therapeutic potential in patients with fractures to reduce the time of healing and treat non-unions. The use of MSC to treat fractures is attractive as it would be implementing a reparative process that should be in place but occurs to be defective or protracted and MSC effects would be needed only for the repairing time that is relatively brief. However, an integrated approach to define the multiple regenerative contributions of MSC to the fracture repair process is necessary before clinical trials are initiated. In this study, using a stabilized tibia fracture mouse model, we determined the dynamic migration of transplanted MSC to the fracture site, their contributions to the repair process initiation and their role in modulating the injury-related inflammatory responses. Using MSC expressing luciferase, we determined by bioluminescence imaging that the MSC migration at the fracture site is time- and dose-dependent and, it is exclusively CXCR4-dependent. MSC improved the fracture healing affecting the callus biomechanical properties and such improvement correlated with an increase in cartilage and bone content, and changes in callus morphology as determined by micro-computed-tomography and histological studies. Transplanting CMV-Cre-R26R-LacZ-MSC, we found that MSC engrafted within the callus endosteal niche. Using MSC from BMP-2-Lac-Z mice genetically modified using a bacterial artificial chromosome system to be ?-gal reporters for BMP-2 expression, we found that MSC contributed to the callus initiation by expressing BMP-2. The knowledge of the multiple MSC regenerative abilities in fracture healing will allow to design novel MSC-based therapies to treat fractures.

Granero-Molto, Froilan; Weis, Jared A.; Miga, Michael I.; Landis, Benjamin; Myers, Timothy J.; O'Rear, Lynda; Longobardi, Lara; Jansen, E. Duco; Mortlock, Douglas P.; Spagnoli, Anna

2012-01-01

47

Mitochondria in stem cells  

PubMed Central

The current status of knowledge about mitochondrial properties in mouse, monkey and human embryonic, adult and precursor stem cells is discussed. Topics include mitochondrial localization patterns, oxygen consumption and ATP content in cells as they relate to the maintenance of stem cell properties and subsequent differentiation of stem cells into specific cell types. The significance of the perinuclear arrangement of mitochondria, which may be a characteristic feature of stem cells, as well as the expression of mitochondrial DNA regulatory proteins and mutations in the mitochondrial stem cell genome is also discussed.

Lonergan, Thomas; Bavister, Barry; Brenner, Carol

2011-01-01

48

Effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma.  

PubMed

The purpose of this study was to determine the effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. We performed a retrospective review of 67 patients newly diagnosed with multiple myeloma at Mayo Clinic and treated with a single regimen prior to stem cell transplantation between January of 2000 and September of 2001. Stem cells were collected from 24 patients who received thalidomide, 200 mg/day, with dexamethasone as initial therapy before stem cell collection. These patients were compared with 43 control patients seen during the same period who had received only one previous regimen before stem cell collection and transplantation. The cumulative thalidomide dose before stem cell collection was 17 000 mg over a median of four cycles (range, 2-7 cycles). The thalidomide and control groups were not significantly different in their baseline characteristics, number of stem cells collected, time to collection, or time to engraftment of neutrophils or platelet count of 50 000/microl. Time to platelet count of 20 000/microl was delayed by a median of 4 days (P=0.008), but platelet transfusion requirements did not differ (P=0.95). We concluded that thalidomide does not substantially affect peripheral cell mobilization or engraftment. PMID:12953131

Ghobrial, I M; Dispenzieri, A; Bundy, K L; Gastineau, D A; Rajkumar, S V; Therneau, T M; Lacy, M Q; Witzig, T E; Litzow, M R; Christensen, B R; Hayman, S; Pribula, C G; Gertz, M A

2003-09-01

49

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

Microsoft Academic Search

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

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

2001-01-01

50

Stemming the Stem Cell Setback  

Microsoft Academic Search

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

Patrick J. Fleis

2003-01-01

51

Cancer stem cells - normal stem cells \\  

Microsoft Academic Search

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

Mariusz Z. Ratajczak

2005-01-01

52

Oncogenic effects of miR-10b in glioblastoma stem cells.  

PubMed

MicroRNAs and cancer stem cells have emerged as critical players in glioblastoma, one of the deadliest human cancers. In this study, we investigated the expression and function of microRNA-10b in glioblastoma cells and stem cells. An analysis of The Cancer Genome Atlas data revealed a correlation between high miR-10b levels and poor prognosis in glioblastoma patients. We measured the levels of miR-10b and found that it is upregulated in human glioblastoma tissues, glioblastoma cell and stem cell lines as compared to normal human tissues or astrocytes. Inhibition of miR-10b with a specific antagomir inhibited the proliferation of glioblastoma established and stem cell lines. Inhibition of miR-10b strongly reduced cell invasion and migration in glioblastoma cell and stem cell lines while overexpression of miR-10b induced cell migration and invasion. We also investigated several predicted targets of miR-10b but could not verify any of them experimentally. Additionally, miR-10b inhibition significantly decreased the in vivo growth of stem cell-derived orthotopic GBM xenografts. Altogether, our findings confirm the oncogenic effects of miR-10b in GBM cells and show for the first time a role of this microRNA in GBM stem cells. Targeting miR-10b might therefore inhibit glioblastoma stem cells, which are thought to be at the origin of glioblastoma and to contribute its recurrence and resistance to therapy. PMID:23307328

Guessous, Fadila; Alvarado-Velez, Melissa; Marcinkiewicz, Lukasz; Zhang, Ying; Kim, Jungeun; Heister, Simon; Kefas, Benjamin; Godlewski, Jakub; Schiff, David; Purow, Benjamin; Abounader, Roger

2013-01-10

53

Human Embryonic Stem Cells  

Microsoft Academic Search

Human embryonic stem cells hold great promise in furthering our treatment of disease and increasing our understanding of early development. This chapter describes protocols for the derivation and maintenance of human embryonic stem cells. In addition, it summarizes briefly several alternative methods for the culture of human embryonic stem cells. Thus, this chapter provides a good starting point for researchers

Hidenori Akutsu; Chad A. Cowan; Douglas Melton

2006-01-01

54

Stem Cell Biology  

Microsoft Academic Search

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

Elizabeth O. Hexner; Stephen G. Emerson

55

Targeting cancer stem cells for more effective therapies: Taking out cancer's locomotive engine.  

PubMed

Novel therapies for the treatment of solid tumors have generally failed to improve patient overall survival. These therapeutic approaches are typically focused on targeting signaling pathways implicated in cell growth and/or survival in order to shrink the malignant mass and achieve an objective clinical response; however, too often these responses are followed by eventual regrowth of the tumor. This clinical conundrum could be explained by the existence of a tumorigenic cell population that is relatively resistant to these therapies and retains pluripotent status in order to repopulate the original tumor and/or contribute to distant metastasis following treatment. Compelling data from liquid tumors, and more recently from studies focused on solid tumors, now support the existence of such tumorigenic cells (i.e., cancer stem cells) as a distinct subpopulation within the total tumor cell mass. These cancer stem cells (CSCs), as compared to the non-CSC population, have the ability to reconstitute the primary tumor phenotype when transplanted into recipient animals. In addition, data are beginning to emerge demonstrating that many standard-of-care chemotherapeutics are less effective in promoting cell death or cytostasis in these putative cancer stem cells as compared to effects in the non-stem cell cancerous cells. Therefore, targeting these locomotive drivers of tumors, the cancer stem cell population, should be considered a high priority in the continued pursuit of more effective cancer therapies. PMID:19539800

Winquist, Raymond J; Boucher, Diane M; Wood, Mark; Furey, Brinley F

2009-04-01

56

Artificial Stem Cell Niches  

PubMed Central

Stem cells are characterized by their dual ability to reproduce themselves (self-renew) and specialize (differentiate), yielding a plethora of daughter cells that maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells retain their unique functions only if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such “artificial niches” constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration.

Lutolf, Matthias P.; Blau, Helen M.

2011-01-01

57

Stemming vision loss with stem cells  

PubMed Central

Dramatic advances in the field of stem cell research have raised the possibility of using these cells to treat a variety of diseases. The eye is an excellent target organ for such cell-based therapeutics due to its ready accessibility, the prevalence of vasculo- and neurodegenerative diseases affecting vision, and the availability of animal models to demonstrate proof of concept. In fact, stem cell therapies have already been applied to the treatment of disease affecting the ocular surface, leading to preservation of vision. Diseases in the back of the eye, such as macular degeneration, diabetic retinopathy, and inherited retinal degenerations, present greater challenges, but rapidly emerging stem cell technologies hold the promise of autologous grafts to stabilize vision loss through cellular replacement or paracrine rescue effects.

Marchetti, Valentina; Krohne, Tim U.; Friedlander, David F.; Friedlander, Martin

2010-01-01

58

Brain Tumor Stem Cells  

Microsoft Academic Search

Cancers are composed of heterogeneous cell popula- tions ranging from highly proliferative immature cells to more dif- ferentiated cells of various cell lineages. Recent advances in stem cell research have allowed for the demonstration of the existence of cancer stem cells in acute myeloid leukemia, breast cancer, and, most recently, in brain tumors. Each of these has some similarities with

ICHIRO NAKANO; HARLEY I. KORNBLUM

2006-01-01

59

Lymphohematopoietic stem cell engraftment.  

PubMed

Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Recent work in murine transplant models, however, indicates that engraftment is determined by the ratio of donor to host stem cells, i.e., stem cell competition. One hundred centigray whole body irradiation is stem cell toxic and nonmyelotoxic, thus allowing for higher donor chimerism in a murine syngeneic transplant setting. This nontoxic stem cell transplantation can be applied to allogeneic transplant with the addition of a tolerizing step; in this case presensitization with donor spleen cells and administration of CD40 ligand antibody to block costimulation. The stem cells that engraft in the nonmyeloablated are in G0, but are rapidly induced (by 12 hours) to enter the S phase after in vivo engraftment. Exposure of murine marrow to cytokines (IL-3, IL-6, IL-11 and steel factor) expands progenitor clones, induces stem cells into cell cycle, and causes a fluctuating engraftment phenotype tied to phase of cell cycle. These data indicate that the concepts of stem cell competition and fluctuation of stem cell phenotype with cell cycle transit should underlie any new stem cell engraftment strategy. PMID:10372109

Quesenberry, P J; Stewart, F M; Zhong, S; Habibian, H; McAuliffe, C; Reilly, J; Carlson, J; Dooner, M; Nilsson, S; Peters, S; Stein, G; Stein, J; Emmons, R; Benoit, B; Bertoncello, I; Becker, P

1999-04-30

60

Effect of BMP-2 from matrices of different stiffnesses for the modulation of stem cell fate.  

PubMed

Stem cells cultured on extracellular matrix (ECM) with different stiffnesses have been shown to engage into different lineage commitments. However, in vivo, the components of the ECM are known to bind and strongly interact with growth factors. The effect, on the stem cell fate, of the cooperation between the mechanical properties and the growth factor in the same microenvironment has not yet been investigated. Here, we propose a protocol for mimicking this stem cell microenvironment with an in vitro system. This system consists in grafting (without using a spacer) biomolecules that contain N-termini groups onto hydrogel (poly(acrylamide-co-acrylic acid)) surfaces of various stiffnesses ranging from 0.5 to 70 kPa. First, we demonstrate that the commitment of mesenchymal stem cell populations changes in response to the substrate's rigidity, with myogenic differentiation occurring at 13-17 kPa and osteogenic differentiation at 45-49 kPa. Chemical grafting of soft and stiff matrices with an osteogenic factor (BMP-2(mimetic peptide)) results only in osteogenic differentiation. Also, when grafted on even softer gels (0.5-3.5 kPa), the BMP-2(mimetic peptide) had no effect on the stem cell differentiation. We prove that correct organization of F-actin cytoskeleton due to the mechanical properties of the microenvironment is necessary for BMP-induced smad1/5/8 phosphorylation and nuclear translocation. These results suggest that stem cell differentiation is dictated mechanically, but in the presence of a biochemical factor, the effect of the mechanical factor on stem cell commitment is modified. This can explain the diversity of stem cell behaviors in vivo where different growth factors are sequestrated on the ECM. PMID:23290467

Zouani, Omar F; Kalisky, Jérôme; Ibarboure, Emmanuel; Durrieu, Marie-Christine

2013-01-03

61

Novel Protective Effects of Stem Cell Factor in a Murine Model of Acute Septic Peritonitis  

Microsoft Academic Search

Mast cells participate in the host response during sepsis and have been shown to have a protective effect in a murine model of acute septic peritonitis and multi-organ failure initiated by cecal ligation and puncture (CLP). Stem cell factor (SCF) is a hematopoi- etic cytokine important in mast cell proliferation and activation. In the present study, we examined the protective

Cynthia L. Bone-Larson; Cory M. Hogaboam; Matthew L. Steinhauser; Sandra H. P. Oliveira; Nicholas W. Lukacs; Robert M. Strieter; Steven L. Kunkel

2000-01-01

62

Neural Stem Cells  

Microsoft Academic Search

This article is concerned with the idea that neural precursor cells in vertebrates can self-renew and give rise to all cell types within the nervous system. Supportive evidence for this notion of neural stem cells comes from clonal analyses undertaken both in vivo and in vitro. Neural stem cells also give rise to other cells in the body, including skin

Mark Murphy; Kate Reid; Renée Dutton; Gordon Brooker; Perry F Bartlett

1997-01-01

63

Comparing the Immunoregulatory Effects of Stem Cells from Human Exfoliated Deciduous Teeth and Bone Marrow-derived Mesenchymal Stem Cells.  

PubMed

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

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

2013-08-28

64

The in vivo effect of chelidonine on the stem cell system of planarians.  

PubMed

The presence of adult pluripotent stem cells and the amazing regenerative capabilities make planarian flatworms an extraordinary experimental model to assess in vivo the effects of substances of both natural and synthetic origin on stem cell dynamics. This study focuses on the effects of chelidonine, an alkaloid obtained from Chelidonium majus. The expression levels of molecular markers specific for stem or differentiated cells were compared in chelidonine-treated and control planarians. The use of these markers demonstrates that chelidonine produces in vivo a significant anti-proliferative effect on planarian stem cells in a dose-dependent fashion. In response to chelidonine treatment mitotic abnormalities were also observed and the number of cells able to proceed to anaphase/telophase appeared significantly reduced with respect to the controls. Our results support the possibility that chelidonine acts on cell cycle progression by inhibition of tubulin polymerization. These studies provide a basis for preclinical evaluation in vivo of the effects of chelidonine on physiologically proliferating stem cells. PMID:22503932

Isolani, Maria Emilia; Pietra, Daniele; Balestrini, Linda; Borghini, Alice; Deri, Paolo; Imbriani, Marcello; Bianucci, Anna Maria; Batistoni, Renata

2012-04-03

65

Stem Cell Transplants  

NSDL National Science Digital Library

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

Slesnick, Irwin

2004-01-01

66

Stem cell plasticity  

Microsoft Academic Search

The stem cell story begins with the recognition of the regenerative powers of the head of the Lernean Hydra and the human\\u000a liver (Prometheus) by the ancient Greeks. In modern times, the adult human stem cell has been epitomized by the hematopoietic\\u000a stem cell in the bone marrow. More recently, bone marrow derived cells were reported to contribute to nonhematopoietic

Alexandros Spyridonidis; Tina Tomann; Robert Zeiser; Marie Follo; Yannis Metaxas; Jürgen Finke

2005-01-01

67

Mesenchymal stem cells  

Microsoft Academic Search

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

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

2005-01-01

68

Embryonic Stem Cells  

Microsoft Academic Search

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

Victoria L. Browning; Jon S. Odorico

69

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

PubMed

This article examines the current use and future implications of stem cell therapy in treating Multiple Sclerosis (MS). MS is the most common neurological disease in young adults, affecting approximately two million people worldwide. Currently there is no cure for MS. The standard treatment of MS involves disease-modifying drugs, which work to alleviate the symptoms of MS. However, these drugs carry adverse side effects and are ineffective in preventing disease progression in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first used in 1995 to treat patients with severe rapidly progressing MS. The HSCT treatment protocol has evolved into a less intense conditioning regimen that is currently demonstrating efficacy in treating patients with variable disease severity-with best results in early-stage rapidly progressing MS patients with active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental stem cell therapy currently undergoing clinical trials. Animal models and early clinical trials have shown promise that MSCT might be a low risk treatment to precipitate neuroregeneration and immunomodulation in MS patients. Specifically, neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial therapeutic approach, holds promise for a better treatment for MS. PMID:23862098

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

2013-06-30

70

Hematopoietic Stem-Cell Transplantation in the Pediatric Population. Executive Summary. Effective Health Care Program. Comparative Effectiveness Review Number 48.  

National Technical Information Service (NTIS)

Hematopoietic stem-cell transplantation (HSCT) refers to a procedure in which hematopoietic progenitor cells, including repopulating stem cells, are infused to restore bone marrow function in patients. HSCT is categorized by the source of the stem cells, ...

2012-01-01

71

Skeletal muscle stem cells  

Microsoft Academic Search

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

Jennifer CJ Chen; David J Goldhamer

2003-01-01

72

Optimizing stem cell culture  

PubMed Central

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

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

2010-01-01

73

Gastric Epithelial Stem Cells  

PubMed Central

Advances in our understanding of stem cells in the gastrointestinal tract include the identification of molecular markers of stem and early progenitor cells in the small intestine. Although gastric epithelial stem cells have been localized, little is known about their molecular biology. Recent reports describe the use of inducible Cre recombinase activity to indelibly label candidate stem cells and their progeny in the distal stomach, (ie, the antrum and pylorus). No such lineage labeling of epithelial stem cells has been reported in the gastric body (corpus). Among stem cells in the alimentary canal, those of the adult corpus are unique in that they lie close to the lumen and increase proliferation following loss of a single mature progeny lineage, the acid-secreting parietal cell. They are also unique in that they neither depend on Wnt signaling nor express the surface marker Lgr5. Because pathogenesis of gastric adenocarcinoma has been associated with abnormal patterns of gastric differentiation and with chronic tissue injury, there has been much research on the response of stomach epithelial stem cells to inflammation. Chronic inflammation, as induced by infection with Helicobacter pylori, affects differentiation and promotes metaplasias. Several studies have identified cellular and molecular mechanisms in spasmolytic polypeptide–expressing (pseudopyloric) metaplasia. Researchers have also begun to identify signaling pathways and events that take place during embryonic development that eventually establish the adult stem cells to maintain the specific features and functions of the stomach mucosa. We review the cytologic, molecular, functional, and developmental properties of gastric epithelial stem cells.

MILLS, JASON C.; SHIVDASANI, RAMESH A.

2013-01-01

74

Skeletal muscle stem cells  

PubMed Central

Satellite cells are myogenic stem cells responsible for the post-natal growth, repair and maintenance of skeletal muscle. This review focuses on the basic biology of the satellite cell with emphasis on its role in muscle repair and parallels between embryonic myogenesis and muscle regeneration. Recent advances have altered the long-standing view of the satellite cell as a committed myogenic stem cell derived directly from the fetal myoblast. The experimental basis for this evolving perspective will be highlighted as will the relationship between the satellite cell and other newly discovered muscle stem cell populations. Finally, advances and prospects for cell-based therapies for muscular dystrophies will be addressed.

Chen, Jennifer CJ; Goldhamer, David J

2003-01-01

75

Engineering stem cell niches in bioreactors  

PubMed Central

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

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

2013-01-01

76

Effects of hyperthermia and radiation on mouse testis stem cells  

SciTech Connect

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

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

1981-11-01

77

Patenting of stem cells.  

PubMed

Investors in any new technology are concerned to protect their investment, a key part of such protection being the availability of patent protection. Stem cells, human embryonic stem cells in particular, are a highly controversial area, and this controversy extends to the patenting of stem cells. In this article, the legal issues affecting patenting of stem cell technology in the USA and Europe are reviewed. The types of patents that have been granted are also considered, as an illustration of the protection that can be obtained. Finally, the overall trends in patent filings are discussed, to identify key aspects of the patent landscape. PMID:17465737

Williams, Gareth

2006-09-01

78

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

SciTech Connect

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

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

2008-09-12

79

Effects of surface molecular chirality on adhesion and differentiation of stem cells.  

PubMed

Chirality is one of the most fascinating and ubiquitous cues in nature, especially in life. The effects of chiral surfaces on stem cells have, however, not yet been revealed. Herein we examined the molecular chirality effect on stem cell behaviors. Self assembly monolayers of l- or d-cysteine (Cys) were formed on a glass surface coated with gold. Mesenchymal stem cells (MSCs) derived from bone marrow of rats exhibited more adhering preference and thus less cell spreading on the l surface than on the d one at the confluent condition. More protein adsorption was observed on the l surface after immersed in cell culture medium with fetal bovine serum. After osteogenic and adipogenic co-induction at the confluent condition, a larger proportion of cells became osteoblasts on the d surface, while the adipogenic fraction on the l surface was found to be higher than on the d surface. In order to interpret how this chirality effect worked, we fabricated Cys microislands of two sizes on the non-fouling poly(ethylene glycol) hydrogel to pre-define the spreading areas of single cells. Then the differentiation extents did not exhibit a significant difference between l and d surfaces under a given area of microislands, yet very significant differences of osteogenesis and adipogenesis were found between different areas. So, the molecular chirality influenced stem cells, probably via favored adsorption of natural proteins on the l surface, which led to more cell adhesion; and the larger cell spreading area with higher cell tension in turn favored osteogenesis rather than adipogenesis. As a result, this study reveals the molecular chirality on material surfaces as an indirect regulator of stem cells. PMID:23981354

Yao, Xiang; Hu, Yiwen; Cao, Bin; Peng, Rong; Ding, Jiandong

2013-08-24

80

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

Microsoft Academic Search

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

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

2010-01-01

81

STEM CELLS, CELL TRANSPLANTATION AND LIVER REPOPULATION  

PubMed Central

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

Oertel, Michael; Shafritz, David A.

2008-01-01

82

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

PubMed

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

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

2012-08-11

83

The role of stem cells in aging  

Microsoft Academic Search

The objectives of this review were first to critically review what is known about the effects of aging on stem cells in general, and hematopoietic stem cells in particular. Secondly, evidence is marshaled in support of the hypothesis that aging stem cells play a critical role in determining the effects of aging on organ function, and ultimately on the lifespan

Gary Van Zant; Ying Liang

2003-01-01

84

Effect of intracerebral transplantation of mesenchymal stem cells on pial microcirculation in rats.  

PubMed

We studied the effect of intracerebral transplantation of bone marrow mesenchymal stem cells on microcirculation (density of microvascular network and reactivity of arterioles) in the pia mater of 2-3-month-old rats. It was found that after transplantation of mesenchymal stem cells, the density of pial microcirculatory network in the contralateral hemisphere significantly increased (by 1.7 times; p<0.05) in comparison with both intact animals and controls. The number of arterioles in the studied area increased most markedly (by ?2.5 times; p<0.05) in comparison with other groups. Intracerebral transplantation of mesenchymal stem cells or conditioned culture medium (?-MEM) had no effect on reactivity of pial arterioles. PMID:23667891

Sokolova, I B; Sergeev, I V; Bilibina, A A; Anisimov, S V; Dvoretsky, D P

2013-05-01

85

Stem Cell Transplantation for Neuroprotection in Stroke  

PubMed Central

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

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

2013-01-01

86

Regional Anatomic and Age Effects on Cell Function of Human Adipose-Derived Stem Cells  

Microsoft Academic Search

Adipose tissue has been shown to contain adult mesenchy- mal stem cells that have therapeutic applications in regenerative med- icine. There is evidence that the ability of adipose precursor cells to grow and differentiate varies among fat depots and changes with age. Defining these variations in cell function and molecular mechanisms of adipogenesis will facilitate the development of cell-based therapies.

Bret M. Schipper; Kacey G. Marra; Wei Zhang; Albert D. Donnenberg; J. Peter Rubin

2008-01-01

87

Stem cells and progenitor cells in renal disease  

Microsoft Academic Search

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

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

2005-01-01

88

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

PubMed

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

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

2013-02-12

89

Bone marrow stem cells.  

PubMed

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

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

2013-01-01

90

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

PubMed

The avidin-biotin system is a highly specific reaction that has been used in a wide range of biomedical applications, including surface modification and cell patterning. We systematically examined a number of avidin derivatives as the basis for a simple and cost effective tissue culture polystyrene substrate surface modification for human stem cell culture. Non-specific adhesion between human mesenchymal stem cells and various avidin derivatives, media conditions, and subsequent biotinylation reactions was quantified. We observed significant non-specific cell adhesion to avidin and strepthavidin, indicating that previous observations using this system may be artifactual. Seeding of cells in serum free media, blocking with bovine serum albumin, and the use of the avidin derivative neutravidin were all necessary for elimination of background adhesion. Neutravidin conjugated with biotinylated bsp-RGD(15) peptide provided the most robust cell adhesion, as well as the greatest increase in cell adhesion over background levels. PMID:23452388

Schmidt, Ray C; Healy, Kevin E

2013-02-27

91

Therapeutic effects of mesenchymal stem cells on renal ischemia-reperfusion injury: a matter of genetic transfer?  

PubMed

Accumulating evidence indicates that the protective effect of mesenchymal stem cells in models of tissue injury is related to the endocrine/pcrine release of factors. The delivery of growth factors, cytokines, prostaglandins, enzymes or extracellular vesicles from mesenchymal stem cells to target cells may induce cell reprogramming and de novo expression of factors involved in tissue proliferation and repair. A recent paper showed that Wharton jelly-derived mesenchymal stem cells interact with injured renal tubular epithelial cells, inducing the expression of native and foreign hepatocyte growth factor necessary for renal repair and fibrogenesis inhibition. The genetic exchange between resident and mesenchymal stem cells, probably mediated through microvesicles, therefore appears instrumental in mesenchymal stem cell therapeutic effects. PMID:23731907

Bruno, Stefania; Bussolati, Benedetta

2013-06-01

92

Therapeutic effects of mesenchymal stem cells on renal ischemia-reperfusion injury: a matter of genetic transfer?  

PubMed Central

Accumulating evidence indicates that the protective effect of mesenchymal stem cells in models of tissue injury is related to the endocrine/pcrine release of factors. The delivery of growth factors, cytokines, prostaglandins, enzymes or extracellular vesicles from mesenchymal stem cells to target cells may induce cell reprogramming and de novo expression of factors involved in tissue proliferation and repair. A recent paper showed that Wharton jelly-derived mesenchymal stem cells interact with injured renal tubular epithelial cells, inducing the expression of native and foreign hepatocyte growth factor necessary for renal repair and fibrogenesis inhibition. The genetic exchange between resident and mesenchymal stem cells, probably mediated through microvesicles, therefore appears instrumental in mesenchymal stem cell therapeutic effects.

2013-01-01

93

Stem cells and genetic disease  

Microsoft Academic Search

Stem cell research is now a very broad field encompassing cells derived from all stages of life from the embryonic stem cells of the early blastocyst through to the adult stem cells of many tissues of the body. Adult stem cells from a variety of tissues are proving to be pluripotent and can differentiate into cell types different from the

A. Mackay-Sim; P. Silburn

2008-01-01

94

Human Embryonic Stem Cells  

Microsoft Academic Search

\\u000a Stem cells can be isolated from a variety of sources and they are ­typically classified based on their tissue of origin. Embryonic\\u000a stem cells are, as the name indicates, derived from the inner cell mass of pre-implantation stage blastocysts at day 5–7 post\\u000a fertilization. These cells possess qualities such as pluripotency and a seemingly limitless capacity to proliferate in vitro

Mikael C. O. Englund; Peter Sartipy; Johan Hyllner

95

Brain Tumor Stem Cells  

Microsoft Academic Search

The dogma that solid tumors are composed of tumor cells that all share the same ability to produce proliferating daughter\\u000a cells has been challenged in recent years. There is growing evidence that many adult tissues contain a set of tissue stem\\u000a cells, which might undergo malignant transformation while retaining their stem cell characteristics. These include the ability\\u000a of indefinite self-renewal

Christian Nern; Daniel Sommerlad; Till Acker; Karl H. Plate

96

Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro  

Microsoft Academic Search

Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s) between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to have

Victoria Brankin; Marcus RP Mitchell; Bob Webb; Morag G Hunter

2003-01-01

97

Peripheral Blood Stem Cells: Transplantation and Beyond  

Microsoft Academic Search

Peripheral blood stem cells are rapidly becoming a major source of hemopoietic stem cells for transplanta- tion in patients with various hematological and oncolog- ical conditions. Clinical results of peripheral blood stem cell transplantation (PBSCT) have shown benefits of earlier hemopoietic recovery, lower morbidity, and greater cost-effectiveness compared with conventional bone marrow transplant. Moreover, the relative ease of obtaining large

ALBERT K. W. LIE; L. BIK TO

98

Substrate Modulus Directs Neural Stem Cell Behavior  

Microsoft Academic Search

Although biochemical signals that modulate stem cell self-renewal and differentiation were extensively studied, only recently were the mechanical properties of a stem cell's microenvironment shown to regulate its behavior. It would be desirable to have independent control over biochemical and mechanical cues, to analyze their relative and combined effects on stem-cell function. We developed a synthetic, interfacial hydrogel culture system,

Krishanu Saha; Albert J. Keung; Elizabeth F. Irwin; Yang Li; Lauren Little; David V. Schaffer; Kevin E. Healy

2008-01-01

99

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

PubMed Central

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

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

2013-01-01

100

Effective electrochemotherapy for proliferation control of adult human mesenchymal stem cells  

Microsoft Academic Search

Clinically chemo-resistant types of cancers do not respond well to conventional therapies. To treat and enhance the efficacy of drug delivery for these cancers, we have developed an in vitro model of a combination therapy using adult human mesenchymal stem cells, electrical pulses and chemo drug. Adult Mesenchymal stem cells were used because they are similar to cancer stem cells

Sankaranarayanan Kavitha; Ramachandran Raja Prabhu; Kumar Raghavan; Muralitharen Sinthu; S. Mansoor Usman; M. Sriram Kumar; V. Madan Kumar; S. Vignesh; V. Malini; K. M. Cherian; S. Madhivanan; Sankaranarayanan Karthik; Natarajan Arutselvan; Sundararajan Raji

2011-01-01

101

Myocardial infarction and stem cells.  

PubMed

Permanent loss of cardiomyocytes and scar tissue formation after myocardial infarction (MI) results in an irreversible damage to the cardiac function. Cardiac repair (replacement, restoration, and regeneration) is, therefore, essential to restore function of the heart following MI. Existing therapies lower early mortality rates, prevent additional damage to the heart muscle, and reduce the risk of further heart attacks. However, there is need for treatment to improve the infarcted area by replacing the damaged cells after MI. Thus, the cardiac tissue regeneration with the application of stem cells may be an effective therapeutic option. Recently, interest is more inclined toward myocardial regeneration with the application of stem cells. However, the potential benefits and the ability to improve cardiac function with the stem cell-based therapy need to be further addressed. In this review, we focus on the clinical applications of stem cells in the cardiac repair. PMID:21687345

Krishna, K Ananda; Krishna, K Sai; Berrocal, Ruben; Rao, K S; Sambasiva Rao, K R S

2011-04-01

102

International Stem Cell Tourism and the Need for Effective Regulation: Part I: Stem Cell Tourism in Russia and India: Clinical Research, Innovative Treatment, or Unproven Hype?  

Microsoft Academic Search

Persons with serious and disabling medical conditions have trav- eled abroad in search of stem cell treatments in recent years. However, weak or nonexistent oversight systems in some countries provide insufficient patient protections against unproven stem cell treatments, raising concerns about expo- sure to harm and exploitation. The present article, the first of two, describes and analyzes stem cell tourism

Cynthia B. Cohen; Peter J. Cohen

2010-01-01

103

International Stem Cell Tourism and the Need for Effective Regulation: Part I: Stem Cell Tourism in Russia and India: Clinical Research, Innovative Treatment, or Unproven Hype?  

Microsoft Academic Search

Persons with serious and disabling medical conditions have traveled abroad in search of stem cell treatments in recent years. However, weak or nonexistent oversight systems in some countries provide insufficient patient protections against unproven stem cell treatments, raising concerns about exposure to harm and exploitation. The present article, the first of two, describes and analyzes stem cell tourism in Russia

Cynthia B. Cohen; Peter J. Cohen

2010-01-01

104

Gastric epithelial stem cells.  

PubMed

Advances in our understanding of stem cells in the gastrointestinal tract include the identification of molecular markers of stem and early progenitor cells in the small intestine. Although gastric epithelial stem cells have been localized, little is known about their molecular biology. Recent reports describe the use of inducible Cre recombinase activity to indelibly label candidate stem cells and their progeny in the distal stomach, (ie, the antrum and pylorus). No such lineage labeling of epithelial stem cells has been reported in the gastric body (corpus). Among stem cells in the alimentary canal, those of the adult corpus are unique in that they lie close to the lumen and increase proliferation following loss of a single mature progeny lineage, the acid-secreting parietal cell. They are also unique in that they neither depend on Wnt signaling nor express the surface marker Lgr5. Because pathogenesis of gastric adenocarcinoma has been associated with abnormal patterns of gastric differentiation and with chronic tissue injury, there has been much research on the response of stomach epithelial stem cells to inflammation. Chronic inflammation, as induced by infection with Helicobacter pylori, affects differentiation and promotes metaplasias. Several studies have identified cellular and molecular mechanisms in spasmolytic polypeptide-expressing (pseudopyloric) metaplasia. Researchers have also begun to identify signaling pathways and events that take place during embryonic development that eventually establish the adult stem cells to maintain the specific features and functions of the stomach mucosa. We review the cytologic, molecular, functional, and developmental properties of gastric epithelial stem cells. PMID:21144849

Mills, Jason C; Shivdasani, Ramesh A

2010-12-07

105

Effect of age and gender on cell proliferation and cell surface characterization of synovial fat pad derived mesenchymal stem cells.  

PubMed

Cell based therapies are being investigated for biological repair of a variety of disorders. Previous work has shown that mesenchymal stem cells (MSCs) from older patients have reduced proliferation rates. As age is associated with greater musculoskeletal morbidity, e.g., osteoarthritis, an optimal MSC expansion strategy is required for older patients. In this in vitro study we investigate how age and gender affect MSC proliferation rate and cell surface characterization, as well as identify a relationship between seeding density and proliferation that could be applied to therapeutic MSC uses. Synovial fat pad derived MSCs were isolated and expanded from 14 patients undergoing total knee replacements. The cells were seeded at densities between 50 and 10,000 cells/cm(2) and cell proliferation studies, flow cytometry, and cell surface staining were performed. Females were found to have consistently higher cell proliferation and cell surface marker expression. The cell surface marker CD105 had a constant expression irrespective of age. A statistically significant inverse relationship was found between seeding densities and cell proliferation rates. This study has shown that patient characteristics do effect cell proliferation rate and cell surface characterization, but as seeding density has a significant relationship with proliferation rate, it can be altered, possibly along with other cell culturing strategies, to compensate for the effects of patient factors on MSCs. We have also shown that gender affects cell proliferation and cell surface characterization, something most previous studies may have failed to identify as they group male and female patients together. PMID:22228598

Fossett, Emma; Khan, Wasim S; Longo, Umile Giuseppe; Smitham, Peter J

2012-01-06

106

The Neural Stem Cells  

Microsoft Academic Search

\\u000a Neural stem cells represent a heterogeneous population of mitotically active, self-renewing and multipotent cells of both\\u000a the developing and the adult central nervous system (CNS) showing complex patterns of gene expression that may vary in both\\u000a space and time. Endogenous stem cells residing within CNS germinal niches might concur to nervous system repair owing to their\\u000a ability to drive neurogenesis

Stefano Pluchino; Marco Bacigaluppi; Elena Brini; Erica Butti; Chiara Cossetti; Melania Cusimano; Lucia Zanotti; Gianvito Martino

107

Cryopreservation of Stem Cells  

Microsoft Academic Search

Institutional achievements in research of low temperature preservation of stem cells derived from fetal and adult sources\\u000a are presented in the report. Special attention is attended to cryopreservation of pretenders on hemopoietic stem cells from\\u000a human cord blood and fetal liver. Examining of viability of cryopreserved with DMSO fetal liver cells of specific phenotype\\u000a by parallel determining with vital dye

Valentin I. Grischenko; Lubov A. Babiychik; Alexander Yu. Petrenko

108

Leukemia Stem Cells  

Microsoft Academic Search

\\u000a Normal hematopoiesis develops hierarchically from a hematopoietic stem cell, which is defined by both extensive self-renewal\\u000a capacity and multi-lineage potential, i.e. the ability to give rise to fully differentiated cells of all hematopoietic lineages.\\u000a Since leukemia can be considered as malignant hematopoiesis, the existence of a developmental hierarchy in leukemia with a\\u000a malignant stem cell at its apex was postulated

Markus Müschen

109

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

PubMed Central

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

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

2012-01-01

110

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

PubMed

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

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

2012-07-28

111

Therapeutic effects of human adipose stem cell-conditioned medium on stroke.  

PubMed

Stem cell therapy is a promising approach for stroke. However, low survival rates and potential tumorigenicity of implanted cells could undermine the efficacy of the cell-based treatment. The use of stem cell-conditioned medium (CM) may be a feasible approach to overcome these limitations. Especially, specific stem cell culture condition and continuous infusion of CM into ischemic brains would have better therapeutic results. The CM was prepared by culturing human adipose-derived stem cells in a three-dimensional spheroid form to increase the secretion of angiogenic/neuroprotective factors. Ischemic stroke was induced by standard middle cerebral artery occlusion methods in the brain of 8-week-old Sprague-Dawley rats. Continuous infusion of CM or ?MEM media (0.5 ?l/hr) into the lateral ventricle was initiated 8 days after the surgery and maintained for 7 days. Alteration in the motor function was monitored by the rotarod test. Infarction volume and the number of microvessels or TUNEL-positive neural cells were analyzed 15 days after the surgery. Compared with ?MEM, continuous CM infusion reduced the infarction volume and maintained motor function. The number of CD31-positive microvessels and TUNEL-positive neural cells significantly increased and decreased, respectively, in the penumbra regions. Although the apoptosis of all neural cell types decreased, reduction in the microglial apoptosis and astrogliosis was prominent and significant. In this study, the therapeutic effects of the CM against stroke were confirmed in an animal model. Increased endothelial cell proliferation, reduced neural cell apoptosis, and milder astrogliosis may play important roles in the treatment effects of CM. PMID:22535477

Cho, Yu Jin; Song, Hyeon Suk; Bhang, Sukho; Lee, Saehyoung; Kang, Bong Gu; Lee, Jae Chul; An, Jaeyeol; Cha, Choong Ik; Nam, Do-Hyun; Kim, Byung Soo; Joo, Kyeung Min

2012-04-26

112

Stem cell-derived in vitro models for investigating the effects of endocrine disruptors on developing neurons and neuroendocrine cells.  

PubMed

Neuroendocrine cells are a set of specialized hormone-releasing neurons that control most vital functions in humans and wildlife, such as growth, reproduction, metabolism, and stress responses. Increasing evidence points to neuroendocrine cells as the primary neuronal target of endocrine disruptors. Endocrine disruption appears to be most significant during prenatal and early postnatal development. However, limitations with traditional cell culture models of neuronal development led to a lack of understanding regarding the mechanisms by which endocrine disruptors affect neurodevelopment. In recent years, Stem Cell-derived neuronal models have become available and may offer distinct advantages over other in vitro model systems for investigating the effects of endocrine disruptors on the developing brain. Further, recently new models of Stem Cell-derived neuroendocrine cells that may provide more effective ways for studying the effects of endocrine disruptors directly on developing neuroendocrine cells in vitro were developed. This constitutes a review of currently available cell models of developing neurons that have been used to investigate in vitro effects of endocrine disruptors on developing brain. The review also presents recently developed models of Stem Cell-derived neuroendocrine cells that might be used to investigate in vitro effects of endocrine disruptors and their mechanisms of action directly on the developing neuroendocrine cells. PMID:21790313

El Majdoubi, Mohammed

2011-01-01

113

Effects of homocysteine on ERK signaling and cell proliferation in fetal neural stem cells in vitro.  

PubMed

The aim of the present study was to determine if the excitatory amino acid homocysteine (Hcy) alters ERK signaling and cell proliferation in fetal neural stem cells (NSCs) in vitro. NSCs were isolated from fetal rats and grown in serum-free suspension medium. The cells were identified as NSCs by their expression of immunoreactive Sox2. NSCs were assigned to one of four treatment groups: vehicle control, low-dose Hcy group (Hcy-L, medium contained 30 ?mol/L Hcy), middle-dose Hcy group (Hcy-M, 100 ?mol/L Hcy) and high-dose Hcy group (Hcy-H, 300 ?mol/L Hcy). Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Protein expression levels of ERK1/2 and phosphorylated ERK1/2 were detected by Western blot. The effects of Hcy on NSC death, including apoptosis, were assessed by using flow cytometry and trypan blue exclusion. The results showed that NSCs grew as neurospheres in the serum-free medium. Hcy decreased ERK1/2 protein phosphorylation and NSC proliferation, but it did not induce cell death or apoptosis within the concentration from 30 to 300 ?mol/L. The above results are consistent with the hypothesis that Hcy decreases fetal NSC proliferation by inhibiting ERK signaling. PMID:23109178

Yan, Hai; Zhang, Xumei; Luo, Suhui; Liu, Huan; Wang, Xuan; Gao, Yuxia; Wilson, John X; Huang, Guowei

2013-05-01

114

Stem Cell Task Force  

NSDL National Science Digital Library

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

115

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

PubMed

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

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

2002-03-01

116

Intestinal Stem Cells  

PubMed Central

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

2010-01-01

117

Cardiac stem cell therapy: stemness or commitment?  

PubMed

Cardiac stem cell therapy to promote engraftment of de novo beating cardiac muscle cells in cardiomyopathies could potentially improve clinical outcomes for many patients with congestive heart failure. Clinical trials carried out over the last decade for cardiac regeneration have revealed inadequacy of current approaches in cell therapy. Chief among them is the choice of stem cells to achieve the desired outcomes. Initial enthusiasm of adult bone marrow stems cells for myocyte regeneration has largely been relegated to paracrine-driven, donor cell-independent, endogenous cardiac repair. However, true functional restoration in heart failure is likely to require considerable myocyte replacement. In order to match stem cell application to various clinical scenarios, we review the necessity to preprime stem cells towards cardiac fate before myocardial transplantation and if these differentiated stem cells could confer added advantage over current choice of undifferentiated stem cells. We explore differentiation ability of various stem cells to cardiac progenitors/cardiomyocytes and compare their applicability in providing targeted recovery in light of current clinical challenges of cell therapy. PMID:22943934

Mehta, Ashish; Shim, Winston

2012-08-27

118

Periosteum as a source of mesenchymal stem cells: the effects of TGF-?3 on chondrogenesis  

PubMed Central

INTRODUCTION: Numerous experimental efforts have been undertaken to induce the healing of lesions within articular cartilage by re-establishing competent repair tissue. Adult mesenchymal stem cells have attracted attention as a source of cells for cartilage tissue engineering. The purpose of this study was to investigate chondrogenesis employing periosteal mesenchymal cells. METHODS: Periosteum was harvested from patients who underwent orthopedic surgeries. Mesenchymal stem cells were characterized through flow cytometry using specific antibodies. The stem cells were divided into four groups. Two groups were stimulated with transforming growth factor ?3 (TGF-?3), of which one group was cultivated in a monolayer culture and the other was cultured in a micromass culture. The remaining two groups were cultivated in monolayer or micromass cultures in the absence of TGF-?3. Cell differentiation was verified through quantitative reverse transcription-polymerase chain reaction (RT-PCR) and using western blot analysis. RESULT: In the groups cultured without TGF-?3, only the cells maintained in the micromass culture expressed type II collagen. Both the monolayer and the micromass groups that were stimulated with TGF-?3 expressed type II collagen, which was observed in both quantitative RT-PCR and western blot analysis. The expression of type II collagen was significantly greater in the micromass system than in the monolayer system. CONCLUSION: The results of this study demonstrate that the interactions between the cells in the micromass culture system can regulate the proliferation and differentiation of periosteal mesenchymal cells during chondrogenesis and that this effect is enhanced by TGF-?3.

de Mara, Cristiane Sampaio; Sartori, Angelica Rossi; Duarte, Adriana Silva; Lugani Andrade, Andre Luis; Camargo Pedro, Marcio Amaral; Coimbra, Ibsen Bellini

2011-01-01

119

The effect of topology of chitosan biomaterials on the differentiation and proliferation of neural stem cells  

Microsoft Academic Search

Neural stem cells (NSCs) are capable of self-renewal and differentiation into three principle central nervous system cell types under specific local microenvironments. Chitosan films (Chi-F), chitosan porous scaffolds (Chi-PS) and chitosan multimicrotubule conduits (Chi-MC) were used to investigate their effects on the differentiation and proliferation of NSCs isolated from the cortices of fetal rats. In the presence of 10% fetal

Gan Wang; Qiang Ao; Kai Gong; Aijun Wang; Lu Zheng; Yandao Gong; Xiufang Zhang

2010-01-01

120

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

Microsoft Academic Search

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

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

2009-01-01

121

Stem Cells for Neurovascular Repair in Stroke  

PubMed Central

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

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

2013-01-01

122

Stem cell plasticity  

Microsoft Academic Search

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

Uma Lakshmipathy; Catherine Verfaillie

2005-01-01

123

Embryonic stem cells  

Microsoft Academic Search

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

H. J. Rippon; A. E. Bishop

2004-01-01

124

Clonal interrogation of stem cells  

Microsoft Academic Search

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

Kristin Hope; Mickie Bhatia

2011-01-01

125

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

PubMed Central

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.

2010-01-01

126

Laser biomodulation on stem cells  

Microsoft Academic Search

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

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

2001-01-01

127

Mathematical models of marrow cell kinetics: Differential effect of protracted irradiations on stromal and stem cells in mice  

SciTech Connect

This paper describes comparisons between the authors' results (from maximum-likelihood estimation techniques for cellular damage, repair, and compensatory repopulation) and published experimental data on marrow stromal cells. After biophysical consideration of the rate constants that were derived by maximizing the likelihood function (a consideration necessary to extend the model to cell populations not indicated by the model as [open quotes]critical[close quotes] for recovery), the rate constants for cellular damage to stem cells are fitted to experimental data. Rate constants for repair and proliferation of stem cells are assigned based on published data on repair/proliferation halftimes, and these assignments affect the evaluation of the rate constants for cellular damage. From the two models, that is one for [open quotes]critical[close quotes] cells (having radiosensitive and repopulation characteristics similar to stromal cells) and another for stem cells, effects on two cell populations of different radiosensitivities and repopulation rates can be demonstrated for complex schedules of protracted irradiations which could reduce either cell population below a critical need for marrow repopulation. Analysis of animal mortality data has indicated that recovery of an animal from potentially lethal irradiation is dominantly by cells with survival and repopulation characteristics similar to those of stroma cells. In contrast to the surviving fraction of hematopoietic stem cells, it appears that the probability of an animal's recovery is high if the [open quotes]critical[close quotes] population of cells is above 1% (our [open quotes]best[close quotes] maximum likelihood estimate, from mouse data, with the corresponding lower confidence bound at about 0.2%). Of course, a few stem cells-perhaps only one-must maintain a potential for repopulation of blood and marrow. 83 refs., 4 figs., 3 tabs.

Jones, T.D.; Morris, M.D. (Oak Ridge National Lab., TN (United States)); Young, R.W. (Defense Nuclear Agency, Washington, DC (United States))

1993-08-01

128

Interventions in Aging and Neurodegenerative Disease: Effects on Adult StemCells  

Microsoft Academic Search

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

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

129

Brain Tumor Stem Cells  

Microsoft Academic Search

Primary malignant brain cancer, one of the most deadly diseases, has a high rate of recurrence after treatment. Studies in\\u000a the past several years have led to the hypothesis that the root of the recurrence may be brain tumor stem cells (BTSCs), stem-like\\u000a subpopulation of cells that are responsible for propagating the tumor. Current treatments combining surgery and chemoradiotherapy\\u000a could

Zhigang Xie

2009-01-01

130

Cardiac stem cell senescence.  

PubMed

Cellular senescence processes affecting tissue resident stem cells are considered, at present, an hallmark of both aging and age-related pathologies. Therefore it is mandatory to address this problem with adequate techniques that could highlight the molecular alterations associated with this complex cellular response to stressors. Here we describe methods to characterize cardiac stem cell (CSC) senescence from a molecular and functional standpoint. PMID:23400436

Cesselli, Daniela; D'Aurizio, Federica; Marcon, Patrizia; Bergamin, Natascha; Beltrami, Carlo Alberto; Beltrami, Antonio Paolo

2013-01-01

131

The effects of topographical patterns and sizes on neural stem cell behavior.  

PubMed

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

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

2013-03-18

132

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

PubMed Central

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

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

2013-01-01

133

[Biological effects and potential applications of mesenchymal stem cell culture under low oxygen pressure].  

PubMed

As for hemopoietic stem cells, it is thought although not formally demonstrated that bone marrow mesenchymal stem cells (BMMSC) reside in a specific microenvironment or niche characterized by a low O(2) tension. In support of this hypothesis is the observation that MSC can be amplified in vitro under 1-8% O(2) while retaining multipotent capacities. Culture in hypoxic condition may therefore be useful in therapy as the low number of MSC is a major limitation to their use in regenerative medicine and to a lesser extent in the treatment of some autoimmune and overt inflammatory diseases. However hypoxia may modify MSC with significant effects on their metabolism and gene expression hence modifications in their differentiation abilities to mature in specialized cells. This review discusses the various effects of hypoxia on the fate and behavior of MSC and potential clinical applications of culture under hypoxic conditions in regenerative medicine and immune/inflammatory disorders. PMID:21907502

Némos, C; Basciano, L; Dalloul, A

2011-09-09

134

Hormonal control of stem cell systems.  

PubMed

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

Gancz, Dana; Gilboa, Lilach

2013-07-22

135

Limbal Stem Cells in Review  

PubMed Central

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

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

2009-01-01

136

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

PubMed Central

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

2013-01-01

137

Germline stem cells.  

PubMed

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

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

2011-11-01

138

Brain tumour stem cells  

Microsoft Academic Search

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

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

2006-01-01

139

Effects of estrogen on the proportion of stem cells in the breast  

Microsoft Academic Search

There is increasing evidence that breast cancers contain tumor-initiating cells with stem cell properties. The importance\\u000a of estrogen in the development of the mammary gland and in breast cancer is well known, but the influence of estrogen on the\\u000a stem cell population has not been assessed. We show that estrogen reduces the proportion of stem cells in the normal human

Bruno M. Simőes; Marco Piva; Oihana Iriondo; Valentine Comaills; Jose A. López-Ruiz; Ińaki Zabalza; Jon A. Mieza; Olga Acinas; Maria d. M. Vivanco

2011-01-01

140

Effect of stem cell transplantation for B-cell malignancies on disease course of associated polyneuropathy.  

PubMed

B cell dyscrasias are often refractory to medical treatments, and hematological stem cell therapy (SCT) may be warranted. It is not clear whether an associated polyneuropathy may also profit from SCT. In exceptional cases SCT has been tried in patients with monoclonal gammopathy and progressive polyneuropathy refractory to medical treatments. In a cohort of 225 patients with monoclonal gammopathy and polyneuropathy, we selected the six patients who underwent SCT and retrospectively examined the effects of SCT on the disease course of the associated polyneuropathy. In all patients except one, the indication for SCT was hemato-oncological (multiple myeloma in 4 patients and primary AL amyloidosis in 1). The remaining patient had an IgG monoclonal gammopathy of undetermined significance and a progressive and painful polyneuropathy for which she was treated with SCT. SCT led to improvement of motor scores and autonomic symptoms in one patient; three patients experienced improvement of neuropathic pain or sensory deficits but showed further progression of weakness. One patient showed no improvement at all. One patient died within 100 days after SCT. In conclusion, SCT as a treatment of refractory hematological malignancy may occasionally have a positive effect on the associated progressive polyneuropathy, although the benefits are very limited and the treatment-related mortality is high. PMID:22399147

Stork, A C J; van der Pol, W L; van Kessel, D; Lokhorst, H M; Notermans, N C

2012-03-08

141

Morphofunctional study of the therapeutic effect of autologous mesenchymal stem cells in experimental diffuse brain injury in rats  

Microsoft Academic Search

Effects of systemic transplantation of mesenchymal stem cells obtained by culturing of autologous bone marrow on proliferative\\u000a activity of cells and functional morphology of neurons after diffuse brain injury were studied in Wistar rats. Comparative\\u000a analysis of the results indicated that systemic injection of mesenchymal stem cells in a syngeneic organism produced proliferotropic,\\u000a angiogenic, and, presumably, neurotrophic effects. The therapeutic

A. F. Tsyb; L. M. Roshal’; V. V. Yuzhakov; A. G. Konoplyannikov; G. N. Sushkevich; L. N. Bandurko; I. E. Ingel’; Zh. B. Semenova; O. A. Konoplyannikova; L. A. Lepekhina; S. Sh. Kal’sina; Yu. G. Verkhovskii; A. S. Shevchuk; I. V. Semenkova

2006-01-01

142

Topographic effect on human induced pluripotent stem cells differentiation towards neuronal lineage.  

PubMed

Pluripotent stem cells have the potential to develop into all cell types of the adult body. Besides chemical and mechanical cues, topographical effect of surfaces could also contribute to the development of new therapies in regenerative medicine. In the present study, we tested the effects of nanograting substrates with different widths (width:350 nm/2 ?m/5 ?m, height: 300 nm) on human induced pluripotent stem cells (hiPSCs), in particular regarding the commitment of stem cell differentiation to desired phenotypes. We found that nuclei of hiPSCs could align and elongate in the direction of the nano/microstructure, whereas they distributed randomly on flat surfaces. The contact guidance significantly increased when the cells were cultured on the surface with smaller pitch. Gene expression profiling by real-time PCR and immunostaining showed significant up-regulation of neuronal markers on nanostructured substrates either with solely topographical cues or combined with pre-neuronal induction. A width of 350 nm, in particular, induced highest neuronal marker expression. This study demonstrates the significance of topography, especially regarding the width of the structures, in directing differentiation of hiPSCs towards the neuronal lineage. Our study suggests the potential applications of surface topography in clinical regenerative medicine for nerve injury repair. PMID:23891397

Pan, Fei; Zhang, Miao; Wu, Guangming; Lai, Yuekun; Greber, Boris; Schöler, Hans R; Chi, Lifeng

2013-07-23

143

Effect of lead on proliferation and neural differentiation of mouse bone marrow-mesenchymal stem cells.  

PubMed

Bone marrow-mesenchymal stem cells (MSCs) are considered to be an ideal source of stem cells for assessing the effects of environmental toxins on the proliferation, multipotency and differentiation of adult stem cells. The aim of this study was to investigate the effect of lead on the proliferation and neuronal differentiation of murine MSCs. MTT assay used in this study revealed that while the proliferation of MSCs is sensitive to higher than 10 microM lead, a 50% reduction in the rate of their proliferation can be achieved in the presence of 60 microM lead. The results of immunocytochemistry and RT-PCR showed that beta-mercaptoethanol induced-neuronal differentiation is also reduced after the treatment of MSCs by 60 microM lead. Furthermore, the comet assay analysis of MSCs showed a substantial increase in DNA damage in the lead treated cells compared to the control. In conclusion our results revealed for the first time that lead is not only cytotoxic to the survival and proliferation of MSCs but also inhibits their differentiation to neurons in a dose-dependant manner. Therefore, MSCs appear to be an alternative method for assessing the cytotoxic effects of such environmental hazards. PMID:18381235

Kermani, Shabnam; Karbalaie, Khadijeh; Madani, Seyed Hossein; Jahangirnejad, Ali Akbar; Eslaminejad, Mohamadreza Baghaban; Nasr-Esfahani, Mohammad Hossein; Baharvand, Hossein

2008-02-21

144

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

PubMed

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

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

2012-11-16

145

The chiaroscuro stem cell: a unified stem cell theory  

Microsoft Academic Search

reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with cell cycle transit. If the phenotype of these primitive marrow cells changes from engraftable stem cell to progenitor and back to engraftable stem cell with cycle transit, then this suggests that the identity of the engraft- able stem cell may be partially masked in nonsynchronized

Peter J. Quesenberry; Gerald A. Colvin; Jean-Francois Lambert

2002-01-01

146

Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1?  

Microsoft Academic Search

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1? (SDF-1?) is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1? were explored. 6-hydroxydopamine (6-OHDA, 20 ?g) was injected into the right striatum of female SD rats

Feifei Wang; Takao Yasuhara; Tetsuro Shingo; Masahiro Kameda; Naoki Tajiri; Wen Ji Yuan; Akihiko Kondo; Tomohito Kadota; Tanefumi Baba; Judith Thomas Tayra; Yoichiro Kikuchi; Yasuyuki Miyoshi; Isao Date

2010-01-01

147

The effect of incorporation of SDF-1alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response.  

PubMed

Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design. Recent evidence supports that mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC) can have beneficial effects which alter the inflammatory responses and improve healing. The purpose of this study was to examine whether stem cells could be targeted to the site of biomaterial implantation and whether increasing local stem cell responses could improve the tissue response to PLGA scaffold implants. Through incorporation of SDF-1alpha through factor adsorption and mini-osmotic pump delivery, the host-derived stem cell response can be improved resulting in 3X increase in stem cell populations at the interface for up to 2 weeks. These interactions were found to significantly alter the acute mast cell responses, reducing the number of mast cells and degranulated mast cells near the scaffold implants. This led to subsequent downstream reduction in the inflammatory cell responses, and through altered mast cell activation and stem cell participation, increased angiogenesis and decreased fibrotic responses to the scaffold implants. These results support that enhanced recruitment of autologous stem cells can improve the tissue responses to biomaterial implants through modifying/bypassing inflammatory cell responses and jumpstarting stem cell participation in healing at the implant interface. PMID:20185171

Thevenot, Paul T; Nair, Ashwin M; Shen, Jinhui; Lotfi, Parisa; Ko, Cheng-Yu; Tang, Liping

2010-02-24

148

Effects of preservation time on proliferative potential of human limbal stem/progenitor cells  

PubMed Central

AIM To determine the proliferative potential and the maintenance of stem cell activity in stored human limbal tissues, and correlate this with the preservation time, cell viability and the expression of stem cell markers. METHODS Thirty limbal rims were split into 4 parts and stored in corneal preservation medium at 4°C for 0, 1, 4, or 7 days. The limbal stem cell and mitotic markers P63, CK19, proliferating cell nuclear antigen (PCNA), and Ki67 were determined by immunohistochemical staining. The proliferative potential of limbal epithelial cells was assessed by cell viability, the ability of generating stratified epithelium, and colony forming assay. RESULTS The stored tissues maintained limbal stratified structure to 7 days and exhibited comparable expression level of stem cell and mitotic markers. The proportion of viable cells decreased with the prolonged preservation time, while colony forming efficiency decreased from the 1st day and disappeared at the 4th day. When inoculated on amniotic membrane, the cells preserved for 1 day formed a stratified epithelium, while the cells from 4 days' preservation formed a discontinuous layer. CONCLUSION The colony forming efficiency of limbal epithelial stem/progenitor cells decreased rapidly with the increasing preservation time, while the expression level of markers and capacity of forming epithelial monolayer on amniotic membrane decreased gradually. The limbal epithelial stem cells lost their function earlier than the lost expression level of stem cell markers. This may help us to better choose the appropriate preservation grafts for future limbal stem cell transplantation.

Liu, Ting; Wang, Yao; Duan, Hao-Yun; Qu, Ming-Li; Yang, Ling-Ling; Xu, Yuan-Yuan; Zang, Xin-Jie; Zhou, Qing-Jun

2012-01-01

149

Paracrine Effects of Adipose-Derived Stem Cells on Keratinocytes and Dermal Fibroblasts  

PubMed Central

Background Adipose-derived stem cells (ASCs) are mesenchymal stem cells that have recently been applied to tissue repair and regeneration. Keratinocytes and dermal fibroblasts play key roles in cutaneous wound healing. Objective We investigated the paracrine effects of ASCs on HaCaT cells (i.e., immortalized human keratinocytes) and human dermal fibroblasts to explore the mechanism of the effects of ASCs on cutaneous wound healing. Methods HaCaT cells and primary cultured human dermal fibroblasts were treated with 50% conditioned medium of ASCs (ASC-CM). Viability, in vitro wound healing, and fibroblast-populated collagen lattice contraction assays were conducted, and reverse transcription-polymerase chain reaction (RT-PCR) for the type I procollagen ?1 chain gene was performed. Results The proliferation of HaCaT cells and fibroblasts was increased by ASC-CM in the viability assay. ASC-CM promoted in vitro wound healing of HaCaT cells and increased the contraction of the fibroblast-populated collagen lattice. RT-PCR showed that the transcription of the type I procollagen ?1 chain gene in fibroblasts was upregulated by ASC-CM. Conclusion The stimulatory effect of ASC on cutaneous wound healing may be partially mediated by paracrine effects of ASCs on other skin cells. Application of ASCs or ASC-derived molecules could be an innovative therapeutic approach in the treatment of chronic wounds and other conditions.

Lee, Seung Ho; Jin, Sang Yun; Song, Jin Seok; Seo, Kyle K.

2012-01-01

150

Challenges for heart disease stem cell therapy  

PubMed Central

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

Hoover-Plow, Jane; Gong, Yanqing

2012-01-01

151

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

Microsoft Academic Search

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

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

2008-01-01

152

The effects of a simplified method for cryopreservation and thawing procedures on peripheral blood stem cells  

Microsoft Academic Search

A simplified method for cryopreservation at ?80°C of peripheral blood stem cells (PBSC) has been increasingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has several advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is known about effects

Y Katayama; T Yano; A Bessho; S Deguchi; K Sunami; N Mahmut; K Shinagawa; E Omoto; S Makino; T Miyamoto; S Mizuno; T Fukuda; T Eto; T Fujisaki; Y Ohno; S Inaba; Y Niho; M Harada

1997-01-01

153

Effect of electromagnetic fields on proliferation and differentiation of cultured mouse bone marrow mesenchymal stem cells  

Microsoft Academic Search

Summary  In order to study the effects of electromagnetic fields (EMFs) on proliferation, differentiation and intercellular cyclic\\u000a AMP (cAMP) in mouse bone marrow mesenchymal stem cells (MSCs)in vitro, the mouse bone MSCs were isolated and culturedin vitro. The third passage MSCs were divided into 4 groups and stimulated with EMFs. The cellular proliferation (MTT), the cellular\\u000a differentiation (alkaline phosphatase activity, ALP),

Wu Hua; Ren Kai; Zhao Wenchun; Ge Baojian; Peng Songlin

2005-01-01

154

Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells  

Microsoft Academic Search

Adult mesenchymal stem cells (MSCs) have been suggested to decrease lymphocyte proliferation in vitro. We hypothesised that foetal MSCs (fMSCs) would have an immunosuppressive effect on allograft responses in vitro. Human MSCs were isolated and cultured from first-trimester foetal livers and characterised by flow cytometry. fMSC stained positive for CD29, CD44, CD166, CD105, SH-3 and SH-4, and negative for CD14,

C Götherström; O Ringdén; M Westgren; C Tammik; K Le Blanc

2003-01-01

155

Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptor? activation.  

PubMed

Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPAR? and PTEN, and a reduction of pSer84PPAR?, pERK1/2, and PPAR?. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPAR? agonist GW7845 and insensitivity to PPAR? agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPAR? expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPAR?. PMID:21955520

Yuan, Hongyan; Upadhyay, Geeta; Yin, Yuzhi; Kopelovich, Levy; Glazer, Robert I

2011-09-28

156

Stem Cell Antigen-1 Deficiency Enhances the Chemopreventive Effect of Peroxisome Proliferator-Activated Receptor? Activation  

PubMed Central

Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPAR? and PTEN, and a reduction of pSer84PPAR?, pERK1/2 and PPAR?. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPAR? agonist GW7845 and insensitivity to PPAR? agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPAR? expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPAR?.

Yuan, Hongyan; Upadhyay, Geeta; Yin, Yuzhi; Kopelovich, Levy; Glazer, Robert I.

2011-01-01

157

Therapeutic effect of genetically modified human neural stem cells encoding cytosine deaminase on experimental glioma.  

PubMed

The aim of this study was to determine the efficacy of neural stem cell-based suicidal gene therapy in rats bearing human glioma. F3 human neural stem cells (NSCs) were transduced to encode cytosine deaminase (CD) which converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). Intratumoral or intravenous transplantation of F3.CD human NSCs led to marked reduction in tumor burden and significantly prolonged the survival of brain tumor-bearing rats. The systemic administration of 5-FC with direct intratumoral/intravenous transplantation of F3.CD cells had remarkable therapeutic effect in rats with human glioma cells as compared with transplantation of parental F3 cells. There was 74% reduction in tumor volume in rats receiving direct transplantation of F3.CD cells into tumor site, and 67% reduction in tumor volume in rats receiving intravenous injection of F3.CD cells as compared to control animals transplanted with human glioma U373 cells alone. The combination of F3.CD and 5-FC was a highly effective in the glioma rat model. Our observations suggest that genetically engineered NSCs encoding suicide gene CD could provide clinical application of suicide gene therapy for patients with glioma. PMID:22177952

Kim, Jae Ho; Kim, Jin Young; Kim, Seung U; Cho, Kyung Gi

2011-12-08

158

Effects of Human Adipose-derived Stem Cells on Cutaneous Wound Healing in Nude Mice  

PubMed Central

Background Despite numerous treatments available for deteriorated cutaneous wound healing such as a diabetic foot, there is still the need for more effective therapy. Adipose-derived stem cells (ASCs) are mesenchymal stem cells, which are self-renewing and multipotent. Mesenchymal stem cells have the potential for tissue repair and regeneration. Objective To investigate the effects of human ASCs on the healing of cutaneous wounds in nude mice. Methods 15-mm round full-thickness skin defects were generated on the back of BALB/c nude mice. The mice were divided into three groups for wound coverage: (i) human ASCs-populated collagen gel, (ii) human dermal fibroblasts-populated collagen gel, and (iii) collagen gel alone. Wound contraction was prevented with a splint method. Wound size was measured 10 days after injury. At 28 days histological analysis was performed. Results Both ASCs and dermal fibroblasts accelerated wound closure, but dermal fibroblasts were more effective than ASCs. At 28 days, the dermal portion of ASCs or dermal fibroblasts wound scars were thicker than collagen gel wound scars. Conclusion ASCs and dermal fibroblasts stimulate cutaneous wound healing and improve scar thickness.

Lee, Seung Ho; Lee, Joon Ho

2011-01-01

159

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

PubMed Central

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

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

2012-01-01

160

Opposing effect of mesenchymal stem cells on Th1 and Th17 cell polarization according to the state of CD4 + T cell activation  

Microsoft Academic Search

Mesenchymal stem cells (MSCs) are multipotent progenitors with broad immunosuppressive properties. However, their therapeutic use in autoimmune disease models has shown dissimilar effects when applied at different stages of disease. We therefore investigated the effect of the addition of MSCs on the differentiation of Th1, Treg and Th17 cells in vitro, at different states of CD4+ T cell activation. CD4+

Flavio Carrión; Estefania Nova; Patricia Luz; Felipe Apablaza; Fernando Figueroa

2011-01-01

161

Human embryonic stem cells  

Microsoft Academic Search

The property of pluripotency confers the capacity for differentiation into a large number of cell types including extra-embryonic,\\u000a somatic and germinal cells. During normal development, pluripotency is acquired by the cells of the early embryo, which shortly\\u000a thereafter undergo differentiation, whereas embryonic stem cells (ESCs) uniquely maintain pluripotency while undergoing extensive\\u000a in vitro proliferation. Studies using ESCs have begun to

Ludovic Vallier; Roger A. Pedersen

2005-01-01

162

Brain cancer stem cells  

Microsoft Academic Search

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

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

2009-01-01

163

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

PubMed Central

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

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

2009-01-01

164

Post-irradiation protective effect of irsogladine maleate on intestinal crypt stem cells in mice.  

PubMed

Radioprotective effect of irsogladine maleate, an anti-ulcer drug, on the intestinal crypt stem cell survival was studied in mice using a crypt microcolony assay. Irsogladine maleate was injected intraperitoneally immediately after irradiation and then, daily for three days. A successive administration of the drug following 10 Gy of irradiation increased the survival of intestinal stem cells with a clear dose-related trend. In order to estimate the D0, survival curves were determined for X-ray plus placebo and X-ray plus 10 mg/kg of irsogladine maleate. The D0, for X-ray plus the drug was 2.2 Gy while it was 1.9 Gy for X-ray plus placebo. These findings suggest that isogladine maleate can be applied for the alleviation of intestinal damages in heavily irradiated people by radiation accidents. PMID:1481123

Kurishita, A; Takai, Y; Ueda, F; Sakamoto, K; Ono, T

1992-12-01

165

Stem cells and the Planarian Schmidtea mediterranea  

Microsoft Academic Search

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

Alejandro Sánchez Alvarado

2007-01-01

166

Defined Media for Stem Cell Culture.  

National Technical Information Service (NTIS)

Stem cells, including mammalian, and particularly primate primordial stem cells (pPSCs) such as human embryonic stem cells (hESCs), hold great promise for restoring cell, tissue, and organ function. However, cultivation of stem cells, particularly undiffe...

X. H. Parson E. Y. Snyder

2004-01-01

167

EFFECTS OF NEUROINFLAMMATION ON THE REGENERATIVE CAPACITY OF BRAIN STEM CELLS  

PubMed Central

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the LPS-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases.

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2012-01-01

168

Differential effects of cyclic uniaxial stretch on human mesenchymal stem cell into skeletal muscle cell.  

PubMed

Both fetal and adult skeletal muscle cells are continually being subjected to biomechanical forces. Biomechanical stimulation during cell growth affects proliferation, differentiation and maturation of skeletal muscle cells. Bone marrow-derived hMSCs [human MSCs (mesenchymal stem cells)] can differentiate into a variety of cell types, including skeletal muscle cells that are potentially a source for muscle regeneration. Our investigations involved a 10% cyclic uniaxial strain at 1 Hz being applied to hMSCs grown on collagen-coated silicon membranes with or without IGF-I (insulin-like growth factor-I) for 24 h. Results obtained from morphological studies confirmed the rearrangement of cells after loading. Comparison of MyoD and MyoG mRNA levels between test groups showed that mechanical loading alone can initiate myogenic differentiation. Furthermore, comparison of Myf5, MyoD, MyoG and Myf6 mRNA levels between test groups showed that a combination of mechanical loading and growth factor results in the highest expression of myogenic genes. These results indicate that cyclic strain may be useful in myogenic differentiation of stem cells, and can accelerate the differentiation of hMSCs into MSCs in the presence of growth factor. PMID:22681392

Haghighipour, Nooshin; Heidarian, Saeide; Shokrgozar, Mohammad Ali; Amirizadeh, Naser

2012-07-01

169

Role of stem-cell-derived microvesicles in the paracrine action of stem cells.  

PubMed

The paracrine theory has recently changed the view of the biological action of stem cells and of the subsequent potential application of stem cells in regenerative medicine. Indeed, most of the beneficial effects of stem-cell-based therapy have been attributed to soluble factors released from stem cells. In this context, MVs (microvesicles) released as exosomes from the endosomal compartment, or as shedding vesicles from the cell surface, may play a relevant role in the intercellular communication between stem and injured cells. By transferring proteins, bioactive lipids, mRNA and microRNA, MVs act as vehicles of information that may lead to alteration of the phenotype of recipient cells. The exchange of information between stem cells and tissue-injured cells is reciprocal. The MV-mediated transfer of tissue-specific information from the injured cells to stem cells may reprogramme the latter to gain phenotypic and functional characteristics of the cell of origin. On the other hand, MVs released from stem cells may confer a stem-cell-like phenotype to injured cells, with the consequent activation of self-regenerative programmes. In fact, MVs released from stem cells retain several biological activities that are able to reproduce the beneficial effects of stem cells in a variety of experimental models. PMID:23356298

Camussi, Giovanni; Deregibus, Maria Chiara; Cantaluppi, Vincenzo

2013-02-01

170

[Are satellite cells stem cells?].  

PubMed

Satellite cells, localized in the niche between the membrane of muscle fiber and basal lamina that surrounds it, serve as a source of myoblasts that are necessary for both growth and regeneration of skeletal muscle. Apart from their ability to convert into myoblasts, satellite cells are also able to self-renew, thus, they meet requirements for tissue specific, unipotent stem cells. Recently conducted research revealed that population of satellite cells is heterogeneous. The article summarizes current information on biology and characteristics of satellite cells, and also describes models concerning mechanisms of self-renewal and differentiation of satellite cells. Experiments regarding in vitro differentiation of satellite cells into other cell types are also discussed. Moreover, other population of stem cells localized in the muscle are described in this review. PMID:24044285

Archacka, Karolina; Kowalski, Kamil; Brzóska, Edyta

2013-01-01

171

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

Microsoft Academic Search

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

Kristopher Harry Morgan

2009-01-01

172

Framing Effects of News Coverage of the Embryonic Stem Cell Controversy: Issue Involvement as an Effects Moderator  

Microsoft Academic Search

This study examines reactions to ethical and strategic framing in the news coverage of the embryonic stem cell research controversy, depending on the level of issue involvement. In order to test hypotheses regarding the effects of strategic vs. ethical frames and the moderating role played by issue involvement, an online experiment was conducted. Results indicated that these two frames interacted

Doshik Yun; Seungahn Nah; Douglas M. McLeod

2008-01-01

173

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

SciTech Connect

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

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

2005-08-12

174

Controversies over stem cell research  

Microsoft Academic Search

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

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

2003-01-01

175

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

PubMed

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

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

2012-06-12

176

Stem cell therapy for diabetes  

PubMed Central

Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future.

Lee, KO; Gan, SU; Calne, RY

2012-01-01

177

Comparative effects of bone marrow mesenchymal stem cells on lipopolysaccharide-induced microglial activation.  

PubMed

After injury to the CNS, microglia are rapidly activated and concentrated and trigger inflammatory reaction at the sites of injury. Bone marrow mesenchymal stem cells (BMMSC) represent attractive cell sources for treating CNS injury. Although anti-inflammatory and paracrine effects of grafted BMMSC have been shown, direct modulation of BMMSC on microglia in situ remains unclear. The present work employs in vitro transwell assay to characterize the effects of BMMSC on LPS-stimulated microglia. BMMSC are cultivated in serum and serum-free (sf) conditions, namely, BMMSC and BMMSC-sf. Both cultures express major surface markers specific for mesenchymal stem cells. However, the BMMSC-sf exhibit sphere-like structure with reduced expression of two adherent cell markers, CD29 and CD90. Compared to BMMSC-sf, BMMSC are fibroblast like and have faster differentiation potential into neural-like cells. Furthermore, BMMSC release significant levels of TIMP-1 and VEGF, regardless of being alone or in coculture. The downregulated MMP-9 mRNA may be caused by TIMP-1 secretion from BMMSC. Our cell culture system provides a powerful tool for investigating the molecular and cellular changes in microglia-BMMSC cocultures. PMID:23589758

Tseng, Fan-Wei; Tsai, May-Jywan; Yu, Li-Yu; Fu, Yu-Show; Huang, Wen-Cheng; Cheng, Henrich

2013-03-24

178

The new stem cell biology.  

PubMed Central

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

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

2002-01-01

179

Pleiotropic Effects of Transforming Growth Factor-? in Hematopoietic Stem Cell Transplantation  

PubMed Central

Transforming growth factor ? (TGF?) is a pleiotropic cytokine with beneficial and detrimental effects post-hematopoietic stem cell transplantation (HSCT). TGF? is increased in specific sites post-engraftment and can suppress immune responses and maintain peripheral tolerance. Thus, TGF? may promote allograft acceptance. However, TGF? is also the central pathogenic cytokine in fibrotic disease and likely promotes pneumonitis. Although TGF? can enhance leukocyte recruitment and IgA production, it inhibits both innate and adaptive immune cell function and inhibits anti-viral host defense post-HSCT. This review will focus on the current understanding of TGF? biology and the numerous ways it can impact outcomes post-transplant.

Coomes, Stephanie M.; Moore, Bethany B.

2010-01-01

180

Stem cells today: B1. Bone marrow stem cells  

Microsoft Academic Search

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

RG Edwards

2004-01-01

181

Stem Cells and Bioactive Materials  

Microsoft Academic Search

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

Robert C. Bielby; Julia M. Polak

182

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

PubMed Central

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

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

2013-01-01

183

401. Engineering Retroviral Vectors for Stem Cell Therapies-Overcoming the Effect of Gene Silencing  

Microsoft Academic Search

The combined application of gene therapy and stem cell engineering for tissue regeneration have has drawn immense recent interest. In recent clinical trials with several patients who suffered from different forms of severe combined immunodeficiency syndrome (SCID), corrective genes were introduced into the patients' hematopoeitic stem cells via Moloney Murine Leukemia (MoMLV) viral vectors. This marked the first successful reports

Gary K. Lee; David V. Schaffer

2004-01-01

184

BD™ Stem Cell Enumeration Kit  

Center for Biologics Evaluation and Research (CBER)

... BD™ Stem Cell Enumeration Kit. Applicant: BD Biosciences. 510(k) number: BK110037. Product: BD™ Stem Cell Enumeration Kit. ... More results from www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts

185

Stem cells today: B1. Bone marrow stem cells.  

PubMed

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 on very recent studies. Methods of identifying, culturing, expanding and grafting stem cells are described, including the separation of haemopoietic and mesenchyme cell lines (HSC and MSC) and recent more detailed analyses using numerous CD and other markers to identify very small subsets of stem cells such as multipotent adult progenitor cells (MAPC) and bone marrow stromal stem cells (BMSSC) from MSC. Queries arising on the immense potential of these stem cell lines due to the discovery of epigentic factors and cell fusions influencing their development and potency are described. A section on cord blood stem cells is followed by a detailed discussion on the modern situation regarding the clinical use of stem cells, its recent setbacks due to epigenetic factors, different approaches to the discovery of a highly multipotent bone marrow stem cell, and a brief description of embryological approaches to identifying the basic bone marrow stem cell in very early mammalian embryos. PMID:15588475

Edwards, R G

2004-11-01

186

Breast Cancer Stem Cells  

PubMed Central

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.

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

2012-01-01

187

[Resident cardiac stem cells].  

PubMed

The search for sources of stem/progenitor cells the use of which has a potential to affect course of ischemic heart disease and chronic heart failure is conducted nowadays in many countries. Resident cardiac stem cells (CSC) were revealed during recent years on the basis of expression of c-kit, sca-1, MDR1, and islet-1 markers. In vitro experiments demonstrated possibility of their differentiation into cardiomyocytes, smooth muscle cell and endothelial cells. Introduction of CSC in injured myocardium in animals facilitated its partial repair and short term improvement of cardiac function. This holds promise for the use of these cells in the future. In the review we have attempted to summarize literature data on resident CSC and their application for the treatment of heart diseases. PMID:21623726

Dergilev, K V; Rubina, K A; Parfenova, E V

2011-01-01

188

Introduction to stem cell therapy.  

PubMed

Stem cells have the ability to differentiate into specific cell types. The 2 defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are 2 major classes of stem cells: pluripotent cells, which can become any cell in the adult body, and multipotent cells, which are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation, and therapeutic applications are discussed. Stem cells have great potential in tissue regeneration and repair, but much still needs to be learned about their biology, manipulation, and safety before their full therapeutic potential can be achieved. PMID:19242274

Biehl, Jesse K; Russell, Brenda

189

Effect of antibiotics against Mycoplasma sp. on human embryonic stem cells undifferentiated status, pluripotency, cell viability and growth.  

PubMed

Human embryonic stem cells (hESCs) are self-renewing pluripotent cells that can differentiate into specialized cells and hold great promise as models for human development and disease studies, cell-replacement therapies, drug discovery and in vitro cytotoxicity tests. The culture and differentiation of these cells are both complex and expensive, so it is essential to extreme aseptic conditions. hESCs are susceptible to Mycoplasma sp. infection, which is hard to detect and alters stem cell-associated properties. The purpose of this work was to evaluate the efficacy and cytotoxic effect of Plasmocin(TM) and ciprofloxacin (specific antibiotics used for Mycoplasma sp. eradication) on hESCs. Mycoplasma sp. infected HUES-5 884 (H5 884, stable hESCs H5-brachyury promoter-GFP line) cells were effectively cured with a 14 days Plasmocin(TM) 25 µg/ml treatment (curative treatment) while maintaining stemness characteristic features. Furthermore, cured H5 884 cells exhibit the same karyotype as the parental H5 line and expressed GFP, through up-regulation of brachyury promoter, at day 4 of differentiation onset. Moreover, H5 cells treated with ciprofloxacin 10 µg/ml for 14 days (mimic of curative treatment) and H5 and WA09 (H9) hESCs treated with Plasmocin(TM) 5 µg/ml (prophylactic treatment) for 5 passages retained hESCs features, as judged by the expression of stemness-related genes (TRA1-60, TRA1-81, SSEA-4, Oct-4, Nanog) at mRNA and protein levels. In addition, the presence of specific markers of the three germ layers (brachyury, Nkx2.5 and cTnT: mesoderm; AFP: endoderm; nestin and Pax-6: ectoderm) was verified in in vitro differentiated antibiotic-treated hESCs. In conclusion, we found that Plasmocin(TM) and ciprofloxacin do not affect hESCs stemness and pluripotency nor cell viability. However, curative treatments slightly diminished cell growth rate. This cytotoxic effect was reversible as cells regained normal growth rate upon antibiotic withdrawal. PMID:23936178

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

2013-07-30

190

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

PubMed Central

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

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

2013-01-01

191

[Effect of calusterone on the stem cell compartment after suppression with busulfan in mice].  

PubMed

These studies were undertaken to evaluate the effect of Calusterone (a weakly androgenic steroid) on hemopoiesis in mice. Cellular proliferation was suppressed by a single (IP) injection of busulfan (BU) (40 mg/Kg). Calusterone (CA) was administered s.c. SC daily (10 mg/Kg); controls received an equivalent injection of oil vehicle. Hemopoiesis was characterized by measurement of peripheral blood neutrophils, bone marrow cellularity, differentials and stem cell content. This included pluripotent (CFU-S), granulocytic (CFU-C) and erythroid (CFU-E) progenitor cells. Only a minimal decrease in narrow cellularity was observed after busulfan; similar values were obtained in calusterone recipients. Neutrophils fell by day 4, showed an abortive rise on day 8 and subsequently fell to 32% of control values. Calusterone recipients showed a 2 fold higher value (62%) on day 12. CFU-S, CFU-C, and CFU-E were depressed to 20-40% of control values by day 2 after busulfan. Although CFU-S and CFU-C remained depressed through the 14th day, CFU-E recovered by day 8 CA stimulated an overshoot in these cells to 288% of control values. These findings correlated with an increase in marrow erythroid cells to 182% on day 10. CFU-S remained low (20%) by day 14 and gradually increased to 50% of control by day 24. A delayed 10 day course of CA more than doubled the CFU-S recovery. These findings show that BU markedly suppress hemopoietic stem cells: a differential recovery is noted between CFU-E and the other progenitor cells. CA increase the recovery of all 3 hemopoietic stem cell compartments when given either immediately or in a delayed schedule. This suggests that this compound may be of use in the therapy of bone marrow hypoplasia. PMID:162174

Rizzoli, V; Porcellini, A; Manna, A; Shadduck, R K; Pigoli, G; Butturini, U

1979-01-01

192

Prospects of Stem Cell Transplantation in Autoimmune Diseases  

Microsoft Academic Search

Severe autoimmune diseases are not cured by current conventional treatments. Preclinical studies of treatments requiring stem cell transplantation have shown sustained remissions in some models of autoimmune diseases. Both autologous stem cell transplantation after high-dose immunoablative therapy and allogeneic stem cell transplantation have a profound effect on the recipient's immunological system. Pilot clinical studies of autologous stem cell transplantation are

Richard A. Nash

2000-01-01

193

Effects of bone marrow mesenchymal stem cells on cell proliferation and growth factor expression of limbal epithelial cells in vitro.  

PubMed

Mesenchymal stem cells (MSCs) can play an active role in there construction of the ocular surface; however, the mechanisms by which the implanted MSCs exert their effects remain elusive. In the present study, we investigated the influences of MSCs on cell proliferation and growth factor expression of corneal limbal epithelial cells (LECs) in vitro. Rat LECs were either cocultured with rat MSCs or cultured in rat MSC condition edmedium. The harvested LECs were subjected to light microscopy, MTT assay, bromodeoxyuridine (BrdU)staining, flow cytometry and real-time quantitative RT-PCR analysis, respectively. Light microscopy showed that coculturing of LECs with MSCs significantly increased the proliferation of LECs. The MTT assay showed that MSC-conditioned medium significantly increased the cell viability of LECs compared to those incubated with plain medium. BrdU immunostaining and flow-cytometric analysis of the cell cycle showed that the cell proliferation rate of LECs cocultured with MSCs was significantly higher than that of LECs cultured alone. Real-time quantitative RT-PCR analysis showed that expression of epidermal growth factor in LECs cocultured with MSCs was significantly higher than that in LECs cultured alone. However, expression of basic fibroblast growth factor showed no difference under the two culture conditions. These results indicate that MSCs promote the survival and proliferation of LECs, and these effects may be mediated ina paracrine manner. PMID:22473034

Hu, Nan; Zhang, Yuan-Yuan; Gu, Hong-Wei; Guan, Huai-Jin

2012-01-01

194

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

PubMed Central

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

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

2013-01-01

195

Contribution of stem cells to kidney repair.  

PubMed

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 cells recruited has not been determined. If endogenous bone marrow-derived stem cells repopulate injured nephrons directly or act indirectly over a paracrine/endocrine mechanism remains also controversial. Therapeutic administration of exogenous bone marrow derived stem cells in animal models of acute renal injury suggests that a stem cell-based therapy may improve the recovery of both glomerular and tubular compartments. Whereas the therapeutic benefit of sorted hematopoietic stem cells remains uncertain, several studies showed a beneficial effect of mesenchymal stem cell administration in models of acute tubular injury and of endothelial progenitors in acute glomerular injury. Recent studies demonstrate the presence of resident stem cells within the adult kidney. These cells are capable, when injected in animals with acute tubular injury, to localize to renal compartments and contribute to regeneration. This review summarizes the current literature on the physiological role of endogenous stem cells in renal regeneration and on the therapeutic potential of exogenous stem cell administration. Moreover, critical points that still need clarification, such as the homing mechanisms of stem cells to injured tissue, the secreted factors underlying the paracrine/endocrine mechanisms and the long-term behaviour of in vivo administered stem cells, are discussed. PMID:19149624

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

2009-01-01

196

Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure  

SciTech Connect

Long-term functional capacities of marrow cell lines were defined by competitive repopulation, a technique capable of detecting a small decline in repopulating abilities. There was little or no difference between cells from old and young donors, but a single serial transplantation caused a large decline in repopulating ability. Varying the numbers of marrow cells transplanted into the initial carrier from 10(5) to 10(7) did not alter the ability of the carrier's marrow cells to repopulate in competition with previously untransplanted cells. This ability was improved only in carriers that had received 10(8) marrow cells, although deleterious effects of transplantation were still present. These effects were not solely caused by cell damage from the transplantation procedure, because transplantation by parabiosis, or recovery from sublethal irradiation without transplantation, reduced repopulating abilities as much as transplanting 10(5) to 10(7) marrow cells. The transplantation effect also was not caused solely by irradiation, because the same effect appeared in unirradiated W/Wv carriers. The transplantation effect was more pronounced when donors were identified by hemoglobin type than by chromosome markers, implying that nonerythroid cell lines may be less affected by transplantation than erythroid precursor cells. When the effects of a lifetime of normal function and a single transplantation were compared, the latter caused 3-7 times more decline in repopulating abilities of phytohemagglutinin-responsive cell precursors, and at least 10-20 times more decline in erythroid cell precursors. Stem cell lines can be serially transplanted at least five times before losing their ability to repopulate and save lethally irradiated recipients or to cure genetically anemic mice. Therefore, if transplantation causes an acceleration of the normal aging process, these figures suggest that stem cells should be able to function normally through at least 15-50 life spans.

Harrison, D.E.; Astle, C.M.

1982-12-01

197

Stem Cell Interaction with Topography  

Microsoft Academic Search

\\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

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

198

Microtechnology for Stem Cell Culture  

Microsoft Academic Search

\\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

Elena Serena; Elisa Cimetta; Camilla Luni; Nicola Elvassore

199

Stem Cells in Immortal Hydra  

Microsoft Academic Search

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

Thomas C. G. Bosch

200

Aging of mesenchymal stem cell in vitro  

Microsoft Academic Search

BACKGROUND: A hot new topic in medical treatment is the use of mesenchymal stem cells (MSC) in therapy. The low frequency of this subpopulation of stem cells in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of long term culture on the senescence of these cells. RESULTS: The mean long term culture

Mohyeddin Mandana Bonab; Kamran Alimoghaddam; Fatemeh Talebian; Syed Hamid Ghaffari; Ardeshir Ghavamzadeh; Behrouz Nikbin

2006-01-01

201

Stem Cell Research  

Microsoft Academic Search

The case lays out the controversies surrounding stem cell research, looking specifically at therapeutic cloning and how the embryos produced in this process are produced solely to be destroyed. Thus, the dilemma of whether it is ethical to take one life to save another and the dilemma surrounding human cloning. This case may be used to portray problems in the

R. Freeman; Will Truslow; Pia Ahmad; Bidham Pamar

202

Miscreant myeloproliferative disorder stem cells  

Microsoft Academic Search

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

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

2008-01-01

203

Stem Cell Policy Exceptionalism: Proceed with Caution  

Microsoft Academic Search

The term “stem cell exceptionalism” has been used to characterize the policy response to controversies surrounding human embryonic\\u000a stem cell research. For example, governments and funding agencies have adopted policies governing the derivation and use of\\u000a human embryonic stem cell lines. These policies have effectively served to fill gaps in existing guidelines and regulations\\u000a and signal that scientists are committed

Geoffrey P. Lomax; Steven R. Peckman

204

Effect of sustained release of bone morphogenetic protein on osteogenic expression of mesenchymal stem cells.  

PubMed

The objective of this work was to investigate the effect of sustained release of rhBMP-2, grafted to biodegradable nanoparticles (NPs) based on osteogenic differentiation of bone mesenchymal stem (BMS) cells. The release kinetics of rhBM-2 was linear with incubation time in the first two weeks. rhBMP-2 grafted NPs were as effective in inducing mineralization as the rhBMP-2 directly added to the culture media. rhBMP-2 grafted NPs had much higher expression of osteogenic markers osteopontin (OP) and osteocalcin (OC), compared to the protein directly added to culture media. PMID:21096864

Jabbari, Esmaiel

2010-01-01

205

Stem cells and the Planarian Schmidtea mediterranea  

PubMed Central

In recent years, somatic stem cells have been heralded as potential therapeutic agents to address a large number of degenerative diseases. Yet, in order to rationally utilize these cells as effective therapeutic agents, and/or improve treatment of stem-cell-associated malignancies such as leukemias and carcinomas, a better understanding of the basic biological properties of stem cells needs to be acquired. A major limitation in the study of somatic stem cells lies in the difficulty of accessing and studying these cells in vivo. This barrier is further compounded by the limitations of in vitro culture systems, which are unable to emulate the microenvironments in which stem cells reside and which are known to provide critical regulatory signals for their proliferation and differentiation. Given the complexity of vertebrate adult somatic stem cell populations and their relative inaccessibility to in vivo molecular analyses, the study of somatic stem cells should benefit from analyzing their counterparts in simpler model organisms. In the past, the use of Drosophila or C. elegans has provided invaluable contributions to our understanding of genes and pathways involved in a variety of human diseases. However, stem cells in these organisms are mostly restricted to the gonads, and more importantly neither Drosophila, nor C. elegans are capable of regenerating body parts lost to injury. Therefore, a simple animal with experimentally accessible stem cells playing a role in tissue maintenance and/or regeneration should be very useful in identifying and functionally testing the mechanisms regulating stem cell activities. The planarian Schmidtea mediterranea is poised to fill this experimental gap. S. mediterranea displays robust regenerative properties driven by an adult, somatic stem cell population capable of producing the ?40 different cell types found in this organism, including the germ cells. Given that all known metazoans depend on stem cells for their survival, it is extremely likely that the molecular events regulating stem cell biology would have been conserved throughout evolution, and that the knowledge derived from studying planarian stem cells could be vertically integrated to the study of vertebrate somatic stem cells. Current efforts, therefore, are aimed at further characterizing the somatic population of planarian stem cells in order to define its suitability as a model system in which to mechanistically dissect the basic biological attributes of metazoans stem cells.

Sanchez Alvarado, Alejandro

2007-01-01

206

Biomaterials as Stem Cell Niche: Cardiovascular Stem Cells  

Microsoft Academic Search

\\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

Ge Zhang; Laura J. Suggs

207

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

PubMed

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

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

2010-10-01

208

Stem cells and the vasculature  

Microsoft Academic Search

Unraveling the contribution of stem and progenitor cells to blood vessel formation and, reciprocally, the importance of blood vessels to the production and function of stem and progenitor cells, has been a major focus of vascular research over the last decade, but has spawned many controversies. Here I review how vascular stem and progenitor cells contribute both vascular and nonvascular

Victoria L Bautch

2011-01-01

209

Notch Promotes Radioresistance of Glioma Stem Cells  

PubMed Central

Radiotherapy represents the most effective nonsurgical treatments for gliomas. Yet, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we showed that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) rendered the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhanced radiation-induced cell death and impaired clonogenic survival of glioma stem cells, but not non-stem glioma cells. Similarly, knockdown of Notch1 or Notch2 increased radiosensitivity of glioma stem cells. The specificity of the radiosensitizing effects of GSIs was confirmed by expression of the constitutively active intracellular domains of Notch1 or Notch2 that protected glioma stem cells against radiation. Notch inhibition with GSIs did not alter the DNA damage response of glioma stem cells following radiation, but rather impaired radiation-induced Akt activation and upregulated levels of the truncated apoptotic isoform of Mcl-1 (Mcl-1s). Taken together, our results suggest a critical role of Notch to promote radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment.

Wang, Jialiang; Wakeman, Timothy P.; Latha, Justin D.; Hjelmeland, Anita B.; Wang, Xiao-Fan; White, Rebekah R.; Rich, Jeremy N.; Sullenger, Bruce A.

2009-01-01

210

Normal Stem Cells and Cancer Stem Cells: The Niche Matters  

Microsoft Academic Search

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

Linheng Li; William B. Neaves

211

Melanocytes, melanocyte stem cells, and melanoma stem cells.  

PubMed

Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, and the latter play an active role in a lethal form of cancer. These 2 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 nontumor cells. PMID:23438380

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

212

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

PubMed

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

Pan, Fei; Chi, Lifeng; Schlatt, Stefan

2013-03-28

213

Stem Cell and Progenitor Cell Expansion.  

National Technical Information Service (NTIS)

The present invention provides compositions and methods for the expansion of stem cells and progenitor cells with adiponectin, adiponectin variants, or other molecules that activate adiponectin receptors and signaling, whereby the stem or progenitor cells...

L. DiMascio M. Uqoezwa Q. Wu T. Reya

2005-01-01

214

Cell fate determination from stem cells  

Microsoft Academic Search

In the adult, tissue-specific stem cells are thought to be responsible for the replacement of differentiated cells within continuously regenerating tissues, such as the liver, skin, and blood system. In this review, we will consider the factors that influence stem cell fate, taking as a primary example the cell fate determination of hematopoietic stem cells.

A J Wagers; J L Christensen; I L Weissman

2002-01-01

215

Stem cell therapy for human brain disorders.  

PubMed

Transplantation of stem cells or their derivatives, and mobilization of endogenous stem cells in the adult brain, have been proposed as future therapies for various brain disorders such as Parkinson's disease and stroke. In support, recent progress shows that neurons suitable for transplantation can be generated from stem cells in culture, and that the adult brain produces new neurons from its own stem cells in response to injury. However, from a clinical perspective, the development of stem cell-based therapies for brain diseases is still at an early stage. Many basic issues remain to be solved and we need to move forward with caution and avoid scientifically ill-founded trials in patients. We do not know the best stem cell source, and research on embryonic stem cells and stem cells from embryonic or adult brain or from other tissues should therefore be performed in parallel. We need to understand how to control stem cell proliferation and differentiation into specific cell types, induce their integration into neural networks, and optimize the functional recovery in animal models closely resembling the human disease. All these scientific efforts are clearly justified because, for the first time, there is now real hope that we in the future can offer patients with currently intractable diseases effective cell-based treatments to restore brain function. PMID:16221169

Lindvall, Olle; Kokaia, Zaal

2005-11-01

216

Gastric stem cells and gastric cancer stem cells  

PubMed Central

The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal evolution hypothesis, only cancer stem cells can initiate tumor formation, self-renew, and differentiate into various kinds of daughter cells. Because gastric cancer can originate from gastric stem cells and their self-renewal mechanism can be used by gastric cancer stem cells, we review here how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth factor, and bone morphogenetic protein signaling, may regulate the self-renewal and differentiation of gastric stem cells and gastric cancer stem cells. In addition, the precancerous change of the gastric epithelium and the status of isolating gastric cancer stem cells from patients are reviewed.

Han, Myoung-Eun

2013-01-01

217

Human cardiac stem cells  

PubMed Central

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

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

2007-01-01

218

Focus on Stem Cells Reprogramming somatic cells into stem cells  

Microsoft Academic Search

Recent scientific achievements in cell and developmental biology have provided unprecedented opportunities for advances in biomedical research. The demonstration that fully differentiated cells can reverse their gene expression profile to that of a pluripotent cell, and the successful derivation and culture of human embryonic stem cells (ESCs) have fuelled hopes for applications in regenerative medicine. These advances have been put

Ramiro Alberio; Keith H Campbell; Andrew D Johnson

219

Lung stem and progenitor cells.  

PubMed

Over the past few years, new insights have been added to the study of stem cells in the adult lung. The exploration of endogenous lung progenitors as well as the study of exogenously delivered stem cell populations holds promise for advancing our understanding of the biology of lung repair mechanisms. Moreover, it opens new possibilities for the use of stem cell therapy for the development of regenerative medicine approaches for the treatment of lung disease. Here, we discuss the main types of lung epithelial progenitor populations; the potential of endothelial progenitors, mesenchymal stem cells and embryonic stem cells for lung therapy, as well as summarize the cellular mechanisms involved. PMID:23406722

Ardhanareeswaran, Karthikeyan; Mirotsou, Maria

2013-02-11

220

Long-term adverse effects of hematopoietic stem cell transplantation on dental development in children  

Microsoft Academic Search

Purpose  The purpose of this study was to assess late effects of cytotoxic therapy with hematopoietic stem cell transplantation (HCT)\\u000a on dental development in survivors of childhood cancer.\\u000a \\u000a \\u000a \\u000a Materials and methods  Forty children who underwent allogeneic HCT for a variety of hematological malignancies were evaluated at a minimum of 2 years\\u000a after transplantation. We obtained information on oral symptoms, exposed panoramic radiographs (PRG),

I. G. M. van der Pas-van Voskuilen; J. S. J. Veerkamp; J. E. Raber-Durlacher; D. Bresters; A. J. van Wijk; A. Barasch; S. McNeal; R. A. Th. Gortzak

2009-01-01

221

Notch promotes radioresistance of glioma stem cells.  

PubMed

Radiotherapy represents the most effective nonsurgical treatments for gliomas. However, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we show that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) renders the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhance radiation-induced cell death and impair clonogenic survival of glioma stem cells but not non-stem glioma cells. Expression of the constitutively active intracellular domains of Notch1 or Notch2 protect glioma stem cells against radiation. Notch inhibition with GSIs does not alter the DNA damage response of glioma stem cells after radiation but rather reduces Akt activity and Mcl-1 levels. Finally, knockdown of Notch1 or Notch2 sensitizes glioma stem cells to radiation and impairs xenograft tumor formation. Taken together, our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment. PMID:19921751

Wang, Jialiang; Wakeman, Timothy P; Lathia, Justin D; Hjelmeland, Anita B; Wang, Xiao-Fan; White, Rebekah R; Rich, Jeremy N; Sullenger, Bruce A

2010-01-01

222

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

PubMed Central

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

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

2013-01-01

223

Effects of high glucose on mesenchymal stem cell proliferation and differentiation  

SciTech Connect

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.

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

224

Inhibitory Effects of Hypoxia on Metabolic Switch and Osteogenic Differentiation of Human Mesenchymal Stem Cells.  

PubMed

We previously demonstrated that metabolic switch and mitochondrial activation are required for osteogenic differentiation of human mesenchymal stem cells (hMSCs). However, stem cells in niches or transplanted into injured tissues constantly encounter hypoxic stress that hinders aerobic metabolism. Therefore, we investigated the effects of oxygen tension (1% vs. 21%) on metabolism and osteogenic differentiation of hMSCs. We found that hypoxia impaired osteogenic differentiation as indicated by attenuation of alkaline phosphatase (ALP) activity and expression of osteogenic markers Cbfa-1 and osteopontin. In addition, differentiation-induced mitochondrial activation was compromised as shown by the decrease in the expression of respiratory enzymes and oxygen consumption rate. On the contrary, anaerobic metabolism was augmented as revealed by the upregulation of glycolytic enzymes and increase of lactate production, rendering the cells to rely more on anaerobic glycolysis for energy supply. Moreover, administration of 2-deoxyglucose (a glycolytic inhibitor) but not antimycin A (a respiratory inhibitor) significantly decreased intracellular ATP levels of hMSCs differentiating under hypoxia. Treatment with cobalt chloride, a hypoxia-inducible factor-1? (HIF-1?) stabilizer, recapitulated the inhibitory effects of hypoxia, suggesting that HIF-1? is involved in the compromise of hMSCs differentiation. These results suggest that hypoxia inhibits metabolic switch and mitochondrial function and therefore suppresses osteogenic differentiation of hMSCs. PMID:23733376

Hsu, Shu-Han; Chen, Chien-Tsun; Wei, Yau-Huei

2013-06-01

225

Salivary gland cancer stem cells.  

PubMed

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

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

2013-06-28

226

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

PubMed

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

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

2013-01-16

227

Convergence of normal stem cell and cancer stem cell developmental stage: Implication for differential therapies  

PubMed Central

Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements. We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation. CSC can be the key to the elaboration of anti-cancer-based therapy. In this article, we focus on a controversial new theme relating to CSC. Tumorigenesis may have a critical stage characterized as a “therapeutic window”, which can be identified by association of molecular, biochemical and biological events. Identifying such a stage can allow the production of more effective therapies (e.g. manipulated stem cells) to treat several cancers. More importantly, confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against CSC. This conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem cells. Currently, there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of CSC. Studies on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of cancer. The crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (e.g. normal stem cells, CSC and embryonic stem cells). The differential studies of the convergence may result in novel therapies for treating cancers.

Li, Shengwen Calvin; Lee, Katherine L; Luo, Jane; Zhong, Jiang F; Loudon, William G

2011-01-01

228

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

PubMed

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

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

2013-04-13

229

Stem cell and precursor cell therapy  

Microsoft Academic Search

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

Jingli Cai; Mahendra S. Rao

2002-01-01

230

Mammary Stem Cells and Mammopoiesis  

Microsoft Academic Search

The isolation and characterization of mammary stem cells is fundamental to understanding mammary gland development and tissue homeostasis as well as breast oncogenesis. Recent studies have led to the prospective isolation of pluripotential stem cells from the mouse mammary gland through the identification of specific cell-surface markers and transplan- tation of cells into the mammary stromal microenvironment. A single cell

Jane E. Visvader; Geoffrey J. Lindeman

231

Immune Responses to Stem Cells and Cancer Stem Cells  

Microsoft Academic Search

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

Xiao-Feng Yang; Hong Wang

232

Decrease in hematopoietic stem cell domains as a delayed effect of x-irradiation  

SciTech Connect

Although the hematopoietic integrity of locally X-irradiated sites can be restored for a time even after fairly large doses, a secondary aplasia often occurs some months later. To gain further insight into this delayed effect within the framework of the stem cell regulatory domain hypothesis, we characterized the growth kinetics of spleen colony forming units (CFU-S) in WBB6FI-+/+ bone marrow transplanted into WBB6FI-W/WV mice in which one leg had been exposed to 10-30 Gy of X rays 4-5 months previously. Compared to unirradiated contralateral marrow, fewer CFU-S either reached the previously irradiated marrow or were seeded into sites that could support growth. The initial exponential growth of effectively seeded CFU-S was unchanged, but growth deceleration (inflection point) occurred at a lower level of CFU-S in marrow previously irradiated with 20-30 Gy. This change in the inflection point indicates a radiation dose-dependent decrease consistent with the decrease in bone marrow cellularity. The decrease in effective stem cell domains after 20 Gy was calculated to be about 35%. We interpret these results to reflect the highly localized nature of delayed radiation damage to the marrow microenvironment.

Maloney, M.A.; Lamela, R.A.; Patt, H.M.

1983-09-01

233

Spermatogonial Stem Cells  

Microsoft Academic Search

\\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

Dirk G. de Rooij

234

New perspectives in stem cell research: beyond embryonic stem cells.  

PubMed

Although stem cell research is a rather new field in modern medicine, media soon popularized it. The reason for this hype lies in the potential of stem cells to drastically increase quality of life through repairing aging and diseased organs. Nevertheless, the essence of stem cell research is to understand how tissues are maintained during adult life. In this article, we summarize the various types of stem cells and their differentiation potential in vivo and in vitro. We review current clinical applications of stem cells and highlight problems encountered when going from animal studies to clinical practice. Furthermore, we describe the current state of induced pluripotent stem cell technology and applications for disease modelling and cell replacement therapy. PMID:21481037

Leeb, C; Jurga, M; McGuckin, C; Forraz, N; Thallinger, C; Moriggl, R; Kenner, L

2011-04-01

235

Migratory properties of mesenchymal stem cells.  

PubMed

Mesenchymal stem cells raise great expectations in regenerative medicine due to their capacity to regenerate damaged tissues, thereby restoring organ tissue integrity and functionality. Even though it is not yet clear how mesenchymal stem cells are guided to injured tissue it is generally assumed that the directed migration of these cells is facilitated by the same soluble factors that also recruit immune competent cells to inflamed tissue areas. Tumor tissue represents another type of (chronically) inflamed tissue and because of that mesenchymal stem cells are highly attracted. Although some data indicate that esenchymal stem cells might have a beneficial effect on tumor growth due to anti-tumor effects the plethora of data suggest that tumor tissue recruited mesenchymal stem cells rather promote tumor growth and metastasis formation. Nonetheless, the enhanced tumor tropism of mesenchymal stem cells makes them ideal candidates for novel anti-cancer strategies. Like Trojan Horses genetically modified mesenchymal stem cells will deliver their deadly cargo, such as anti-tumor cytokines or oncolytic viruses, into cancerous tissues, thereby destroying the tumor form within. In this chapter we will summarize the current concepts of genetic modification of mesenchymal stem cells for future anti-cancer therapies. PMID:22899378

Dittmar, Thomas; Entschladen, Frank

2013-01-01

236

The Effects of Soluble Growth Factors on Embryonic Stem Cell Differentiation Inside of Fibrin Scaffolds  

PubMed Central

The goal of this research was to determine the effects of different growth factors on the survival and differentiation of murine embryonic stem cell derived neural progenitor cells (ESNPCs) seeded inside of fibrin scaffolds. Embryoid bodies (EBs) were cultured for 8 days in suspension, retinoic acid was applied for the final 4 days to induce ESNPC formation, and then the EBs were seeded inside of 3 dimensional (3D) fibrin scaffolds. Scaffolds were cultured in the presence of media containing different doses of the following growth factors: neurotrophin-3 (NT-3), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF-AA), ciliary neurotrophic factor (CNTF), and sonic hedgehog (Shh). The cell phenotypes were characterized using fluorescence activated cell sorting (FACS) and immunohistochemistry after 14 days of culture. Cell viability was also assessed at this time point. Shh (10 ng/mL) and NT-3 (25 ng/mL) produced the largest fractions of neurons and oligodendrocytes while PDGF (2 and 10 ng/mL) and bFGF (10 ng/mL) produced an increase in cell viability after 14 days of culture. Combinations of growth factors were tested based on the results of the individual growth factor studies to determine their effect on cell differentiation. The incorporation of ESNPCs and growth factors into fibrin scaffolds may serve as potential treatment for spinal cord injury (SCI).

Willerth, Stephanie M.; Faxel, Tracy E.; Gottlieb, David I.; Sakiyama-Elbert, Shelly E.

2008-01-01

237

Toxicity effects of methamphetamine on embryonic stem cell-derived neuron  

PubMed Central

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.

Meamar, Rokhsareh; Dehghani, Leila; Karamali, Freshte

2012-01-01

238

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

Microsoft Academic Search

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

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

2004-01-01

239

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

PubMed Central

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 has been previously described as involved in differentiation of preadipose cells and might be a potential therapeutic target to modulate proliferation and differentiation of adipocyte precursors. However, the impact of GSK3 inhibition on human adipose-derived stem cells remained to be investigated. The aim of this study was to investigate GSK3 as a possible target for pharmacological inhibition of stem cell adipogenesis. To reach this goal, we studied the effects of pharmacological inhibitors of GSK3, i.e. lithium chloride (LiCl) and BIO on proliferation and adipocyte differentiation of multipotent stem cells derived from human adipose tissue. Results Our results showed that GSK3 inhibitors inhibited proliferation and clonogenicity of human stem cells, strongly suggesting that GSK3 inhibitors could be potent regulators of the pool of adipocyte precursors in adipose tissue. The impact of GSK3 inhibition on differentiation of hMADS cells was also investigated. Adipogenic and osteogenic differentiations were inhibited upon hMADS treatment with BIO. Whereas a chronic treatment was required to inhibit osteogenesis, a treatment that was strictly restricted to the early step of differentiation was sufficient to inhibit adipogenesis. Conclusion These results demonstrated the feasibility of a pharmacological approach to regulate adipose-derived stem cell function and that GSK3 could represent a potential target for controlling adipocyte precursor pool under conditions where fat tissue formation is impaired.

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

2008-01-01

240

Modeling Stem Cell Induction Processes  

PubMed Central

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

Gracio, Filipe; Cabral, Joaquim; Tidor, Bruce

2013-01-01

241

Modeling stem cell induction processes.  

PubMed

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

Grácio, Filipe; Cabral, Joaquim; Tidor, Bruce

2013-05-08

242

Effects of topographical and mechanical property alterations induced by oxygen plasma modification on stem cell behavior.  

PubMed

Polymeric substrates intended for cell culture and tissue engineering are often surface-modified to facilitate cell attachment of most anchorage-dependent cell types. The modification alters the surface chemistry and possibly topography. However, scant attention has been paid to other surface property alterations. In studying oxygen plasma treatment of polydimethylsiloxane (PDMS), we show that oxygen plasma treatment alters the surface chemistry and, consequently, the topography and elasticity of PDMS at the nanoscale level. The elasticity factor has the predominant effect, compared with the chemical and topographical factors, on cell adhesions of human mesenchymal stem cells (hMSCs). The enhanced focal adhesions favor cell spreading and osteogenesis of hMSCs. Given the prevalent use of PDMS in biomedical device construction and cell culture experiments, this study highlights the importance of understanding how oxygen plasma treatment would impact subsequent cell-substrate interactions. It helps explain inconsistency in the literature and guides preparation of PDMS-based biomedical devices in the future. PMID:22970773

Yang, Yong; Kulangara, Karina; Lam, Ruby T S; Dharmawan, Rena; Leong, Kam W

2012-09-20

243

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

Microsoft Academic Search

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

Noriko Gotoh

2009-01-01

244

Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells in alloimmune response  

Microsoft Academic Search

Although both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) are known to have immunosuppressive effects, the mechanisms of immunosuppression are still controversial. Both types of stem cells suppressed not only the proliferation but also survival of CD4+ T cells in vitro. They suppressed secretion of various cytokines (IL-2, IL-12, IFN-?, TNF-?, IL-4, IL-5, IL-1?, and IL-10), whereas there

Kyu Hyun Han; Han Ro; Ju Ho Hong; Eun Mi Lee; Bumrae Cho; Hye Jung Yeom; Myung-Gyu Kim; Kook-Hwan Oh; Curie Ahn; Jaeseok Yang

2011-01-01

245

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

PubMed Central

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

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

2013-01-01

246

Stem cells—meet immunity  

Microsoft Academic Search

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

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

2009-01-01

247

Characteristics of glioma stem cells.  

PubMed

The cancer stem cell theory postulates that tumors are sustained by a select cell population with specific features, such as self-renewal ability and the capacity to give rise to a heterogeneous mass of tumor cells. The existence of such cells has been demonstrated for glioblastoma, with these cells being referred to as glioma stem cells (GSCs). Glioblastomas are notoriously heterogeneous tumors, however, and the isolation and characterization of their stem cells will require further investigations. Furthermore, the lack of unequivocal markers for GSCs and a partial overlap in characteristics with other cells often lead to confusion. Here, we review the characteristics necessary for a glioma cell to be considered a stem cell, and we adopt our murine glioblastoma model based on genetically modified neural stem cells to illustrate and discuss the GSC concept. PMID:23584571

Sampetrean, Oltea; Saya, Hideyuki

2013-04-13

248

Origins of pluripotent stem cells.  

PubMed

Different types of pluripotent stem cells can be identified and cultured in vitro. Here an overview is presented of the various pluripotent stem cells types. Embryonal carcinoma (EC) cells that have been cultured in vitro provided the groundwork for future pluripotent cell cultures. Conditions established for these cells such as culture on a feeder layer of mouse embryonic fibroblasts and the importance of fetal calf serum were initially also used for the culture of mouse embryonic stem (ES) cells derived from the inner cell masses of blastocysts. Embryonic stem cells derived from human blastocysts were found to require different conditions and are cultured in the presence of activin and basic fibroblast growth factor. Recently pluripotent stem cells have also been derived from mouse peri-implantation epiblasts. Since these epiblast stem cells (EpiSCs) require the same conditions as the human ES cells it has been suggested that human ES cells are more similar to mouse EpiSCs than to mouse ES cells. Pluripotent cell lines have also been derived from migratory primordial germ cells and spermatogonial stem cells. The creation of pluripotent stem cells from adult cells by the introduction of reprogramming transcription factors, so-called induced pluripotent stem (iPS) cells allowed the derivation of patient-specific pluripotent stem cells without the need of creation of a human blastocyst after cloning by somatic cells nuclear transfer. Recently it has become clear however that iPS cells may be quite different to ES cells in terms of epigenetics. PMID:21747344

Roelen, B A J; Chuva De Sousa Lopes, S M

2011-08-01

249

Stem cells in the eye  

Microsoft Academic Search

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

Mike Boulton; Julie Albon

2004-01-01

250

Photoinhibition of stem elongation by blue and red light. Effects on hydraulic and cell wall properties  

SciTech Connect

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

Kigel, J.; Cosgrove, D.J. (Hebrew Univ., Jerusalem (Israel) Pennsylvania State Univ., University Park (USA))

1991-04-01

251

Resident cardiac stem cells.  

PubMed

The introduction of stem cells in cardiology provides new tools in understanding the regenerative processes of the normal and pathologic heart and opens new options for the treatment of cardiovascular diseases. The feasibility of adult bone marrow autologous and allogenic cell therapy of ischemic cardiomyopathies has been demonstrated in humans. However, many unresolved questions remain to link experimental with clinical observations. The demonstration that the heart is a self-renewing organ and that its cell turnover is regulated by myocardial progenitor cells offers novel pathogenetic mechanisms underlying cardiac diseases and raises the possibility to regenerate the damaged heart. Indeed, cardiac stem progenitor cells (CSPCs) have recently been isolated from the human heart by several laboratories although differences in methodology and phenotypic profile have been described. The present review points to the potential role of CSPCs in the onset and development of congestive heart failure and its reversal by regenerative approaches aimed at the preservation and expansion of the resident pool of progenitors. PMID:22114897

Frati, C; Savi, M; Graiani, G; Lagrasta, C; Cavalli, S; Prezioso, L; Rossetti, P; Mangiaracina, C; Ferraro, F; Madeddu, D; Musso, E; Stilli, D; Rossini, A; Falco, A; Angelis, A De; Rossi, F; Urbanek, K; Leri, A; Kajstura, J; Anversa, P; Quaini, E; Quaini, F

2011-10-01

252

CD11c? cells partially mediate the renoprotective effect induced by bone marrow-derived mesenchymal stem cells.  

PubMed

Previous studies have shown that induction of immune tolerance by mesenchymal stem cells (MSCs) is partially mediated via monocytes or dendritic cells (DCs). The purpose of this study was to determine the role of CD11c? cells in MSC-induced effects on ischemia/reperfusion injury (IRI). IRI was induced in wildtype (WT) mice and CD11c?-depleted mice following pretreatment with or without MSCs. In the in-vitro experiments, the MSC-treated CD11c? cells acquired regulatory phenotype with increased intracellular IL-10 production. Although splenocytes cocultured with MSCs showed reduced T cell proliferation and expansion of CD4?FoxP3? regulatory T cells (Tregs), depletion of CD11c? cells was associated with partial loss of MSCs effect on T cells. In in-vivo experiment, MSCs' renoprotective effect was also associated with induction of more immature CD11c? cells and increased FoxP3 expression in I/R kidneys. However all these effects induced by the MSCs were partially abrogated when CD11c? cells were depleted in the CD11c?-DTR transgenic mice. In addition, the observation that adoptive transfer of WT CD11c? cells partially restored the beneficial effect of the MSCs, while transferring IL-10 deficient CD11c? cells did not, strongly suggest the important contribution of IL-10 producing CD11c? cells in attenuating kidney injury by MSCs. Our results suggest that the CD11c? cell-Tregs play critical role in mediating renoprotective effect of MSCs. PMID:23940814

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

2013-08-06

253

Effects of Wnt Signaling on Proliferation and Differentiation of Human Mesenchymal Stem Cells  

Microsoft Academic Search

Mesenchymal stem cells are pluripotent cells from bone marrow, which can be differentiated into the osteogenic, chondrogenic, and adipogenic lineages in vitro and are a source of cells in bone and cartilage tissue engineering. An improvement in current tissue-engineering protocols requires more detailed insight into the molecular cues that regulate the distinct steps of osteochondral differentiation. Because Wnt signaling has

Boer de Jan; Hong Jun Wang; Blitterswijk van Clemens

2004-01-01

254

Mimicking Stem Cell Niches to Increase Stem Cell Expansion  

PubMed Central

Summary Niches regulate lineage-specific stem cell self-renewal vs. differentiation in vivo and are comprised of supportive cells and extracellular matrix components arranged in a 3-dimensional topography of controlled stiffness in the presence of oxygen and growth factor gradients. Mimicking stem cell niches in a defined manner will facilitate production of the large numbers of stem cells needed to realize the promise of regenerative medicine and gene therapy. Progress has been made in mimicking components of the niche. Immobilizing cell-associated Notch ligands increased the self-renewal of hematopoietic (blood) stem cells. Culture on a fibrous scaffold that mimics basement membrane texture increased the expansion of hematopoietic and embryonic stem cells. Finally, researchers have created intricate patterns of cell-binding domains and complex oxygen gradients.

Dellatore, Shara M.; Garcia, A. Sofia; Miller, William M.

2008-01-01

255

Autophagic control of cell 'stemness'  

PubMed Central

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

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

2013-01-01

256

Stem cells for myocardial regeneration.  

PubMed

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

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

2002-12-13

257

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

PubMed

Regional HLA frequency differences are of potential relevance for the optimization of stem cell donor recruitment. We analyzed a very large sample (n?=?123,749) of registered Polish stem cell donors. Donor figures by 1-digit postal code regions ranged from n?=?5,243 (region 9) to n?=?19,661 (region 8). Simulations based on region-specific haplotype frequencies showed that donor recruitment in regions 0, 2, 3 and 4 (mainly located in the south-eastern part of Poland) resulted in an above-average increase of matching probabilities for Polish patients. Regions 1, 7, 8, 9 (mainly located in the northern part of Poland) showed an opposite behavior. However, HLA frequency differences between regions were generally small. A strong indication for regionally focused donor recruitment efforts can, therefore, not be derived from our analyses. Results of haplotype frequency estimations showed sample size effects even for sizes between n?5,000 and n?20,000. This observation deserves further attention as most published haplotype frequency estimations are based on much smaller samples. PMID:24069237

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

2013-09-12

258

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

PubMed Central

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

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

2013-01-01

259

Stem cell therapy for neonatal brain injury: perspectives and challenges.  

PubMed

Cerebral palsy is a major health problem caused by brain damage during pregnancy, delivery, or the immediate postnatal period. Perinatal stroke, intraventricular hemorrhage, and asphyxia are the most common causes of neonatal brain damage. Periventricular white matter damage (periventricular leukomalacia) is the predominant form in premature infants and the most common antecedent of cerebral palsy. Stem cell treatment has proven effective in restoring injured organs and tissues in animal models. The potential of stem cells for self-renewal and differentiation translates into substantial neuroprotection and neuroregeneration in the animal brain, with minimal risks of rejection and side effects. Stem cell treatments described to date have used neural stem cells, embryonic stem cells, mesenchymal stem cells, umbilical cord stem cells, and induced pluripotent stem cells. Most of these treatments are still experimental. In this review, we focus on the efficacy of stem cell therapy in animal models of cerebral palsy, and discuss potential implications for current and future clinical trials. PMID:22162055

Titomanlio, Luigi; Kavelaars, Annemieke; Dalous, Jeremie; Mani, Shyamala; El Ghouzzi, Vincent; Heijnen, Cobi; Baud, Olivier; Gressens, Pierre

2011-11-01

260

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

SciTech Connect

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

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

1996-06-01

261

Stem cell transplantation; Iranian experience.  

PubMed

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others. PMID:19111033

Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Alimogaddam, Kamran; Jahani, Mohammad; Mousavi, Seied Asadollah; Mousavi, Seyed Asadollah; Iravani, Masood; Bahar, Babak; Khodabandeh, Ali; Khatami, Farnaz; Ghaffari, Fatemeh; Jalali, Arash

2009-01-01

262

The effect of stem cell proliferation regulators demonstrated with an in vitro assay.  

PubMed

Spleen colony formation after transplantation of bone marrow cells into irradiated mice has been used as an assay for hematopoietic stem cells (CFU-S), but has serious limitations intrinsic to an in vivo assay. In this report we describe experiments using an in vitro clonogenic assay that is especially suitable for studies of stem cell regulation as defined growth factors and normal untreated bone marrow can be used. We have demonstrated that the colony-forming cells have proliferative properties in common with CFU-S and respond to specific proliferation regulators previously detected using the spleen colony assay. PMID:3291981

Pragnell, I B; Wright, E G; Lorimore, S A; Adam, J; Rosendaal, M; DeLamarter, J F; Freshney, M; Eckmann, L; Sproul, A; Wilkie, N

1988-07-01

263

Effects of bone marrow mesenchymal stem cell transplantation on light-damaged retina.  

PubMed

PURPOSE. To investigate the effects and possible mechanisms of rat bone marrow mesenchymal stem cell (BMSC) transplantation on the light-damaged retinal structure and the apoptosis of photoreceptors. METHODS. DAPI-labeled BMSCs were transplanted into the subretinal space of light-damaged Sprague-Dawley rats 10 days after exposure. BMSCs were cultivated with the supernatant of homogenized retina (SHR). RESULTS. The outer nuclear layer (ONL) contained significantly more cells and the percentage of apoptotic ONL cells was significantly reduced in the BMSC transplantation group than in the phosphate-buffered solution injection group or the light damage group. Most DAPI-labeled BMSCs expressed brain-derived neurotrophic factor (BDNF). There was elevated basic fibroblast growth factor (bFGF) and BDNF immunoreactivity in the retinas of the BMSC transplantation group compared with the light damage group. In vitro culture showed that 10% of BMSCs changed from fusiform shape to multipolar shape. A fraction of cells expressed MAP2 or glial fibrillary acidic protein, and some cells expressed bFGF or BDNF when cultivated with light-damaged SHR for 7 days. CONCLUSIONS. BMSC subretinal transplantation could inhibit photoreceptor apoptosis and slow down retinal damage in light-damaged eyes. BMSCs could express bFGF (in vitro) and BDNF (in vitro and in vivo), pointing to potential trophic and protective effects on light-damaged retinas. PMID:20207980

Zhang, Yu; Wang, Wei

2010-03-05

264

Effects of titanium nanoparticles on adhesion, migration, proliferation, and differentiation of mesenchymal stem cells  

PubMed Central

Background The purpose of this study was to investigate the influences of nanoscale wear particles derived from titanium/titanium alloy-based implants on integration of bone. Here we report the potential impact of titanium oxide (TiO2) nanoparticles on adhesion, migration, proliferation, and differentiation of mesenchymal stem cells (MSC) from the cellular level to the molecular level in the Wistar rat. Methods A series of TiO2 nanoparticles (14 nm, 108 nm, and 196 nm) were synthesized and characterized by scanning electron microscopy and transmission electron microscopy, respectively. Results The TiO2 nanoparticles had negative effects on cell viability, proliferation, and the cell cycle of MSC in a dose-dependent and size-dependent manner. Confocal laser scanning microscopy was used to investigate the effects of particle internalization on adhesion, spreading, and morphology of MSC. The integrity of the cell membrane, cytoskeleton, and vinculin of MSC were negatively influenced by large TiO2 nanoparticles. Conclusion The Transwell migration assay and a wound healing model suggested that TiO2 nanoparticles had a strong adverse impact on cell migration as particle size increased (P < 0.01). Furthermore, alkaline phosphatase, gene expression of osteocalcin (OC) and osteopontin (OPN), and mineralization measurements indicate that the size of the TiO2 nanoparticles negatively affected osteogenic differentiation of MSC.

Hou, Yanhua; Cai, Kaiyong; Li, Jinghua; Chen, Xiuyong; Lai, Min; Hu, Yan; Luo, Zhong; Ding, Xingwei; Xu, Dawei

2013-01-01

265

Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.  

PubMed

Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05 % atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05 % atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02 %) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03 % of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease. PMID:23563790

Yoshinaga, Toshihiro; Hashimoto, Eri; Ukai, Wataru; Ishii, Takao; Shirasaka, Tomohiro; Kigawa, Yoshiyasu; Tateno, Masaru; Kaneta, Hiroo; Watanabe, Kimihiko; Igarashi, Takeshi; Kobayashi, Seiju; Sohma, Hitoshi; Kato, Tadafumi; Saito, Toshikazu

2013-04-06

266

Stem cells in veterinary medicine  

Microsoft Academic Search

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

Lisa A Fortier; Alexander J Travis

2011-01-01

267

Stem cells: Implications for urology  

Microsoft Academic Search

Stem cells are characterized by their potential immortality and are capable of self-renewal and differentiation. Stem cells\\u000a are proposed to provide the potential to cure degenerative diseases and to give important clues regarding human development\\u000a and aging. However, stem cell research has evoked enthusiasm and passionate debate regarding the ethics of their use in medicine\\u000a and reproduction. In this article,

Kirk C. Lo; Shannon Whirledge; Dolores J. Lamb

2005-01-01

268

Stem cell transplants at childbirth.  

PubMed

Autologous transplantation of stem cells is a natural phenomenon at birth in mammals via the umbilical cord. Here, we discuss that a delay in the cord clamping may increase stem cell supply to the baby, thereby allowing an innate stem cell therapy that can render acute benefits in the case of neonatal disease, as well as long-term benefits against age-related diseases. PMID:20020331

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

2010-03-01

269

Stem Cells and Asymmetric Cell Division  

Microsoft Academic Search

\\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

Frank Hirth

270

Nanotopographical Control of Stem Cell Differentiation  

PubMed Central

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.

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

2010-01-01

271

Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells.  

PubMed

Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions, although intravenous alteplase-administration ameliorated outcomes of patients receiving the therapy within 3 h of onset. In this study, we explored the therapeutic effects of neural progenitor cells (NPC) upon middle cerebral artery occlusion (MCAO) model of rats with exploration of the differences between adult and embryonic NPCs in therapeutic effects. GFP-labeled adult or embryonic NPCs were transplanted for transient MCAO model of rats at 1h after reperfusion. Rats were examined behaviorally using limb placement test, rotarod test and cylinder test with neuroradiological assessment using magnetic resonance imaging (MRI). Consequently after euthanasia, rats were immunohistochemically investigated to explore graft survival and immune reaction. MRI of rats receiving NPCs revealed significant reduction of infarct volumes, compared to vehicle-treated rats with corresponding behavioral amelioration. The transplanted cells were surviving in rats receiving NPCs, although the number of embryonic NPCs was significantly higher than that of adult NPCs. Iba-1-positive inflammatory cells of rats receiving adult NPCs were prominent, compared to those receiving embryonic NPCs, which might be a rationale for the differences between rats receiving adult and embryonic NPCs in the number of surviving NPCs. On the contraries, adult NPCs surely demonstrated therapeutic effects with a few surviving cells, thus indicating that the therapeutic effects might be due to trophic/growth factor-secretion from transplanted NPCs, rather than replacement of damaged host neurons. Therapeutic effects of NPCs for MCAO model of rats were clarified in this study. Transplantation of NPCs will be a hopeful strategy for stroke patients, although further studies are required for the patient safety and underlying mechanisms. PMID:18703033

Takahashi, Kazuya; Yasuhara, Takao; Shingo, Tetsuro; Muraoka, Kenichiro; Kameda, Masahiro; Takeuchi, Akira; Yano, Akimasa; Kurozumi, Kazuhiko; Agari, Takashi; Miyoshi, Yasuyuki; Kinugasa, Kazushi; Date, Isao

2008-07-30

272

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

PubMed

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

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

2013-05-02

273

Stem Cell Glycolipids  

Microsoft Academic Search

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

Makoto Yanagisawa

274

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

PubMed Central

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

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

2012-01-01

275

Stem cells in gastroenterology and hepatology  

Microsoft Academic Search

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

Michael Quante; Timothy C. Wang

2009-01-01

276

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

PubMed

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

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

2005-08-19

277

The neuroprotective effect of bone marrow stem cells is not dependent on direct cell contact with hypoxic injured tissue.  

PubMed

Bone marrow stem cells (BMSCs) are able to confer beneficial effects after transplantation into animals with ischemic brain injuries. This effect is probably mainly caused by the release of trophic factors, though the possibility of dead neural cells being replaced by BMSCs cannot be excluded. The aim of this study was to determine whether the neuroprotective effects in question are dependent on direct cell-cell contacts between BMSCs and injured tissue. We therefore investigated that interplay in an in vitro model of hippocampal organotypic slice cultures (OHCs), in order to avoid the interference due to immunological rejection processes following transplantation in vivo. To perform ischemic injury in vitro, OHCs were made subject to oxygen-glucose deprivation (OGD). The possible direct or indirect neuroprotective effects induced by BMSCs were evaluated 24 h after injury by reference to two experimental paradigms using ischemic injured hippocampal slices: (i) cell transplantation on the top of OGD-treated OHC, (ii) co-cultivation of cell culture with OHC space separated for 24 h. In both paradigms, the BMSC treatment induced comparable and significant neuroprotection in OGD-injured OHCs. This effect increased after treatment with serum-deprived BMSCs, enriched with cells expressing nestin and GFAP. Comparing cell transplantation and cell co-cultivation with injured tissue, we concluded that the neuroprotective effect of BMSCs evoked shortly after ischemia (24 h) does not depend on cell-cell contacts. Additionally OGD-treated OHC was found to stimulate co-cultured BMSCs into expressing higher levels of bFGF and NGF. Finally, ischemic hippocampal slices increased the expression of nestin and GFAP in co-cultivated BMSCs, as well as changing their morphology. PMID:19063882

Sarnowska, Anna; Braun, Holger; Sauerzweig, Steven; Reymann, Klaus G

2008-11-13

278

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

PubMed Central

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

Bart, Thomas

2010-01-01

279

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

PubMed

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

Conboy, Irina M; Rando, Thomas A

2012-06-15

280

Tracking transplanted bone marrow stem cells and their effects in the rat MCAO stroke model.  

PubMed

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

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

2013-03-29

281

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

PubMed Central

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.

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

2013-01-01

282

Stem cell leukemia protein directs hematopoietic stem cell fate  

Microsoft Academic Search

Stem cell leukemia (SCL) protein has been shown to be an essential transcription factor during hematopoietic development in the embryo. In adult hematopoiesis, however, the role for SCL has remained largely unknown, whereas it is expressed in bone marrow hematopoietic stem cells (HSCs). In this study, we performed HSC transplantation and an in vitro HSC differen- tiation assay using retrovirally

Atsushi Kunisato; Shigeru Chiba; Toshiki Saito; Keiki Kumano; Etsuko Nakagami-Yamaguchi; Tomoyuki Yamaguchi; Hisamaru Hirai

2004-01-01

283

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

Microsoft Academic Search

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

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

2006-01-01

284

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

Microsoft Academic Search

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

Kyung-Hwan Hyun; Chang-Hwan Yoon; Rae-Kwon Kim; Eun-Jung Lim; Sungkwan An; Myung-Jin Park; Jin-Won Hyun; Yongjoon Suh; Min-Jung Kim; Su-Jae Lee

2011-01-01

285

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

Microsoft Academic Search

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

Ti-Fei Yuan; Oscar Arias-Carrión

2008-01-01

286

Trophoblast stem cells.  

PubMed

Trophoblast stem cells (TSC) are the precursors of the differentiated cells of the placenta. In the mouse, TSC can be derived from outgrowths of either blastocyst polar trophectoderm (TE) or extraembryonic ectoderm (ExE), which originates from polar TE after implantation. The mouse TSC niche appears to be located within the ExE adjacent to the epiblast, on which it depends for essential growth factors, but whether this cellular architecture is the same in other species remains to be determined. Mouse TSC self-renewal can be sustained by culture on mitotically inactivated feeder cells, which provide one or more factors related to the NODAL pathway, and a medium supplemented with FGF4, heparin, and fetal bovine serum. Repression of the gene network that maintains pluripotency and emergence of the transcription factor pathways that specify a trophoblast (TR) fate enables TSC derivation in vitro and placental formation in vivo. Disrupting the pluripotent network of embryonic stem cells (ESC) causes them to default to a TR ground state. Pluripotent cells that have acquired sublethal chromosomal alterations may be sequestered into TR for similar reasons. The transition from ESC to TSC, which appears to be unidirectional, reveals important aspects of initial fate decisions in mice. TSC have yet to be derived from domestic species in which remarkable TR growth precedes embryogenesis. Recent derivation of TSC from blastocysts of the rhesus monkey suggests that isolation of the human equivalents may be possible and will reveal the extent to which mechanisms uncovered by using animal models are true in our own species. PMID:21106963

Roberts, R Michael; Fisher, Susan J

2010-11-24

287

The effects of nanophase ceramic materials on select functions of human mesenchymal stem cells  

NASA Astrophysics Data System (ADS)

Modification of the chemistry and surface topography of nanophase ceramics can provide biomaterial formulations capable of directing the functions of adherent cells. This effect relies on the type, amount, and conformation of adsorbed proteins that mediate the adhesion of mesenchymally-descended lineages. The mechanisms driving this response are not yet well-understood and have not been investigated for human mesenchymal stem cells (HMSCs), a progenitor-lineage critical to orthopaedic biomaterials. The present study addressed these needs by examining the in vitro adhesion, proliferation, and osteogenic differentiation of HMSCs as a function of substrate chemistry and grain size, with particular attention to the protein-mediated mechanisms of cell adhesion. Alumina, titania, and hydroxyapatite substrates were prepared with 1500, 200, 50, and 24 (alumina only) nm grain sizes, and characterized with respect to surface properties, porosity, composition, and phase. Adhesion of HMSCs was dependent upon both chemistry and grain size. Specifically, adhesion on alumina and hydroxyapatite was reduced on 50 and 24 (alumina only) nm surfaces, as compared to 1500 and 200 nm surfaces, while adhesion on titania substrates was independent of grain size. Investigation into the protein-mediated mechanisms of this response identified vitronectin as the dominant adhesive protein, demonstrated random protein distribution across the substrate surface without aggregation or segregation, and confirmed the importance of the type, amount, and conformation of adsorbed proteins in cell adhesion. Minimal cell proliferation was observed on 50 and 24 (alumina only) nm substrates of any chemistry. Furthermore, cell proliferation was up-regulated on 200 nm substrates after 7 days of culture. Osteogenic differentiation was not detected on 50 nm substrates throughout the 28 day culture period. In contrast, osteogenic differentiation was strongly enhanced on 200 nm substrates, occurring approximately 7 days earlier and in greater magnitude than that observed on 1500 nm substrates. In summary, the current study elucidated the chemical and topographical cues necessary to optimize the vitronectin-mediated adhesion, proliferation, and differentiation of human mesenchymal stem cells on ceramic surfaces. These results expand the understanding of surface-mediated cell functions and provide information pertinent to the design of next-generation orthopaedic and tissue engineering biomaterials.

Dulgar-Tulloch, Aaron Joseph

288

Use of 5Fluorouracil to Analyze the Effect of Macrophage Inflammatory Protein-la on Long-Term Reconstituting Stem Cells In Vivo  

Microsoft Academic Search

A macrophage-derived inhibitor of early hematopoietic pro- genitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage in- flammatory protein-la (MIP-1 a). We investigated the effect of MIP-1 a on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow re- population assay. Because long-term reconstituting (LTR) stem cells are

Valerie F. J. Quesniaux; Gerry J. Graham; Ian Pragnell; Deborah Donaldson; Stephen D. Wolpe; Norman N. Iscove; Barbara Fagg

289

Harvard Stem Cell Institute  

NSDL National Science Digital Library

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

290

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

PubMed Central

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

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

2012-01-01

291

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

NASA Astrophysics Data System (ADS)

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

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

292

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

PubMed Central

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

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

2013-01-01

293

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

PubMed Central

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

2013-01-01

294

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

PubMed

Multipotent adult stem cells have many potential therapeutic applications. Our recent findings suggest that hair follicles are a promising source of easily accessible multipotent stem cells. Stem cells in the hair follicle area express the neural stem cell marker nestin, suggesting that hair-follicle stem cells and neural stem cells have common features. Nestin-expressing hair follicle stem cells can form neurons and other cell types, and thus adult hair follicle stem cells could have important therapeutic applications, particularly for neurologic diseases. Transplanted hair follicle stem cells promote the functional recovery of injured peripheral nerve and spinal cord. Recent findings suggest that direct transplantation of hair-follicle stem cells without culture can promote nerve repair, which makes them potentially clinically practical. Human hair follicle stem cells as well as mouse hair follicle stem cells promote nerve repair and can be applied to test the hypothesis that human hair follicle stem cells can provide a readily available source of neurologically therapeutic stem cells. The use of hair follicle stem cells for nerve regeneration overcomes critical problems of embryonic stem cells or induced pluripotent stem cells in that the hair follicle stem cells are multipotent, readily accessible, non-oncogenic, and are not associated with ethical issues. PMID:21036545

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

2010-10-01

295

Breast cancer stem cells.  

PubMed

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

Owens, Thomas W; Naylor, Matthew J

2013-08-27

296

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

PubMed Central

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

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

2012-01-01

297

Stem Cells behind the Barrier  

PubMed Central

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.

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

2013-01-01

298

Bioprinting for stem cell research.  

PubMed

Recently, there has been growing interest in applying 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 biomolecules 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 cells 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

Tasoglu, Savas; Demirci, Utkan

2012-12-19

299

Mesenchymal stem cells: promising for myocardial regeneration?  

PubMed

The pandemic of cardiovascular disease is continuously expanding as the result of changing life styles and diets throughout the Old and New World. Immediate intervention therapy saves the lives of many patients after acute myocardial infarction (MI). However, for many this comes at the price of adverse cardiac remodeling and heart failure. Currently, no conventional therapy can prevent the negative aftermath of MI and alternative treatments are warranted. Therefore, cardiac stem cell therapy has been put forward over the past decade, albeit with modest successes. Mesenchymal Stem Cells (MSC) are promising because these are genuine cellular factories of a host of secreted therapeutic factors. MSC are obtained from bone marrow or adipose tissue (ADSC). However, the heart itself also contains mesenchymal- like stem cells, though more difficult to acquire than ADSC. Interestingly, mesenchymal cells such as fibroblasts can be directly or indirectly reprogrammed to all myocardial cell types that require replacement after MI. To date, the paracrine and juxtacrine mechanisms of ADSC and other MSC on vessel formation are best understood. The preconditioning of, otherwise naive, stem cells is gaining more interest: previously presumed deleterious stimuli such as hypoxia and inflammation, i.e. causes of myocardial damage, have the opposite effect on mesenchymal stem cells. MSC gain a higher therapeutic capacity under hypoxia and inflammatory conditions. In this review, mesenchymal stem cells and their working mechanisms are put into the perspective of clinical cardiac stem cell therapy. PMID:23547963

Przybyt, Ewa; Harmsen, Martin C

2013-07-01

300

Adult Stem and Progenitor Cells  

NASA Astrophysics Data System (ADS)

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

Geraerts, Martine; Verfaillie, Catherine M.

301

[Stem cell therapy: an update].  

PubMed

Medicine will be faced with a major challenge in coming years, namely how to treat for tissue dysfunction due to disease and aging There are two basic options: drug therapy and cell therapy. Stem cells have been the subject of intense speculation and controversy for several years, as they open up radically new therapeutic possibilities. Classical drugs can only smoothen consequences of tissue dysfunction, whereas cell therapy has the potential to restore tissue function by providing fresh cells. Cell therapy is totally different from organ transplantation, which can only benefit a limited number of patients. The use of the generic term "stem cells" to designate a whole variety of cell types that are present throughout life, is a source of confusion and ambiguity. It will take years of cognitive research to unravel the molecular mechanisms that govern a stem cell's multi- or totipotent status before we can fully exploit this therapeutic tool to the full. The younger a stem cell the greater its potential and, probably, the more durable its benefits, but the use of embryonic stem cells raises ethical issues. The redundancy or equivalence of diferent categories of cells is another source of controversy, yet researchers must be able to study stem cells in all their diversity, as complementary rather than competitive alternatives, in an acceptable ethical and regulatory environment. We briefly describe the three types of stem cells: pluripotent embryonic stem cells, fetal and adult stem cells, and pluripotent reprogrammed adult somatic cells. Only the former two categories have physiological functions: the first gives rise to tissues and organs while the second maintains tissue function during adulthood PMID:19883007

Coulombel, Laure

2009-03-01

302

History of Cancer Stem Cells  

Microsoft Academic Search

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

Stewart Sell

303

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

Microsoft Academic Search

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

Samane Ghazanfari; Mohammad Tafazzoli-Shadpour; Mohammad Ali Shokrgozar

2009-01-01

304

The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function.  

PubMed

The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine. PMID:23212100

Takehara, Yuji; Yabuuchi, Akiko; Ezoe, Kenji; Kuroda, Tomoko; Yamadera, Rie; Sano, Chiaki; Murata, Nana; Aida, Takuya; Nakama, Ken; Aono, Fumihito; Aoyama, Naoki; Kato, Keiich; Kato, Osamu

2012-11-19

305

The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function  

PubMed Central

The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine.

Takehara, Yuji; Yabuuchi, Akiko; Ezoe, Kenji; Kuroda, Tomoko; Yamadera, Rie; Sano, Chiaki; Murata, Nana; Aida, Takuya; Nakama, Ken; Aono, Fumihito; Aoyama, Naoki; Kato, Keiich; Kato, Osamu

2013-01-01

306

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

PubMed

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

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

2013-10-21

307

[Stem cell properties of therapeutic potential].  

PubMed

Stem cell research is a innovative technology that focuses on using undifferentiated cells able to self-renew through the asymmetrical or symmetrical divisions. Three types of stem cells have been studied in laboratory including embryonic stem cell, adult stem cells and induced pluripotent stem cells. Embryonic stem cells are pluripotent stem cells derived from the inner cell mass and it can give rise to any fetal or adult cell type. Adult stem cells are multipotent, have the ability to differentiate into a limited number of specialized cell types, and have been obtained from the bone marrow, umbilical cord blood, placenta and adipose tissue. Stem cell therapy is the most promising therapy for several degenerative and devastating diseases including digestive tract disease such as liver failure, inflammatory bowel disease, Celiac sprue, and pancreatitis. Further understanding of biological properties of stem cells will lead to safe and successful stem cell therapies. (Korean J Gastroenterol 2011;58: 125-132). PMID:21960099

Seo, Geom Seog

2011-09-25

308

Neuroprotective effect of a cell-free extract derived from human adipose stem cells in experimental stroke models.  

PubMed

A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke. PMID:23376682

Jeon, Daejong; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Ban, Jae-Jun; Park, Dong-Kyu; Yoon, Hye-Jin; Jung, Seungmoon; Yang, Hyunwoo; Kim, Byung Sun; Choi, Ji Ye; Kim, So Hee; Kim, Jeong-Min; Won, Chong-Hyun; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu

2013-01-30

309

Flexibility of Neural Stem Cells  

PubMed Central

Embryonic cortical neural stem cells are self-renewing progenitors that can differentiate into neurons and glia. We generated neurospheres from the developing cerebral cortex using a mouse genetic model that allows for lineage selection and found that the self-renewing neural stem cells are restricted to Sox2 expressing cells. Under normal conditions, embryonic cortical neurospheres are heterogeneous with regard to Sox2 expression and contain astrocytes, neural stem cells, and neural progenitor cells sufficiently plastic to give rise to neural crest cells when transplanted into the hindbrain of E1.5 chick and E8 mouse embryos. However, when neurospheres are maintained under lineage selection, such that all cells express Sox2, neural stem cells maintain their Pax6+ cortical radial glia identity and exhibit a more restricted fate in vitro and after transplantation. These data demonstrate that Sox2 preserves the cortical identity and regulates the plasticity of self-renewing Pax6+ radial glia cells.

Remboutsika, Eumorphia; Elkouris, Maximilianos; Iulianella, Angelo; Andoniadou, Cynthia L.; Poulou, Maria; Mitsiadis, Thimios A.; Trainor, Paul A.; Lovell-Badge, Robin

2011-01-01

310

Sex and stem cell research  

Microsoft Academic Search

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

John Fielder

2006-01-01

311

Effect of low dose bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells.  

PubMed

It has been previously reported that bisphenol A (BPA) can disturb the development of mammary structure and increase the risk of breast cancer in experimental animals. In this study, an in vitro model of human embryonic stem cell (hESC) differentiation into mammary epithelial cells was applied to investigate the effect of low dose BPA on the early stages of mammogenesis. A newly established hESC line was directionally differentiated into mammary epithelial cells by a well-established three-dimensional (3D) culture system. The differentiated mammary epithelial cells were characterized by immunofluorescence and western blotting assay, and were called induced differentiated mammary epithelial cells (iDMECs) based on these data. The hESCs were treated with low doses of BPA range 10(-9)-10(-6)M during the differentiation process, with DMSO as the solvent control and 17-?-estrodiol (E2) as the estrogen-positive control. Our results showed that low dose BPA and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein. Taken together, this study provides some insights into the effects of low dose BPA on the early differentiation stage of mammary epithelial cells and suggests an easier canceration status of iDMECs under the effect of low dose BPA during its early differentiation stage. PMID:23391485

Yang, Linqing; Luo, Lingfeng; Ji, Weidong; Gong, Chunmei; Wu, Desheng; Huang, Haiyan; Liu, Qingcheng; Xia, Bo; Hu, Gonghua; Zhang, Wenjuan; Zhang, Qian; Liu, Jianjun; Zhang, Wenchang; Zhuang, Zhixiong

2013-02-04

312

Direct and indirect effects of microstructured titanium substrates on the induction of mesenchymal stem cell differentiation towards the osteoblast lineage  

Microsoft Academic Search

Microstructured and high surface energy titanium substrates increase osseointegration in vivo. In vitro, osteoblast differentiation is increased, but effects of the surface directly on multipotent mesenchymal stem cells (MSCs) and consequences for MSCs in the peri-implant environment are not known. We evaluated responses of human MSCs to substrate surface properties and examined the underlying mechanisms involved. MSCs exhibited osteoblast characteristics

Rene Olivares-Navarrete; Sharon L. Hyzy; Daphne L. Hutton; Christopher P. Erdman; Marco Wieland; Barbara D. Boyan; Zvi Schwartz

2010-01-01

313

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

Microsoft Academic Search

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

Mohamadreza Baghaban Eslaminejad; Mahmood Talkhabi; Bahman Zeynali

2008-01-01

314

Strategies to Rescue Mesenchymal Stem Cells (MSCs) and Dental Pulp Stem Cells (DPSCs) from NK Cell Mediated Cytotoxicity  

PubMed Central

Background The aim of this paper is to study the function of allogeneic and autologous NK cells against Dental Pulp Stem Cells (DPSCs) and Mesenchymal Stem Cells (MSCs) and to determine the function of NK cells in a three way interaction with monocytes and stem cells. Methodology/Principal Findings We demonstrate here that freshly isolated untreated or IL-2 treated NK cells are potent inducers of cell death in DPSCs and MSCs, and that anti-CD16 antibody which induces functional split anergy and apoptosis in NK cells inhibits NK cell mediated lysis of DPSCs and MSCs. Monocytes co-cultured with either DPSCs or MSCs decrease lysis of stem cells by untreated or IL-2 treated NK cells. Monocytes also prevent NK cell apoptosis thereby raising the overall survival and function of NK cells, DPSCs or MSCs. Both total population of monocytes and those depleted of CD16+ subsets were able to prevent NK cell mediated lysis of MSCs and DPSCs, and to trigger an increased secretion of IFN-? by IL-2 treated NK cells. Protection of stem cells from NK cell mediated lysis was also seen when monocytes were sorted out from stem cells before they were added to NK cells. However, this effect was not specific to monocytes since the addition of T and B cells to stem cells also protected stem cells from NK cell mediated lysis. NK cells were found to lyse monocytes, as well as T and B cells. Conclusion/Significance By increasing the release of IFN-? and decreasing the cytotoxic function of NK cells monocytes are able to shield stem cells from killing by the NK cells, resulting in an increased protection and differentiation of stem cells. More importantly studies reported in this paper indicate that anti-CD16 antibody can be used to prevent NK cell induced rejection of stem cells.

Jewett, Anahid; Arasteh, Aida; Tseng, Han-Ching; Behel, Armin; Arasteh, Hobie; Yang, Wendy; Cacalano, Nicholas A.; Paranjpe, Avina

2010-01-01

315

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

Microsoft Academic Search

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

Yen Choo

316

Investigation of the Effect of Mechanical Strain on the Osteogenic Differentiation of Mesenchymal Stem Cells  

Microsoft Academic Search

\\u000a The engineering of functional bone constructs ex vivo is a rapidly growing branch in the field of tissue engineering. Bone\\u000a constructs generally comprise cells and a scaffold providing a supportive framework for the cells to grow as well as mechanical\\u000a stability. Furthermore, mechanical stimulation has become a substantial tool in functional tissue engineering.\\u000a \\u000a \\u000a Mesenchymal stem cells are a widely used

Solvig Diederichs; Daniel Riechers; Friederike Sempf; Susanne Kall; Cornelia Kasper; Martijn Griensven; Thomas Scheper

317

Scaffold effects on osteogenic differentiation of equine mesenchymal stem cells: an in vitro comparative study.  

PubMed

The in vitro viability, osteogenic differentiation, and mineralization of four different equine mesenchymal stem cells (MSCs) from bone marrow, periosteum, muscle, and adipose tissue are compared, when they are cultured with different collagen-based scaffolds or with fibrin glue. The results indicate that bone marrow cells are the best source of MSCs for osteogenic differentiation, and that an electrochemically aggregated collagen gives the highest cell viability and best osteogenic differentiation among the four kinds of scaffolds studied. PMID:23335515

Nino-Fong, Rodolfo; McDuffee, Laurie A; Esparza Gonzalez, Blanca P; Kumar, M Ramesh; Merschrod S, Erika F; Poduska, Kristin M

2013-01-18

318

Effects of Murine and Human Bone Marrow-Derived Mesenchymal Stem Cells on Cuprizone Induced Demyelination  

PubMed Central

For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.

Gudi, Viktoria; Hoffmann, Andrea; Salinas Tejedor, Laura; Janssen, Stefanie; Prajeeth, Chittappen Kandiyil; Baumgartner, Wolfgang; Kavelaars, Annemieke; Heijnen, Cobi J.; van Velthoven, Cindy; Hansmann, Florian; Skripuletz, Thomas; Stangel, Martin

2013-01-01

319

Cancer stem cell subsets and their relationships  

Microsoft Academic Search

Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of\\u000a cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be\\u000a appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells,\\u000a migrating cancer stem cells

Hai-Guang Liu; Chong Chen; Han Yang; Yi-Fei Pan; Xiao-Hua Zhang

2011-01-01

320

Differential Effects of a Stem Cell Factor-Immunoglobulin Fusion Protein on Malignant and Normal Hematopoietic Cells1  

Microsoft Academic Search

We genetically connected the extracellular domain of human stem cell factor to the Fc-portion of human IgG1. The chimeric recombinant stem cell factor IgG1 fusion protein (rSCF-IgG1) had an apparent ;Mr 190,000 and consisted of three identical covalently linked subunits. It specifically bound to c-kit and the high affinity Fcg receptor, respectively. Liquid phase rSCF-IgG1 was, on a molar basis,

Ulrike Erben; Eckhard Thiel; Michael Notter

1999-01-01

321

Effects of low frequency electromagnetic field on proliferation of human epidermal stem cells: An in vitro study.  

PubMed

To investigate the effects of low frequency electromagnetic fields (EMF) on the proliferation of epidermal stem cells, human epidermal stem cells (hESC) were isolated, expanded ex vivo, and then exposed to a low frequency EMF. The test and control cells were placed under the same environment. The test cells were exposed for 30?min/day to a 5?mT low frequency EMF at 1, 10, and 50?Hz for 3, 5, or 7 days. The effects of low frequency EMF on cell proliferation, cell cycle, and cell-surface antigen phenotype were investigated. Low frequency EMF significantly enhanced the proliferation of hESC in the culture medium in a frequency-dependent manner, with the highest cell proliferation rate at 50?Hz (P?cells at the S phase of the cell cycle, coupled with a decrease in the percentage of cells in the G1 phase (P?effect was not frequency dependent. The percentage of CD29(+) /CD71(-) cells remained unchanged in the low frequency EMF-exposed hESC. The results suggested that low frequency EMF influenced hESC proliferation in vitro, and this effect was related to the increased proportion of cells at the S phase. PMID:22926783

Zhang, Mingsheng; Li, Xinping; Bai, Liming; Uchida, Kenzo; Bai, Wenfang; Wu, Bo; Xu, Weicheng; Zhu, Hongxiang; Huang, Hong

2012-08-24

322

Lasers, stem cells, and COPD  

PubMed Central

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

2010-01-01

323

Stem Cells for Cell-Based Therapies  

NSDL National Science Digital Library

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

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

2001-07-01

324

The Effect of Centrifugation Condition on Mature Adipocytes and Adipose Stem Cell Viability.  

PubMed

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

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

2013-04-30

325

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

PubMed Central

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.

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

2013-01-01

326

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

Microsoft Academic Search

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.

Silvia K. Nicolis

2007-01-01

327

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

SciTech Connect

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

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

1995-03-30

328

STEM CELL NICHE: Structure and Function  

Microsoft Academic Search

Adult tissue-specific stem cells have the capacity to self-renew and generate functional differentiated cells that replenish lost cells throughout an organism's lifetime. Studies on stem cells from di- verse systems have shown that stem cell function is controlled by extracellular cues from the niche and by intrinsic genetic programs within the stem cell. Here, we review the remarkable progress re-

Linheng Li; Ting Xie

2005-01-01

329

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

PubMed

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

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

2012-12-17

330

Stem Cell Science in Iran  

Microsoft Academic Search

ABSTRACT Human embryonic,stem (hES) cells may potentially revolutionize biomedicine,through their use as a renewable source of cells for regenerative medicine. However, despite much promise the use and derivation of these cells in many countries is ethically challenging. Interestingly, stem cell research in Iran?s R oyan Institute is thriving despite m any challenges and has led to the generation of novel

David W. G. Morrison; Ali Khademhosseini

331

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

PubMed

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

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

2013-07-01

332

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

PubMed Central

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

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

2013-01-01

333

Immunomodulatory effects of human amniotic membrane-derived mesenchymal stem cells  

PubMed Central

Human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs) are capable of differentiating into several lineages and possess immunomodulatory properties. In this study, we investigated the soluble factor-mediated immunomodulatory effects of hAM-MSCs. Mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation was suppressed by hAM-MSCs in a dose-dependent manner as well as hAM-MSC culture supernatant. Moreover, interferon-gamma and interleukin (IL)-17 production significantly decreased from PBMC, whereas IL-10 from PBMCs and transforming growth factor beta (TGF-?) production from hAM-MSCs significantly increased in co-cultures of hAM-MSCs and PBMCs. Production of several MSC factors, including hepatocyte growth factor (HGF), TGF-?, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in hAM-MSCs co-cultured with PBMCs. These results indicate that the immunomodulatory effects of hAM-MSCs may be associated with soluble factors (TGF-?, HGF, PGE2, and IDO), suggesting that hAM-MSCs may have potential clinical use in regenerative medicine.

Kang, Jung Won; Hwang, Sun Young; Kang, Sung Keun; Ra, Jeong Chan; Lee, Moon Han

2012-01-01

334

The effects of vibration loading on adipose stem cell number, viability and differentiation towards bone-forming cells  

PubMed Central

Mechanical stimulation is an essential factor affecting the metabolism of bone cells and their precursors. We hypothesized that vibration loading would stimulate differentiation of human adipose stem cells (hASCs) towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue. We developed a vibration-loading device that produces 3g peak acceleration at frequencies of 50 and 100 Hz to cells cultured on well plates. hASCs were cultured using either basal medium (BM), osteogenic medium (OM) or adipogenic medium (AM), and subjected to vibration loading for 3 h d–1 for 1, 7 and 14 day. Osteogenesis, i.e. differentiation of hASCs towards bone-forming cells, was analysed using markers such as alkaline phosphatase (ALP) activity, collagen production and mineralization. Both 50 and 100 Hz vibration frequencies induced significantly increased ALP activity and collagen production of hASCs compared with the static control at 14 day in OM. A similar trend was detected for mineralization, but the increase was not statistically significant. Furthermore, vibration loading inhibited adipocyte differentiation of hASCs. Vibration did not affect cell number or viability. These findings suggest that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells.

Tirkkonen, Laura; Halonen, Heidi; Hyttinen, Jari; Kuokkanen, Hannu; Sievanen, Harri; Koivisto, Anna-Maija; Mannerstrom, Bettina; Sandor, George K. B.; Suuronen, Riitta; Miettinen, Susanna; Haimi, Suvi

2011-01-01

335

Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model.  

PubMed

Here we report an in vitro model system for studying the molecular and cellular mechanisms that underlie the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Embryonic stem cells (ESCs) derived from mice carrying normal or mutant transgenic alleles of the human SOD1 gene were used to generate motor neurons by in vitro differentiation. These motor neurons could be maintained in long-term coculture either with additional cells that arose during differentiation or with primary glial cells. Motor neurons carrying either the nonpathological human SOD1 transgene or the mutant SOD1(G93A) allele showed neurodegenerative properties when cocultured with SOD1(G93A) glial cells. Thus, our studies demonstrate that glial cells carrying a human SOD1(G93A) mutation have a direct, non-cell autonomous effect on motor neuron survival. More generally, our results show that ESC-based models of disease provide a powerful tool for studying the mechanisms of neural degeneration. These phenotypes displayed in culture could provide cell-based assays for the identification of new ALS drugs. PMID:17435754

Di Giorgio, Francesco Paolo; Carrasco, Monica A; Siao, Michelle C; Maniatis, Tom; Eggan, Kevin

2007-04-15

336

The effects of vibration loading on adipose stem cell number, viability and differentiation towards bone-forming cells.  

PubMed

Mechanical stimulation is an essential factor affecting the metabolism of bone cells and their precursors. We hypothesized that vibration loading would stimulate differentiation of human adipose stem cells (hASCs) towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue. We developed a vibration-loading device that produces 3g peak acceleration at frequencies of 50 and 100 Hz to cells cultured on well plates. hASCs were cultured using either basal medium (BM), osteogenic medium (OM) or adipogenic medium (AM), and subjected to vibration loading for 3 h d(-1) for 1, 7 and 14 day. Osteogenesis, i.e. differentiation of hASCs towards bone-forming cells, was analysed using markers such as alkaline phosphatase (ALP) activity, collagen production and mineralization. Both 50 and 100 Hz vibration frequencies induced significantly increased ALP activity and collagen production of hASCs compared with the static control at 14 day in OM. A similar trend was detected for mineralization, but the increase was not statistically significant. Furthermore, vibration loading inhibited adipocyte differentiation of hASCs. Vibration did not affect cell number or viability. These findings suggest that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells. PMID:21613288

Tirkkonen, Laura; Halonen, Heidi; Hyttinen, Jari; Kuokkanen, Hannu; Sievänen, Harri; Koivisto, Anna-Maija; Mannerström, Bettina; Sándor, George K B; Suuronen, Riitta; Miettinen, Susanna; Haimi, Suvi

2011-05-25

337

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

Microsoft Academic Search

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

Joy Yueyue Zhang

2011-01-01

338

Effect of allogeneic stem cell transplantation on bone marrow angiogenesis in chronic myelogenous leukemia  

Microsoft Academic Search

Increased bone marrow angiogenesis is a poor prognostic marker in patients with chronic myelogenous leukemia (CML). Allogeneic stem cell transplantation (ASCT) can be curative for patients with CML. Studies in myeloma have shown persistent increased bone marrow microvessel density (MVD) after autologous transplantation. It is not clear if abnormal bone marrow angiogenesis persists following a curative intervention like allogeneic transplantation.

S Kumar; M R Litzow; S V Rajkumar

2003-01-01

339

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

ERIC Educational Resources Information Center

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

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

2011-01-01

340

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

Microsoft Academic Search

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

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

2004-01-01

341

Neural stem cell therapy for neurological diseases: dreams and reality  

Microsoft Academic Search

There is a pressing need for treatments for neurodegenerative diseases. Hopes have been raised by the prospect of neural stem cell therapy; however, despite intense research activities and media attention, stem cell therapy for neurological disorders is still a distant goal. Effective strategies must be developed to isolate, enrich and propagate homogeneous populations of neural stem cells, and to identify

Ferdinando Rossi; Elena Cattaneo

2002-01-01

342

Endometrial Stem Cells and Reproduction  

PubMed Central

Abnormal endometrial function remains a significant cause of implantation failure, recurrent pregnancy loss, and other pathologies responsible for female infertility. The development of novel therapies to treat infertility due to endometrial dysfunction requires an understanding of the latest advancements in endometrial cell biology, such as the role of endometrial stem cells. The remarkable regenerative capacity of the human endometrium is absolutely essential for successful reproduction and likely requires a population of stem cells in the endometrium. The purpose of this review is to provide an introduction to some of the newest concepts in endometrial stem cell biology.

Morelli, Sara S.; Yi, Pauline; Goldsmith, Laura T.

2012-01-01

343

Immunological characteristics of mesenchymal stem cells.  

PubMed

Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine. PMID:23580887

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

2013-01-01

344

Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro  

PubMed Central

Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s) between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to have multiple roles in follicle development. Granulosa and theca cells were isolated from 2–6 mm healthy follicles of mature porcine ovaries and cultured under serum-free conditions, supplemented with: 100 ng/ml LR3 IGF-1, 10 ng/ml insulin, 100 ng/ml testosterone, 0–10 ng/ml SCF, 1 ng/ml FSH (granulosa), 0.01 ng/ml LH (theca) or 1 ng/ml FSH and 0.01 ng/ml LH (co-culture) and with/without oocyte conditioned medium (OCM) or 5 oocytes. Cells were cultured in 96 well plates for 144 h, after which viable cell numbers were determined. Medium was replaced every 48 h and spent medium analysed for steroids. Oocyte secreted factors were shown to stimulate both granulosa cell proliferation (P < 0.001) and oestradiol production (P < 0.001) by granulosa cells throughout culture. In contrast, oocyte secreted factors suppressed granulosa cell progesterone production after both 48 and 144 hours (P < 0.001). Thecal cell numbers were increased by oocyte secreted factors (P = 0.02), together with a suppression in progesterone and androstenedione synthesis after 48 hours (P < 0.001) and after 144 hours (P = 0.02), respectively. Oocyte secreted factors also increased viable cell numbers (P < 0.001) in co-cultures together with suppression of progesterone (P < 0.001) and oestradiol (P < 0.001). In granulosa cell only cultures, SCF increased progesterone production in a dose dependent manner (P < 0.001), whereas progesterone synthesis by theca cells was reduced in a dose dependent manner (P = 0.002). Co-cultured cells demonstrated an increase in progesterone production with increasing SCF dose (P < 0.001) and an increase in oestradiol synthesis at the highest dose of SCF (100 ng/ml). In summary, these findings demonstrate the presence of a co-ordinated paracrine interaction between somatic cells and germ cells, whereby oocyte derived signals interact locally to mediate granulosa and theca cell function. SCF has a role in modulating this local interaction. In conclusion, the oocyte is an effective modulator of granulosa-theca interactions, one role being the inhibition of luteinization.

Brankin, Victoria; Mitchell, Marcus RP; Webb, Bob; Hunter, Morag G

2003-01-01

345

Sex Steroids and Stem Cell Function  

PubMed Central

Gender dimorphisms exist in the pathogenesis of a variety of cardiovascular, cardiopulmonary, neurodegenerative, and endocrine disorders. Estrogens exert immense influence on myocardial remodeling following ischemic insult, partially through paracrine growth hormone production by bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells. Estrogens also facilitate the mobilization of endothelial progenitor cells to the ischemic myocardium and enhance neovascularization at the ischemic border zone. Moreover, estrogens limit pathological myocardial remodeling through the inhibitory effects on the proliferation of the cardiac fibroblasts. Androgens also may stimulate endothelial progenitor cell migration from the bone marrow, yet the larger role of androgens in disease pathogenesis is not well characterized. The beneficial effects of sex steroids include alteration of lipid metabolism in preadipocytes, modulation of bone metabolism and skeletal maturation, and prevention of osteoporosis through their effects on osteogenic precursors. In an example of sex steroid-specific effects, neural stem cells exhibit enhanced proliferation in response to estrogens, whereas androgens mediate inhibitory effects on their proliferation. Although stem cells can offer significant therapeutic benefits in various cardiovascular, neurodegenerative, endocrine disorders, and disorders of bone metabolism, a greater understanding of sex hormones on diverse stem cell populations is required to improve their ultimate clinical efficacy. In this review, we focus on the effects of estrogen and testosterone on various stem and progenitor cell types, and their relevant intracellular mechanisms.

Ray, Rinki; Novotny, Nathan M; Crisostomo, Paul R; Lahm, Tim; Abarbanell, Aaron; Meldrum, Daniel R

2008-01-01

346

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

SciTech Connect

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.

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

347

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

PubMed Central

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

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

2013-01-01

348

The effect of cannabichromene on adult neural stem/progenitor cells.  

PubMed

Apart from the psychotropic compound ?(9)-tetrahydrocannabinol (THC), evidence suggests that other non-psychotropic phytocannabinoids are also of potential clinical use. This study aimed at elucidating the effect of major non-THC phytocannabinoids on the fate of adult neural stem progenitor cells (NSPCs), which are an essential component of brain function in health as well as in pathology. We tested three compounds: cannabidiol, cannabigerol, and cannabichromene (CBC), and found that CBC has a positive effect on the viability of mouse NSPCs during differentiation in vitro. The expression of NSPC and astrocyte markers nestin and Glial fibrillary acidic protein (GFAP), respectively, was up- and down-regulated, respectively. CBC stimulated ERK1/2 phosphorylation; however, this effect had a slower onset in comparison to typical MAPK stimulation. A MEK inhibitor, U0126, antagonized the up-regulation of nestin but not the down-regulation of GFAP. Based on a previous report, we studied the potential involvement of the adenosine A1 receptor in the effect of CBC on these cells and found that the selective adenosine A1 receptor antagonist, DPCPX, counteracted both ERK1/2 phosphorylation and up-regulation of nestin by CBC, indicating that also adenosine is involved in these effects of CBC, but possibly not in CBC inhibitory effect on GFAP expression. Next, we measured ATP levels as an equilibrium marker of adenosine and found higher ATP levels during differentiation of NSPCs in the presence of CBC. Taken together, our results suggest that CBC raises the viability of NSPCs while inhibiting their differentiation into astroglia, possibly through up-regulation of ATP and adenosine signalling. PMID:23941747

Shinjyo, Noriko; Di Marzo, Vincenzo

2013-08-11

349

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

PubMed

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

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

2012-04-22

350

N-3 PUFAs have antiproliferative and apoptotic effects on human colorectal cancer stem-like cells in vitro.  

PubMed

The n-3 polyunsaturated fatty acids have been shown to inhibit the induction and progression of many kinds of tumor and to increase the therapeutic effects of numerous chemotherapeutics, but their anticancer effect on cancer stem cells from colorectal cancer has not been described previously. In the present study, we cultivated spheres from the SW620 cell line in serum-free medium and evaluated the features of the spheres by immunofluorescence, cell cycle distribution, resistance to chemotherapeutics and soft agar clone formation, and the spheres were shown to be cancer stem-like cells through tumorigenicity in athymic nude mice. Reverse transcriptase polymerase chain reaction analysis of pluripotency genes, such as Sox-2, Oct-4 and Bmi-1, showed that the spheres were generated by dedifferentiation of SW620 cells. The study explored the use of n-3 polyunsaturated fatty acids (PUFAs) in spheres, which were treated with two n-3 PUFAs [docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA)]. Treatment of the spheres with DHA and EPA alone or in combination for 72 h led to apoptosis and the progressive loss of viability and DNA fragmentation and an increase in annexin V expression. DHA and EPA can enhance the chemotherapeutic sensitivity effect of 5-Fu and mitomycin C, especially DHA combined with EPA. Taken together, these results provide evidence that n-3 PUFAs exert a direct anticancer action that may contribute to their antiproliferative and proapoptotic effect on the cancer stem-like cells. PMID:22854319

Yang, Ting; Fang, Shi; Zhang, Hai-Xia; Xu, Li-Xiao; Zhang, Zhan-Qiang; Yuan, Kai-Tao; Xue, Cong-Long; Yu, Hong-Lan; Zhang, Sheng; Li, Yu-Fei; Shi, Han-Ping; Zhang, Yan

2012-07-31

351

Effect of collagen II coating on mesenchymal stem cell adhesion on chitosan and on reacetylated chitosan fibrous scaffolds  

Microsoft Academic Search

The biocompatibility and biomimetic properties of chitosan make it attractive for tissue engineering but its use is limited\\u000a by its cell adhesion properties. Our objectives were to produce and characterize chitosan and reacetylated-chitosan fibrous\\u000a scaffolds coated with type II collagen and to evaluate the effect of these chemical modifications on mesenchymal stem cell\\u000a (MSC) adhesion. Chitosan and reacetylated-chitosan scaffolds obtained

Guillaume R. RagetlyDominique; Dominique J. Griffon; Hae-Beom Lee; Yong Sik Chung

2010-01-01

352

Effects of a bone-like mineral film on phenotype of adult human mesenchymal stem cells in vitro  

Microsoft Academic Search

Multipotent cell types are rapidly becoming key components in a variety of tissue engineering schemes,and mesenchymal stem cells (MSCs) are emerging as an important tool in bone tissue regeneration. Although several soluble signals influencing osteogenic differentiation of MSCs in vitro are well-characterized,relatively little is known about the influence of substrate signals. This study was aimed at elucidating the effects of

William L. Murphya; Susan Hsiong; Thomas P. Richardson; Craig A. Simmons; David J. Mooneya

2004-01-01

353

Stem cell therapy for the spinal cord  

PubMed Central

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

2012-01-01

354

Global irradiation effects, stem cell genes and rare transcripts in the planarian transcriptome.  

PubMed

Stem cells are the closest relatives of the totipotent primordial cell, which is able to spawn millions of daughter cells and hundreds of cell types in multicellular organisms. Stem cells are involved in tissue homeostasis and regeneration, and may play a major role in cancer development. Among animals, planarians host a model stem cell type, called the neoblast, which essentially confers immortality. Gaining insights into the global transcriptional landscape of these exceptional cells takes an unprecedented turn with the advent of Next Generation Sequencing methods. Two Digital Gene Expression transcriptomes of Schmidtea mediterranea planarians, with or without neoblasts lost through irradiation, were produced and analyzed. Twenty one bp NlaIII tags were mapped to transcripts in the Schmidtea and Dugesia taxids. Differential representation of tags in normal versus irradiated animals reflects differential gene expression. Canonical and non-canonical tags were included in the analysis, and comparative studies with human orthologs were conducted. Transcripts fell into 3 categories: invariant (including housekeeping genes), absent in irradiated animals (potential neoblast-specific genes, IRDOWN) and induced in irradiated animals (potential cellular stress response, IRUP). Different mRNA variants and gene family members were recovered. In the IR-DOWN class, almost all of the neoblast-specific genes previously described were found. In irradiated animals, a larger number of genes were induced rather than lost. A significant fraction of IRUP genes behaved as if transcript versions of different lengths were produced. Several novel potential neoblast-specific genes have been identified that varied in relative abundance, including highly conserved as well as novel proteins without predicted orthologs. Evidence for a large body of antisense transcripts, for example regulated antisense for the Smed-piwil1 gene, and evidence for RNA shortening in irradiated animals is presented. Novel neoblast-specific candidates include a peroxiredoxin protein that appears to be preferentially expressed in human embryonic stem cells. PMID:22450998

Galloni, Mireille

2012-01-01

355

Idiotype protein-pulsed dendritic cells produce strong anti-myeloma effects after syngeneic stem cell transplantation in mice.  

PubMed

Dendritic cell (DC) vaccination represents an interesting immunotherapeutic option in the treatment of several malignancies. In multiple myeloma (MM) patients, vaccination with autologous idiotype (Id) protein-pulsed DC is feasible, but their antitumoral effectiveness was rather limited. To improve the therapeutic potential of DC therapy, we studied the immunological effects of syngeneic peripheral blood stem cell transplantation (PBSCT) given in conjunction with Id-loaded DC. Balb/c mice were inoculated i.p. with 5 x 10(5) of HOPC myeloma cells (Balb/c origin). Animals were immunized with three injections of 5 x 10(5) DC pulsed with the IgG2a(HOPC) or with a control immunoglobulin (Ig(control)). Some experimental groups of myeloma-bearing animals received total body irradiation (7.5 Gy) and a subsequent transplant of 2 x 10(7)syngeneic peripheral blood progenitor cells (PBPC) followed by DC therapy beginning at day 10 post transplant. Animals receiving DC therapy or syngeneic PBPCT alone neither induce long-term survival nor tumor-specific CTL reactivity in vitro. In marked contrast, combination of syngeneic PBPC transplantation and subsequent DC therapy resulted in 78% survival after a follow-up of 180 days. In addition, this treatment modality conferred a generation of Id peptide-specific CD8-mediated T cell reactivity. These data provide a rationale for DC-based vaccination in multiple myeloma patients administered post syngeneic transplantation. PMID:11859393

Zeis, M; Frenzke, H; Schmitz, N; Uharek, L; Steinmann, J

2002-02-01

356

Effects of mechanical and chemical stimuli on ?differentiation of human adipose-derived stem ?cells into endothelial cells.  

PubMed

It has been hypothesized that application of the micromechanical environment that target cells experience in vivo enhances functionality of differentiated cells. Vascular endothelial cells, functioning at the interface of the blood-vessel wall, are vital to the performance of the cardiovascular system. They are subject to shear and tensile stresses induced by blood flow and pressure, respectively.?This study investigated effects of shear/tensile stresses on endothelial differentiation of adipose-?derived mesenchymal stem cells (ASCs) utilizing a custom-made bioreactor capable of applying both shear and tensile stresses. The loading values of 10% cyclic stretch, 0-2.5 dyn/cm2 cyclic shear stress, and combined loadings were used. To examine the extent of mechanical and chemical stimuli in ?acquisition of endothelial characteristics by ASCs, the expression of three major endothelial genes were quantified when ASCs were treated by three loading regimes and endothelial growth factor for three different durations (1, 2, and 7 days). In general, cyclic stretch decreased expression of FLK-1 ?and vWF, while cyclic shear elevated expression levels. The combined loading regime had minor ?effects on the expression of the two markers. All types of loadings significantly enhanced the expression level of VE-cadherin with the most prominent increase by combined loading. It was concluded that applying different loading regimes assists in adjusting the expression level of endothelial markers to achieve functional endothelial cells for cardiovascular engineering. PMID:23918273

Shojaei, Shahrokh; Tafazzoli-Shahdpour, Mohamad; Shokrgozar, Mohamad Ali; Haghighipour, Nooshin

2013-08-02

357

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

PubMed

Plasma cell leukemia (PCL) is a rare disease that represents approximately 4% of plasma cell malignant disorders. PCL consists of two variants: primary PCL presents in patients with no previous history of multiple myeloma, while secondary PCL consists of a leukemic transformation in a previously recognized multiple myeloma. Primary PCL is an extremely resistant, rapidly progressive, fatal disease, with a median overall survival of 6.8 months. There is no standard therapeutic strategy, because no treatment option has been prospectively evaluated. We describe a successful case of newly diagnosed primary PCL, treated with a regimen that included bortezomib, followed by auto stem cell transplantation and nonmyeloablative allogeneic stem cell transplantation. Our patient has maintained remission status for over 12 months since undergoing the allogeneic stem cell transplantation. This strategy is promising for PCL, which, though an extremely resistant disease, may become curable. PMID:23754921

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

2012-07-06

358

Microbioreactors for Stem Cell Research  

NASA Astrophysics Data System (ADS)

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

Freytes, Donald O.; Vunjak-Novakovic, Gordana

359

Effect of stem cell factor on myelopoiesis potential in human Dexter-type culture systems.  

PubMed

Hematopoiesis is influenced by the presence of the hematopoietic microenvironment, and Dexter-type liquid culture systems represent an in vitro representation of some aspects of the microenvironment that are optimal for the propagation of myeloid progenitors. Marrow stromal layers, which constitute part of these culture systems, produce growth factors, including stem cell factor (SCF), a ligand for the c-kit proto-oncogene that has been found to increase detection of myeloid, erythroid, and megakaryocytic progenitors in short-term marrow colony assays. In this work, the role of SCF in Dexter-type culture systems was examined to better define its contribution to steady-state myelopoiesis. When cultured in the continued presence of 100 ng/mL SCF, both primary and recharged cultures demonstrated significantly greater CFU-GM output, with quantitative differences noted throughout culture duration (up to 6 weeks). This increase in CFU-GM could be inhibited specifically with the addition of 1:1500 SR-1, a neutralizing anti-c-kit monoclonal antibody (MAb) that neutralizes the biological effects of SCF, and the increase was noted both with recharged light-density marrow cells and purified CD34+ progenitor cells. On the other hand, when primary or recharged marrow cultures were established in the absence of exogenous SCF, but in the continuous presence of SR-1, no inhibition of CFU-GM output was observed. When light-density marrow cells were purged of pre-existing CFU-GM by 4-hydroperoxycyclophosphamide (4-HC) and were seeded over irradiated stromal layers, exogenous SCF resulted in detection of CFU-GM from 4-HC-treated cells as early as 1 week of culture, as compared to the lack of significant emergence of CFU-GMs at 4 weeks in the control cultures. This SCF effect was also inhibited by SR-1. Purified CD34+ progenitor cells did not adhere to SCF immobilized to tissue culture plates, and the adhesion of such progenitors to murine Steel lines transfected with membrane-bound SCF was not greater than to the parent nontransfected Steel line, suggesting that the effect of SCF was not on CD34+ cell adhesion. These studies confirm the action of SCF at a pre-CFU level, and they demonstrate the ability of SCF to stimulate increased production of myeloid progenitors in long-term liquid culture systems. PMID:7533098

Liesveld, J L; Broudy, V C; Harbol, A W; Abboud, C N

1995-03-01

360

Tolerogenic effect of non-inherited maternal antigens in hematopoietic stem cell transplantation  

PubMed Central

Major histocompatibility complex antigens that provoke severe transplant reactions are referred to as the human leukocyte antigen (HLA) in human and as the H-2 in mice. Even if the donor and recipient are HLA-identical siblings, graft-versus-host reactions have been linked to differences in the minor histocompatibility antigen. As the chance of finding an HLA-identical sibling donor is only 25%, attention has been focused on using alternative donors. An HLA-mismatched donor with non-inherited maternal antigens (NIMA) is less immunogenic than that with non-inherited paternal antigens, because the contact between the immune systems of the mother and child during pregnancy affects the immune response of the child against NIMA. However, the immunologic effects of developmental exposure to NIMA are heterogeneous, and can be either tolerogenic or immunogenic. We recently have devised a novel method for predicting the tolerogenic effect of NIMA. In this review, we overview the evidence for the existence of the NIMA tolerogenic effect, the possible cellular and molecular basis of the phenomenon, and its utilization in hematopoietic stem cell transplantation. We suggest a future direction for the safe clinical use of this phenomenon, fetomaternal tolerance, in the transplantation field.

Hirayama, Masahiro; Azuma, Eiichi; Komada, Yoshihiro

2012-01-01

361

28. Embryonic and adult stem cell therapy  

Microsoft Academic Search

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

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

2003-01-01

362

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

PubMed

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

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

2012-07-04

363

Effect of Cardiac Stem Cells in Patients with Ischemic Cardiomyopathy: Initial Results of the SCIPIO Trial  

PubMed Central

Summary Background C-kit+ lineage? cardiac stem cells (CSCs) improve postinfarction left ventricular (LV) dysfunction in animals; however, their efficacy in humans is unknown. Methods In February 2009, we began SCIPIO (Stem Cell Infusion in Patients with Ischemic CardiOmyopathy), a Phase I, randomized, open-label trial of CSCs in patients with postinfarction LV dysfunction (ejection fraction [EF] ? 40%) who underwent coronary bypass surgery. Autologous CSCs were isolated from the right atrial appendage and re-infused intracoronarily 4 ± 1 months after surgery; controls received no treatment. In Stage A, 9 treated and 4 control patients were consecutively enrolled to assess the feasibility and short-term safety of CSCs. Then, in Stage B, patients were randomized to the treated or control arm in a 2:3 ratio using a block randomization scheme and a block size of five. Primary (safety) and secondary (efficacy) endpoints were assessed at serial times after enrollment. Findings Autologous CSCs were successfully isolated and expanded in 80 out of 81 patients. In 16 treated patients, no CSC-related adverse effects have been observed. LVEF (3D echocardiography) increased from 30.3 ± 1.9% before CSC infusion to 38.5 ± 2.8% at 4 months after infusion, (P=0.001, n=14). This was associated with an improvement in regional wall motion score index (echocardiography) (1.91 ± 0.09 vs. 1.73 ± 0.09, P=0.005), NYHA functional class (2.19 ± 0.16 vs. 1.63 ± 0.16, P=0.003), and quality of life (MLHFQ score, 46.44 ± 5.22 vs. 26.69 ± 4.92, P<0.0001). In contrast, in 7 control patients, none of these variables changed appreciably during the corresponding time-interval. Importantly, the salubrious effects of CSCs were even more pronounced at 1 year (e.g., LVEF increased by 12.3 ± 2.1% vs. pre-CSCs, P=0.0007, n=8), suggesting that CSCs continue to improve LV function beyond the first 4 months. In the 7 treated patients in whom cardiac magnetic resonance (cMR) imaging could be performed, infarct size decreased by 7.8 ± 1.7 g (23.8%) at 4 months (P=0.004) and 9.8 ± 3.5 g (30.3%) at 1 year (P=0.04). Interpretation These initial results in humans are very encouraging, and suggest that infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure.

Bolli, Roberto; Chugh, Atul R.; D'Amario, Domenico; Loughran, John H.; Stoddard, Marcus F.; Ikram, Sohail; Beache, Garth M.; Wagner, Stephen G.; Leri, Annarosa; Hosoda, Toru; Elmore, Julius B.; Goihberg, Polina; Cappetta, Donato; Solankhi, Naresh K.; Fahsah, Ibrahim; Rokosh, D. Gregg; Slaughter, Mark S.; Kajstura, Jan; Anversa, Piero

2011-01-01

364

Effect of titanium surface topographies on human bone marrow stem cells differentiation in vitro.  

PubMed

Coating characteristics of dental implants such as composition and topography regulate cell response during implant healing. The aim of this study was to assess how surface topography can affect osteogenic differentiation of mesenchymal stem cells (MSCs) by analyzing the expression levels of bone-related genes and MSCs marker. Thirty disk-shaped, commercially pure Grade 2 titanium samples (10 × 2 mm) with 3 different surface topographies (DENTSPLY-Friadent GmbH, Mannheim, Germany) were used in the present study: 10 Ti machined disks (control), 10 Ti sandblasted and acid-etched disks (DPS(®)) and 10 sandblasted and acid-etched disks at high temperature (Plus(®)). Samples were processed for real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. By comparing machined and Plus(®) disks, quantitative real-time RT-PCR showed a significant reduction of the bone-related genes osteocalcin (BGLAP) and osteoblast transcriptional factor (RUNX2). The comparison between DPS(®) and Plus(®) disks showed a slight induction of all the genes examined (RUNX2, ALPL, COL1A1, COL3A1, ENG, FOSL1, SPP1, and SP7); only the expression of BGLAP remained stable. The present study, demonstrated that implant surface topography affects osteoblast gene expression. Indeed, Plus(®) surface produces an effect on MSCs in the late differentiation stages. PMID:22678711

Perrotti, Vittoria; Palmieri, Annalisa; Pellati, Agnese; Degidi, Marco; Ricci, Laura; Piattelli, Adriano; Carinci, Francesco

2012-06-08

365

Effects of Substrate Mechanics on Contractility of Cardiomyocytes Generated from Human Pluripotent Stem Cells  

PubMed Central

Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4–99.7?kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for ?-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies.

Hazeltine, Laurie B.; Simmons, Chelsey S.; Salick, Max R.; Lian, Xiaojun; Badur, Mehmet G.; Han, Wenqing; Delgado, Stephanie M.; Wakatsuki, Tetsuro; Crone, Wendy C.; Pruitt, Beth L.; Palecek, Sean P.

2012-01-01

366

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

NASA Astrophysics Data System (ADS)

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.

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

367

Stem Cells in the Lung  

PubMed Central

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

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

2007-01-01

368

Brain Tumor Stem Cell Markers  

Microsoft Academic Search

Brain tumors display striking heterogeneity of cellular morphology and differentiation status. Recent studies have identified\\u000a tumor subpopulations in several brain tumor types that self-renew and can propagate tumor formation in mice models. These\\u000a cells, called tumor stem cells, are defined functionally but several markers are under investigation to identify brain tumor\\u000a stem cells. Although no marker has proven absolutely informative

Jeremy N. Rich

369

Neurorestorative effect of urinary bladder matrix-mediated neural stem cell transplantation following traumatic brain injury in rats.  

PubMed

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 (0.5x10(5) cells/µl) cultured in a bioactive scaffold derived from porcine urinary bladder matrix (UBM; 4 injection sites, 2.5µl 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

Wang, J Y; Liou, A K F; Ren, Z H; Zhang, L; Brown, B N; Cui, X T; Badylak, S F; Cai, Y N; Guan, Y Q; Leak, Rehana K; Chen, J; Ji, X; Chen, L

2013-05-01

370

Stem cell platforms for regenerative medicine.  

PubMed

The pandemic of chronic degenerative diseases associated with aging demographics mandates development of effective approaches for tissue repair. As diverse stem cells directly contribute to innate healing, the capacity for de novo tissue reconstruction harbors a promising role for regenerative medicine. Indeed, a spectrum of natural stem cell sources ranging from embryonic to adult progenitors has been recently identified with unique characteristics for regeneration. The accessibility and applicability of the regenerative armamentarium has been further expanded with stem cells engineered by nuclear reprogramming. Through strategies of replacement to implant functional tissues, regeneration to transplant progenitor cells or rejuvenation to activate endogenous self-repair mechanisms, the overarching goal of regenerative medicine is to translate stem cell platforms into practice and achieve cures for diseases limited to palliative interventions. Harnessing the full potential of each platform will optimize matching stem cell-based biologics with the disease-specific niche environment of individual patients to maximize the quality of long-term management, while minimizing the needs for adjunctive therapy. Emerging discovery science with feedback from clinical translation is therefore poised to transform medicine offering safe and effective stem cell biotherapeutics to enable personalized solutions for incurable diseases. PMID:19779576

Nelson, Timothy J; Behfar, Atta; Yamada, Satsuki; Martinez-Fernandez, Almudena; Terzic, Andre

2009-06-01

371

Stem Cell Platforms for Regenerative Medicine  

PubMed Central

The pandemic of chronic degenerative diseases associated with aging demographics mandates development of effective approaches for tissue repair. As diverse stem cells directly contribute to innate healing, the capacity for de novo tissue reconstruction harbors a promising role for regenerative medicine. Indeed, a spectrum of natural stem cell sources ranging from embryonic to adult progenitors has been recently identified with unique characteristics for regeneration. The accessibility and applicability of the regenerative armamentarium has been further expanded with stem cells engineered by nuclear reprogramming. Through strategies of replacement to implant functional tissues, regeneration to transplant progenitor cells or rejuvenation to activate endogenous self-repair mechanisms, the overarching goal of regenerative medicine is to translate stem cell platforms into practice and achieve cures for diseases limited to palliative interventions. Harnessing the full potential of each platform will optimize matching stem cell-based biologics with the disease-specific niche environment of individual patients to maximize the quality of long-term management, while minimizing the needs for adjunctive therapy. Emerging discovery science with feedback from clinical translation is therefore poised to transform medicine offering safe and effective stem cell biotherapeutics to enable personalized solutions for incurable diseases.

Nelson, Timothy J.; Behfar, Atta; Yamada, Satsuki; Martinez-Fernandez, Almudena; Terzic, Andre

2009-01-01

372

Planarian Regeneration and Stem Cells  

NSDL National Science Digital Library

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

Alejandro SĂ¡nchez Alvarado (Howard Hughes Medical Institute;)

2007-03-31

373

Stem cells, dot-com.  

PubMed

Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned because of the Internet. Despite very limited approval for use, DTC stem cell-marketed "treatments" have emerged for an array of conditions, creating global public health and safety risks. However, it remains unclear whether such use of stem cells is subject to drugs or biologics regulations. To address this gap, regulatory agencies should be given clear authority, and the international community should create a framework for appropriate stem cell use. In addition, consumer protection laws should be used to scrutinize providers. PMID:22972840

Liang, Bryan A; Mackey, Tim K

2012-09-12

374

Progress in myeloma stem cells  

PubMed Central

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.

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

2011-01-01

375

Phenotype-independent effects of retroviral transduction in human dental pulp stem cells.  

PubMed

An immortalized human dental pulp stem cell (DPSC) line of an odontoblastic phenotype is established to circumvent the normal programmed senescence and to maintain the cell line's usefulness as a tool for further study of cellular activity. DPSCs are isolated from human dental pulp tissues and transfected using hTERT. The influence of this process on the DPSC phenotype and the mRNA expression of oncogenes involved in cellular senescence is investigated. The results reveal an absence of altered DPSC morphology and phenotype following the exogenous introduction of the hTERT gene, which is coupled with a significant reduction in p16 mRNA expression. This provides insight into how to circumvent in vitro dental pulp stem cell death following the exogenous introduction of hTERT. PMID:23765615

Egbuniwe, Obi; Grant, Andrew D; Renton, Tara; Di Silvio, Lucy

2013-06-14

376

The effect of lipoaspirates cryopreservation on adipose-derived stem cells.  

PubMed

Background: Autologous fat grafting has gained popularity, particularly with the discovery of adipose-derived stem cells (ADSC). The possibility of freezing lipoaspirates (LA) for later use has intriguing clinical potential. However, the effect of LA cryopreservation on ADSC is unclear. Objectives: The authors explore the effect of LA cryopreservation on ADSC viability. Methods: Human LA (n = 8) were harvested using a standard technique. Lipoaspirate samples were either processed immediately as fresh LA (A) or stored at -20°C and then at -80°C for 30 days with (B) or without (C) freezing medium. Stromal vascular fraction (SVF) was separated from adipocytes and either cultured to obtain purified ADSC or processed for the isolation of 3 distinct ADSC subpopulations (CD90(+)/CD45(-), CD105(+)/CD45(-), and CD34(+)/CD31(-)). Apoptosis and necrosis were determined by an annexin V/propidium iodide assay and quantified by flow cytometry. The capability of ADSC for long-term proliferation and differentiation was also examined. Results: There were no significant differences in the apoptosis and necrosis of adipocytes, SVF, or ADSC between groups A and B. However, cell viability in SVF and ADSC was significantly compromised in group C as compared with group B (P < .01) due to higher ADSC apoptosis but not necrosis. The viable ADSC isolated from fresh or frozen LA were cultured for more than 20 passages and demonstrated similar patterns and speed of proliferation with strong capability to differentiate, evidenced by cell doubling time and positive staining with Oil Red O (Sigma-Aldrich, St Louis, Missouri) and alkaline phosphatase. Conclusions: Lipoaspirates cryopreservation had a significant impact on ADSC apoptosis but not on ADSC necrosis, proliferation, or differentiations. Freezing medium provides significant protection against ADSC apoptosis. PMID:23966549

Wang, Wei Z; Fang, Xin-Hua; Williams, Shelley J; Stephenson, Linda L; Baynosa, Richard C; Wong, Nancy; Khiabani, Kayvan T; Zamboni, William A

2013-08-21

377

Glucocorticoids induce long-lasting effects in neural stem cells resulting in senescence-related alterations.  

PubMed

Alterations in intrauterine programming occurring during critical periods of development have adverse consequences for whole-organ systems or individual tissue functions in later life. In this paper, we show that rat embryonic neural stem cells (NSCs) exposed to the synthetic glucocorticoid dexamethasone (Dex) undergo heritable alterations, possibly through epigenetic mechanisms. Exposure to Dex results in decreased NSC proliferation, with no effects on survival or differentiation, and changes in the expression of genes associated with cellular senescence and mitochondrial functions. Dex upregulates cell cycle-related genes p16 and p21 in a glucocorticoid receptor(GR)-dependent manner. The senescence-associated markers high mobility group (Hmg) A1 and heterochromatin protein 1 (HP1) are also upregulated in Dex-exposed NSCs, whereas Bmi1 (polycomb ring finger oncogene) and mitochondrial genes Nd3 (NADH dehydrogenase 3) and Cytb (cytochrome b) are downregulated. The concomitant decrease in global DNA methylation and DNA methyltransferases (Dnmts) suggests the occurrence of epigenetic changes. All these features are retained in daughter NSCs (never directly exposed to Dex) and are associated with a higher susceptibility to oxidative stress, as shown by the increased occurrence of apoptotic cell death on exposure to the redox-cycling reactive oxygen species (ROS) generator 2,3-dimethoxy-1-naphthoquinone (DMNQ). Our study provides novel evidence for programming effects induced by glucocorticoids (GCs) on NSCs and supports the idea that fetal exposure to endogenous or exogenous GCs is likely to result in long-term consequences that may predispose to neurodevelopmental and/or neurodegenerative disorders. PMID:21368868

Bose, R; Moors, M; Tofighi, R; Cascante, A; Hermanson, O; Ceccatelli, S

2010-11-04

378

Hematopoietic Stem Cell Aging: Wrinkles In Stem Cell Potential  

Microsoft Academic Search

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

S. M. Chambers; M. A. Goodell

2007-01-01

379

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

Microsoft Academic Search

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

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

2010-01-01

380

Effects of human placental serum on proliferation and morphology of human adipose tissue-derived stem cells  

Microsoft Academic Search

Media used for tissue culture may have significant effects on the growth and morphology of the adipose tissue-derived stem cells (ADSCs). As fetal bovine serum (FBS) may induce an immunological reaction and health risks, this study was designed to evaluate and compare the effects of human placental serum (HPS) on the proliferation and morphology of hADSCs. We cultured hADSCs for

H Shafaei; A Esmaeili; M Mardani; S Razavi; B Hashemibeni; M H Nasr-Esfahani; M B Shiran; E Esfandiari

2011-01-01

381

Advances in stem cell therapy for spinal cord injury  

PubMed Central

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.

Mothe, Andrea J.; Tator, Charles H.

2012-01-01

382

Direct Effect of Chenodeoxycholic Acid on Differentiation of Mouse Embryonic Stem Cells Cultured under Feeder-Free Culture Conditions  

PubMed Central

Chenodeoxycholic acid (CDCA), a farnesoid X receptor (FXR) ligand, is a member of the nuclear receptor family and is probably involved in regulating the cellular activities of embryonic stem (ES) cells. Recently, although it was reported that the FXR ligand can mediate differentiation, apoptosis, and/or growth arrest in several cell types, it is still not well known how CDCA mediates effects in ES cells. Therefore, we investigated the direct effect of CDCA on mES cells. Feeder-free mES cells were treated in a dose-dependent manner with CDCA (50, 100, and 200??M) for 72?h, and then a 100??M CDCA treatment was performed for an additional 72?h. We analyzed the morphology, cell growth, cell characteristics, immunocytochemistry, and RT-PCR. In CDCA-treated cells, we observed the disappearance of pluripotent stem cell markers including alkaline phosphatase, Oct4, and Nanog and a time- and dose-dependent increase in expression of nestin, PAX6, and ?-smooth muscle actin, but not ?-fetoprotein. The 100??M CDCA-treated cells in their second passage continued this differentiation pattern similar to those in the controls. In conclusion, these results suggest that CDCA can guide mES cells by an FXR-independent pathway to differentiate into ectoderm and/or mesoderm, but not endoderm.

Park, Soon-Jung; Lee, Seul-Bi; Lee, Dong-Sup; Ryu, Young-Joon; Lee, Gene; Cho, Jaejin

2013-01-01

383

Stem Cell and Renal Disease  

Microsoft Academic Search

The renal disease is a common problem in human society. End-stage renal disease is a big heath problem in the United States and in all places of the world. Embryonic stem cells, pluripotent derivatives of the inner cell mass of the blastocyst, are the most primitive cell type likely to find application in cell therapy. Their potential to generate any

Hongbao Ma; Shen Cherng; Yan Yang

2009-01-01

384

Stem cells in the kidney  

Microsoft Academic Search

Stem cells in the kidney. The kidney is derived from the ureteric bud and the metanephrogenic mesenchyme, and these two progenitor cells differentiate into more than 26 different cell types in the adult kidney. The ureteric bud contains the precursor of the epithelial cells of the collecting duct and the renal mesenchyme contains precursors of all the epithelia of the

Qais Al-Awqati; Juan A. Oliver

2002-01-01

385

Renal Stem Cells and Kidney Regeneration  

Microsoft Academic Search

\\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

Takashi Yokoo; Akira Fukui; Kei Matsumoto; Tetsuya Kawamura

386

Mesenchymal stem cells and tooth engineering.  

PubMed

Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration. PMID:20690498