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1

Stem Cells  

MedlinePLUS

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

2

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

3

Embryonic Stem Cell Therapy Shows Long-Term Effectiveness, Safety  

MedlinePLUS

... on this page, please enable JavaScript. Embryonic Stem Cell Therapy Shows Long-Term Effectiveness, Safety In small ... 15, 2014 Related MedlinePlus Pages Macular Degeneration Stem Cells TUESDAY, Oct. 14, 2014 (HealthDay News) -- A new ...

4

Effect of RGD nanospacing on differentiation of stem cells.  

PubMed

Nanopatterns of a cell-adhesive peptide arginine-glycine-aspartate (RGD) on a persistently non-fouling poly(ethylene glycol) hydrogel were prepared, and behaviours of mesenchymal stem cells (MSCs) on patterns of five RGD nanospacings from 37 to 124 nm were examined under a full level of serum for eight days. Besides cell adhesion, osteogenic and adipogenic inductions of MSCs from rat bone marrow were observed in corresponding media. We not only confirmed the nanospacing dependence of cell spreading previously reported in other cell types (non-stem cells) such as less spreading in the case of nanospacings larger than the critical 70 nm, but also found the effect of RGD nanospacing on lineage commitments of stem cells. Both osteogenic and adipogenic inductions resulted in higher differentiation extents on patterns of large nanospacings than of small nanospacings. Under co-induction in the mixed osteogenic/adipogenic media, osteogenesis was predominant over adipogenesis on patterns of large RGD nanospacings, although a less cell spreading itself was beneficial not for osteogenesis but for adipogenesis according to previous studies without nanopatterns. The effect of RGD nanospacing on lineage commitments of stem cells is unexpected and cannot be interpreted via the cell spreading effect. Thus, the differentiation of stem cells might be regulated inherently by nanospacing of bioactive ligands on the material surfaces. PMID:23357372

Wang, Xuan; Yan, Ce; Ye, Kai; He, Yao; Li, Zhenhua; Ding, Jiandong

2013-04-01

5

Stem Cell Basics  

MedlinePLUS

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

6

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. PMID:22216215

Jiang, Yuanda; Hang, Haiying

2011-01-01

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

Cell Stem Cell Stem Cell States, Fates,  

E-print Network

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

Peterson, Carsten

9

Stem cells supporting other stem cells  

PubMed Central

Adult stem cell therapies are increasingly prevalent for the treatment of damaged or diseased tissues, but most of the improvements observed to date are attributed to the ability of stem cells to produce paracrine factors that have a trophic effect on existing tissue cells, improving their functional capacity. It is now clear that this ability to produce trophic factors is a normal and necessary function for some stem cell populations. In vivo adult stem cells are thought to self-renew due to local signals from the microenvironment where they live, the niche. Several niches have now been identified which harbor multiple stem cell populations. In three of these niches – the Drosophila testis, the bulge of the mammalian hair follicle, and the mammalian bone marrow – one type of stem cell has been found to produce factors that contribute to the maintenance of a second stem cell population in the shared niche. In this review, I will examine the architecture of these three niches and discuss the molecular signals involved. Together, these examples establish a new paradigm for stem cell behavior, that stem cells can promote the maintenance of other stem cells. PMID:24348512

Leatherman, Judith

2013-01-01

10

Stem Cells and Diseases  

MedlinePLUS

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

11

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

12

Cancer Stem Cells Implications for Development of More Effective Therapies  

Microsoft Academic Search

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

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

13

Intraoperative Stem Cell Therapy  

PubMed Central

Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

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

2013-01-01

14

Stem Cell Transplants  

MedlinePLUS

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

15

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

Microsoft Academic Search

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

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

2011-01-01

16

Effect of Stem Cell Therapy on Adriamycin Induced Tubulointerstitial Injury  

PubMed Central

Background and Objectives It was postulated that adriamycin (ADR) induce renal tubulointerstitial injury. Clinicians are faced with a challenge in producing response in renal patients and slowing or halting the evolution towards kidney failure. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on tubular renal damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. Methods and Results Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy, vacuolated cytoplasm, dark nuclei, detached epithelial lining and desquamated nuclei were noticed in few collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of CT showing desquamated nuclei and mean value of serum creatinine revealed significant difference in ADR group. The mean area% of Prussian blue+ve cells and that of CD105 +ve cells measured in subgroup S1 denoted a significant increase compared to subgroups S2 and S3. Conclusions ADR induced tubulointerstitial damage that regressed in response to cord blood HMSC therapy. PMID:24298366

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

2012-01-01

17

Alginate-PLL microencapsulation: Effect on the differentiation of embryonic stem cells into hepatocytes  

Microsoft Academic Search

The emergence of hepatocyte based clinical and pharmaceuticaltechnologies,hasbeen limitedbythe absence of a stable hepatocyte cell source. Embryonic stem cells may represent a potential solution to this cell source limitation problem since they are highly proliferative, renewable, and pluripotent. Although many investigators have described techniques to effectively differentiate stem cells into a variety of mature cell lineages, their practicality is limited

Tim Maguire; Eric Novik; Rene Schloss; Martin Yarmush

2006-01-01

18

Hematopoietic stem cell transplantation  

PubMed Central

More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and myeloproliferative syndromes. Before transplantation, patients receive intensive myeloablative chemoradiotherapy followed by stem cell “rescue.” Autologous HSCT is performed using the patient’s own hematopoietic stem cells, which are harvested before transplantation and reinfused after myeloablation. Allogeneic HSCT uses human leukocyte antigen (HLA)-matched stem cells derived from a donor. Survival after allogeneic transplantation depends on donor–recipient matching, the graft-versus-host response, and the development of a graft versus leukemia effect. This article reviews the biology of stem cells, clinical efficacy of HSCT, transplantation procedures, and potential complications. PMID:24198516

Hatzimichael, Eleftheria; Tuthill, Mark

2010-01-01

19

[Peripheral blood stem cell collection from ABO incompatible allogeneic donors and its effect in hematopoietic stem cell transplantation].  

PubMed

The study was aimed to evaluate the yield of the COBE Spectra blood cell separator with auto-peripheral blood stem cell program for collection of peripheral blood hematopoietic stem cells (PBHSC) from HLA-matched ABO-incompatible allogeneic PBHSC donor, and observe the safety and effect of allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBHSCT) without removal of erythrocytes and plasma. PBHSC from 28 allogeneic donors were collected by COBE Spectra blood cell separator with auto-peripheral blood hematopoiEtic stem cell (auto-PBHSCT) program. Control group included 15 HLA-matched patients who received allo-PBHSCT with ABO-compatible grafts. The amount of PBHSC was harvested and the parameter was modified according to the hematocrit and mononuclear cell (MNC) counts of donors. The nucleated cell count, proportion of MNC, number of CD34(+) cells were detected, and reconstitution status of hematopoietic function and time for change into donor's blood group were observed. The results showed that the nucleated cell count proportion of MNC and number of CD34(+) cells showed no significant difference between groups of ABO incompatible and compatible (p > 0.05). All their hematopoietic functions were reconstituted. Between the ABO incompatibility and the compatible groups, the time of neutrophil and platelet recovery was not significantly different (p > 0.05), In ABO blood major incompatible and the compatible groups, the recovery of erythropoiesis were significantly delayed (p < 0.01). The blood type of 18 patients in ABO incompatible group was turned into donor's blood type successfully at 35-139 days after transplantation. It is concluded that major ABO incompatibility did not affect the erythropoiesis reconstitution in HLA matched allo-HSCT. the major incompatibility may be a main reason of erythropoietic delay. PMID:22040979

Xu, Wei; Zhu, Mei; Li, Yan-Ping; Bian, Mao-Hong; Wei, Yu-Zhi; Xia, Xue; Zhang, Xun-Shan

2011-10-01

20

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

PubMed

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

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

2005-06-01

21

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

NASA Astrophysics Data System (ADS)

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

Diop, Rokhaya; Li, Song

22

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. PMID:20635904

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

2011-01-01

23

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

24

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

25

Epithelial Cells Stem Cells  

E-print Network

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

Schüler, Axel

26

Effect of thrombopoietin on peroxidase activity of cryopreserved peripheral blood stem cells  

Microsoft Academic Search

Transplantation of mobilized peripheral blood stem cells is increasingly used to facilitate hematological recovery following high-dose chemotherapy. In general, peripheral blood stem cells can be maintained by cryopreservation, e.g., at -80°C, until the day of transplantation. We investigated the effect of thrombopoietin (c-Mpl ligand) on cryopreserved peripheral blood stem cells obtained from 10 patients with malignant disease by assessing peroxidase

Munehiro Date; Shosaku Nomura; Kaoruko Katsura; Hiroshi Ichiyoshi; Hiroynki Kitajima; Yuji Kishimoto; Takashi Kimura; Shirou Fukuhara

1997-01-01

27

Stem Cell Mobilization with Cyclophosphamide Overcomes the Suppressive Effect of Lenalidomide Therapy on Stem Cell Collection in Multiple Myeloma  

Microsoft Academic Search

A total of 28 treatment-naïve patients with stage II or III multiple myeloma (MM) were treated with the combination of clarithromycin, lenalidomide, and dexamethasone (BiRD). Stem cells were collected following granulocyte-colony stimulating factor (G-CSF) or cyclophosphamide (Cy) plus G-CSF mobilization at maximum response. Sufficient stem cells for 2 autologous stem cell transplants were collected from all patients mobilized with Cy

Tomer Mark; Jessica Stern; Jessica R. Furst; David Jayabalan; Faiza Zafar; April LaRow; Roger N. Pearse; John Harpel; Tsiporah Shore; Michael W. Schuster; John P. Leonard; Paul J. Christos; Morton Coleman; Ruben Niesvizky

2008-01-01

28

Dental Pulp Stem Cells  

Microsoft Academic Search

Postnatal stem cells have been isolated from a variety of tissues. These stem cells are thought to possess great therapeutic potential for repairing damaged and\\/or defective tissues. Clinically, hematopoietic stem cells have been successfully used for decades in the treatment of various diseases and disorders. However, the therapeutic potential of other postnatal stem cell populations has yet to be realized,

He Liu; Stan Gronthos; Songtao Shi

2006-01-01

29

Stem cells in urology  

Microsoft Academic Search

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

Tamer Aboushwareb; Anthony Atala

2008-01-01

30

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

31

Stem Cell Image Library  

NSDL National Science Digital Library

The mission of the Stem Cell Resources website is "to provide timely, reliable, high-quality and scientifically credible stem cell information for the educational community worldwide." This section of their site, the Stem Cell Image Library, presents a collection of microscope images of stem cells in various phases.

2012-11-13

32

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

PubMed Central

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

Jilkine, Alexandra; Gutenkunst, Ryan N.

2014-01-01

33

Cell Stem Cell Clinical Progress  

E-print Network

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

Zandstra, Peter W.

34

Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells  

PubMed Central

Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine. PMID:24710542

Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Shigemoto, Taeko; Dezawa, Mari

2012-01-01

35

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

PubMed Central

Myelosuppression and drug resistance are common adverse effects in cancer patients with chemotherapy, and those severely limit the therapeutic efficacy and lead treatment failure. It is unclear by which cellular mechanism anticancer drugs suppress bone marrow, while drug-resistant tumors survive. We report that due to the difference of glucosylceramide synthase (GCS), catalyzing ceramide glycosylation, doxorubicin (Dox) eliminates bone marrow stem cells (BMSCs) and expands breast cancer stem cells (BCSCs). It was found that Dox decreased the numbers of BMSCs (ABCG2+) and the sphere formation in a dose-dependent fashion in isolated bone marrow cells. In tumor-bearing mice, Dox treatments (5 mg/kg, 6 days) decreased the numbers of BMSCs and white blood cells; conversely, those treatments increased the numbers of BCSCs (CD24?/CD44+/ESA+) more than threefold in the same mice. Furthermore, therapeutic-dose of Dox (1 mg/kg/week, 42 days) decreased the numbers of BMSCs while it increased BCSCs in vivo. Breast cancer cells, rather than bone marrow cells, highly expressed GCS, which was induced by Dox and correlated with BCSC pluripotency. These results indicate that Dox may have opposite effects, suppressing BMSCs versus expanding BCSCs, and GCS is one determinant of the differentiated responsiveness of bone marrow and cancer cells. PMID:22728310

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

2012-01-01

36

The Effect of Bone-Marrow-Derived Stem Cells and Adipose-Derived Stem Cells on Wound Contraction and Epithelization  

PubMed Central

Objective: The relationship between the wound contraction and levels of ?-smooth muscle actin (?-SMA) has been revealed in different studies. We aimed to investigate the effects of mesenchymal stem cells (MSCs), mainly bone-marrow-derived stem cells (BSCs) and adipose-derived stem cells (ASCs), and find out the ?-SMA, fibroblast growth factor (FGF), transforming growth factor beta, and vascular endothelial growth factor (VEGF) levels on an in vivo acute wound healing model after the application of MSCs. Approach: Four circular skin defects were formed on the dorsum of Fisher rats (n=20). The defects were applied phosphate-buffered saline (PBS), ASCs, BSCs, and patchy skin graft, respectively. The healing time and scar area were noted. Results: There was a statistical decrease in the healing time in ASC, BSC, and skin graft groups (p<0.05). However, the scar was smaller in the PBS group (p<0.05). The ?-SMA levels were statistically lower in ASC, BSC, and graft groups (p<0.05). The FGF levels were statistically higher in ASC and BSC groups (p<0.05). The differentiation of the injected MSCs to endothelial cells and keratinocytes was observed. Innovation and Conclusion: MSCs decrease the healing time and contraction of the wound while increasing the epithelization rate by increasing angiogenesis. PMID:24940554

Uysal, Cagri A.; Tobita, Morikuni; Hyakusoku, Hiko; Mizuno, Hiroshi

2014-01-01

37

Stem Cell Biobanks  

Microsoft Academic Search

Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term\\u000a storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific\\u000a clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed\\u000a through biobanking activity, generating a return of investment.

Silvana Bardelli

2010-01-01

38

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

39

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

40

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. PMID:23028757

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

2012-01-01

41

Cell Stem Cell Perspective  

E-print Network

, genetic vari- ations in iPSCs may originate from the heterogeneous genetic makeup of source cell novo variations (Figure 1B). Third, like ESCs, prolonged culturing of iPSCs may introduce or select in in vitro cultured PSCs, including iPSCs and ESCs. One comprehensive study by the International Stem Cell

Zhang, Yi

42

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

EPA Science Inventory

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

43

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

44

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

Microsoft Academic Search

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

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

2010-01-01

45

Effect of epithelial stem cell transplantation on noise-induced hearing loss in adult mice.  

PubMed

Noise trauma in mammals can result in damage to multiple epithelial cochlear cell types, producing permanent hearing loss. Here we investigate whether epithelial stem cell transplantation can ameliorate noise-induced hearing loss in mice. Epithelial stem/progenitor cells isolated from adult mouse tongue displayed extensive proliferation in vitro as well as positive immunolabelling for the epithelial stem cell marker p63. To examine the functional effects of cochlear transplantation of these cells, mice were exposed to noise trauma and the cells were transplanted via a lateral wall cochleostomy 2 days post-trauma. Changes in auditory function were assessed by determining auditory brainstem response (ABR) threshold shifts 4 weeks after stem cell transplantation or sham surgery. Stem/progenitor cell transplantation resulted in a significantly reduced permanent ABR threshold shift for click stimuli compared to sham-injected mice, as corroborated using two distinct analyses. Cell fate analyses revealed stem/progenitor cell survival and integration into suprastrial regions of the spiral ligament. These results suggest that transplantation of adult epithelial stem/progenitor cells can attenuate the ototoxic effects of noise trauma in a mammalian model of noise-induced hearing loss. PMID:21059389

Sullivan, Jeremy M; Cohen, Mauricio A; Pandit, Sonali R; Sahota, Raguwinder S; Borecki, Alexander A; Oleskevich, Sharon

2011-02-01

46

Cell Stem Cell Brief Report  

E-print Network

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

Church, George M.

47

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

48

Cell Fusion and Stem Cells  

Microsoft Academic Search

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

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

49

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

50

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

PubMed Central

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

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

2014-01-01

51

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

PubMed

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

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

2014-08-01

52

Cell Stem Cell Stem Cell Epigenetics: Looking Forward  

E-print Network

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

Sander, Maike

53

Cell Stem Cell Control of Stem Cell Fate by Physical  

E-print Network

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

Chen, Christopher S.

54

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

55

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

Microsoft Academic Search

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

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

1983-01-01

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. PMID:20882496

Lutolf, Matthias P.; Blau, Helen M.

2011-01-01

57

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

58

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. PMID:20811157

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

2010-01-01

59

Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells.  

PubMed

Pluripotent stem cells hold great promises for regenerative medicine. They might become useful as a universal source for a battery of new cell replacement therapies. Among the major concerns for the clinical application of stem cell-derived grafts are the risks of immune rejection and tumor formation. Pluripotency and tumorigenicity are closely linked features of pluripotent stem cells. However, the capacity to form teratomas or other tumors is not sufficiently described by inherited features of a stem cell line or a stem cell-derived graft. The tumorigenicity always depends on the inability of the recipient to reject the tumorigenic cells. This review summarizes recent data on the tumorigenicity of pluripotent stem cells in immunodeficient, syngeneic, allogeneic, and xenogeneic hosts. The effects of immunosuppressive treatment and cell differentiation are discussed. Different immune effector mechanisms appear to be involved in the rejection of undifferentiated and differentiated cell populations. Elements of the innate immune system, such as natural killer cells and the complement system, which are active also in syngeneic recipients, appear to preferentially reject undifferentiated cells. This effect could reduce the risk of tumor formation in immunocompetent recipients. Cell differentiation apparently increases susceptibility to rejection by the adaptive immune system in allogeneic hosts. The current data suggest that the immune system of the recipient has a major impact on the outcome of pluripotent stem cell transplantation, whether it is rejection, engraftment, or tumor development. This has to be considered when the results of experimental transplantation models are interpreted and even more when translation into clinics is planned. PMID:21461989

Dressel, Ralf

2011-11-01

60

Effects of low-intensity pulsed ultrasound on cell viability, proliferation and neural differentiation of induced pluripotent stem cells-derived neural crest stem cells.  

PubMed

Low-intensity pulsed ultrasound (LIPUS) acting on induced pluripotent stem cells-derived neural crest stem cells (iPSCs-NCSCs) is considered a promising therapy to improve the efficacy of injured peripheral nerve regeneration. Effects of LIPUS on cell viability, proliferation and neural differentiation of iPSCs-NCSCs were examined respectively in this study. LIPUS at 500 mW cm(-2) enhanced the viability and proliferation of iPSCs-NCSCs after 2 days and, after 4 days, up-regulated gene and protein expressions of NF-M, Tuj1, S100? and GFAP in iPSCs-NCSCs whereas after 7 days expression of only NF-M, S100? and GFAP were up-regulated. LIPUS treatment at an appropriate intensity can, therefore, be an efficient and cost-effective method to enhance cell viability, proliferation and neural differentiation of iPSCs-NCSCs in vitro for peripheral nerve tissue engineering. PMID:24078117

Lv, Yonggang; Zhao, Pengcheng; Chen, Guobao; Sha, Yongqiang; Yang, Li

2013-12-01

61

Stem Cell 101 What is a stem cell?  

E-print Network

and stem cells found in the skin generally form skin. However, some research suggests that certain adultStem Cell 101 What is a stem cell? A stem cell is a parent cell in the body that has two specific into all types of tissue in the body ­ this is called differentiation. Where are stem cells found

Minnesota, University of

62

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

63

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

PubMed

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

Das, Rajat K; Zouani, Omar F

2014-07-01

64

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

65

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

PubMed

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

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

2014-02-01

66

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

Microsoft Academic Search

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

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

2005-01-01

67

Stem cells and reproduction  

PubMed Central

Purpose of review To review the latest developments in reproductive tract stem cell biology. Recent findings In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cyropreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. Summary Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent. PMID:20305558

Du, Hongling; Taylor, Hugh S.

2011-01-01

68

The effect of stromal cell-derived factor 1 in the migration of neural stem cells.  

PubMed

Neural stem cells (NSCs) have widely been used in the treatment of human neurological disorders as cell therapy via intracerebral or intraventricular infusion. However, the migration mechanism required for NSCs homing and recruitment remains to be elucidated. Recently, SDF-1/CXCR4 axis was shown to be responsible for in cell migration and differentiation during the neural development stage and involved in the pathophysiological process of neurological disorders. In this study, we investigated the effect of SDF-1 in migration of NSCs in vitro and in vivo. The expression of CXCR4 receptor was examined by immunocytochemistry and RT-PCR. The migratory ability of NSCs induced by SDF-1 was assessed by transwell chemotaxis assay. The traumatic brain injury rat model was well established, and the recruitment of NSCs and expression of SDF-1 were investigated in vivo. Our findings demonstrated that SDF-1, in vitro, significantly induced the migratory of NSCs in a dose-dependent manner. An overexpression of neural stem cell marker Nestin in the hippocampus was observed after TBI, and the expressions of SDF-1 surrounding the lesion areas were significantly increased. Our results suggested that the migration of NSCs was activated by chemotactic effect of SDF-1. It was also proved the relevance of SDF-1 in the migration of endogenous NSCs after brain injury. Taken together, these results demonstrated that SDF-1/CXCR4 axis may play crucial role in the migration of Nestin-positive cell after brain injury. PMID:25241080

Xue, Liping; Wang, Jinkun; Wang, Weimin; Yang, Zhiyong; Hu, Zhulin; Hu, Min; Ding, Peng

2014-12-01

69

Bioreactors Stem Cells  

E-print Network

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

Schüler, Axel

70

Stem Cell Resources  

NSDL National Science Digital Library

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

71

Stem cells in pharmaceutical biotechnology.  

PubMed

Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All together, the applications of various cell types derived from patient specific pluripotent stem cells may lead to targeted drug and cellular therapies for certain individuals. PMID:21902635

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

2011-11-01

72

Effect of cell density on adipogenic differentiation of mesenchymal stem cells  

SciTech Connect

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

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

2009-04-10

73

"Mesenchymal" stem cells.  

PubMed

Two opposing descriptions of so-called mesenchymal stem cells (MSCs) exist at this time. One sees MSCs as the postnatal, self-renewing, and multipotent stem cells for the skeleton. This cell coincides with a specific type of bone marrow perivascular cell. In skeletal physiology, this skeletal stem cell is pivotal to the growth and lifelong turnover of bone and to its native regeneration capacity. In hematopoietic physiology, its role as a key player in maintaining hematopoietic stem cells in their niche and in regulating the hematopoietic microenvironment is emerging. In the alternative description, MSCs are ubiquitous in connective tissues and are defined by in vitro characteristics and by their use in therapy, which rests on their ability to modulate the function of host tissues rather than on stem cell properties. Here, I discuss how the two views developed, conceptually and experimentally, and attempt to clarify the confusion arising from their collision. PMID:25150008

Bianco, Paolo

2014-10-11

74

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

PubMed

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

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

2014-01-01

75

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. PMID:18187050

Oertel, Michael; Shafritz, David A.

2008-01-01

76

Stem cell therapy for osteoporosis.  

PubMed

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

Antebi, Ben; Pelled, Gadi; Gazit, Dan

2014-03-01

77

Stem cell therapy without the cells  

PubMed Central

As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells1 instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.2 We most often think of stem cell therapy acting to regenerate tissue through replication and then differentiation, but recent studies point to the dramatic effects adult stem cells exert in the repair of various tissues through the release of paracrine and autocrine substances, and not simply through differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells has been shown to be through paracrine mediated actions.3 That is, the collected types of molecules released by the stem cells, called the secretome, or stem cell released molecules (SRM), number in the 100s, including proteins, microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a multitude of biological pathways through paracrine actions. The composition of the different molecule types in SRM is state dependent, and varies with cell type and conditions such as age and environment. PMID:24567776

Maguire, Greg

2013-01-01

78

Stem cells in dermatology*  

PubMed Central

Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today. PMID:24770506

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

2014-01-01

79

Stem cells and brain cancer  

Microsoft Academic Search

An increasing body of research is showing that cancers might contain their own stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a deregulated cellular self-renewal capacity. This raises the possibility that some features of tumor cells may be due to cancer stem cells. Stem cell-like cancer cells were isolated from several solid tumors. Now, evidence

U Galderisi; M Cipollaro; A Giordano

2006-01-01

80

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. PMID:24147217

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

2013-01-01

81

Cell Stem Cell Dear Student: Stem Cell Scientists' Advice  

E-print Network

a career in stem cell research?'' ``Besides lending great worth to a scholar's life, leaving spiritual prog or restrict certain types of stem cell research raised profound questions about the field's sustainability. In academia, stem cell research has quickly become institutionalized. Research universities seized the opportu

82

p53 in stem cells  

PubMed Central

p53 is well known as a “guardian of the genome” for differentiated cells, in which it induces cell cycle arrest and cell death after DNA damage and thus contributes to the maintenance of genomic stability. In addition to this tumor suppressor function for differentiated cells, p53 also plays an important role in stem cells. In this cell type, p53 not only ensures genomic integrity after genotoxic insults but also controls their proliferation and differentiation. Additionally, p53 provides an effective barrier for the generation of pluripotent stem cell-like cells from terminally differentiated cells. In this review, we summarize our current knowledge about p53 activities in embryonic, adult and induced pluripotent stem cells. PMID:21949570

Solozobova, Valeriya; Blattner, Christine

2011-01-01

83

Autophagy in stem cells  

PubMed Central

Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future. PMID:23486312

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

2013-01-01

84

Effects of biologic scaffolds on human stem cells and implications for CNS tissue engineering.  

PubMed

Biologic scaffolds composed of mammalian extracellular matrix (ECM) promote constructive remodeling of tissues via mechanisms that include the recruitment of endogenous stem/progenitor cells, modulation of the host innate immune response, and influence of cell fate differentiation. Such scaffold materials are typically prepared by decellularization of source tissues and are prepared as sheets, powder, or hydrogels. It is plausible that ECM derived from an anatomically distinct tissue would have unique or specific effects on cells that naturally reside in this same tissue. The present study investigated the in vitro effect of a soluble form of ECM derived from central nervous system (CNS) tissue, specifically the spinal cord or brain, versus ECM derived from a non-CNS tissue; specifically, the urinary bladder on the behavior of neural stem cells (NSCs) and perivascular stem cells. All forms of ECM induce positive, mitogenic, and chemotactic effects at concentrations of approximately 100 ?g/mL without affecting stem cell viability. CNS-derived ECMs also showed the ability to differentiate NSCs into neurons as indicted by ?III-tubulin expression in two-dimensional culture and neurite extension on the millimeter scale after 24 days of three-dimensional cultures in an ECM hydrogel. These results suggest that solubilized forms of ECM scaffold materials may facilitate the postinjury healing response in CNS tissues. PMID:24004192

Crapo, Peter M; Tottey, Stephen; Slivka, Peter F; Badylak, Stephen F

2014-01-01

85

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

Microsoft Academic Search

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

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

2008-01-01

86

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

PubMed

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

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

2014-05-01

87

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

PubMed Central

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

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

2014-01-01

88

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

NASA Technical Reports Server (NTRS)

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

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

2003-01-01

89

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

90

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.

91

Effects of hesperetin on vessel structure formation in mouse embryonic stem (mES) cells  

Microsoft Academic Search

ObjectiveThe present study investigated the effects of hesperetin on vessel structure formation in mouse embryonic stem (mES) cells with regard to whether hesperetin acts as an antioxidant or pro-oxidant. Some flavonoids enhance antioxidant systems while increasing oxidative stress in the body.

Eun Jeong Choi; Gi Dae Kim; Kew-Mahn Chee; Gun-Hee Kim

2006-01-01

92

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

E-print Network

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

Voldman, Joel

93

The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation  

PubMed Central

Background: Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. Materials and Methods: In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. Results: In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. Conclusion: This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications. PMID:25337532

Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

2014-01-01

94

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. PMID:14614776

Chen, Jennifer CJ; Goldhamer, David J

2003-01-01

95

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. PMID:22615926

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

2012-01-01

96

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

97

Information on Stem Cell Research  

MedlinePLUS

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

98

LESSON PLAN Stem Cell Discussion  

E-print Network

of stem cell research · research the current research situation · debate the future of stem cell of the ethical, moral and social implications of stem cell research. Photocopy these pages and distribute to students to read. · Make a list of advantages and disadvantages of using embryonic stem cells in research

Rambaut, Andrew

99

Haute Culture: Tailoring stem cells  

E-print Network

Biology, Department of Stem Cell and Regenerative Biology, Harvard University Massachusetts General Hospital Fernando Camargo, PhD Assistant Professor of Stem Cell Regenerative Biology, Department of Stem Cell and Regenerative Biology, Harvard University Children's Hospital Boston Stem Cell Program #12

Chou, James

100

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. PMID:24077523

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

2013-01-01

101

Germline Stem Cells  

PubMed Central

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

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

2011-01-01

102

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

103

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

104

Effect of Stem Cell Therapy on Induced Diabetic Keratopathy in Albino Rat  

PubMed Central

Background and Objectives: Type 2 diabetes mellitus (DM) is a prevalent disorder. Diabetic keratopathy is a well-known ocular complication secondary to type 2 DM. Topical insulin application did not affect apoptosis and necrosis levels in corneal epithelium. Autologous cell transplantation is not a viable option for diabetic patients with bilateral limbal stem cell deficiency. The present study aimed at assessing the possible effect of hemopoeitic stem cell (HSC) therapy on induced diabetic keratopathy in albino rat. Methods and Results: Fifteen male albino rats were divided into control group of 2 rats, diabetic group of 8 rats receiving single intraperitoneal (IP) injection of 50 mg/kg streptozotocin (STZ). 3 animals were sacrificed 6 weeks following confirmation of diabetes to confirm keratopathy and 5 rats were sacrificed 4 weeks following confirmation of keratopathy. SC therapy group included 5 rats injected with HSCs 6 weeks following confirmation of diabetes and sacrificed 4 weeks following SC therapy. Cord blood collection, stem cells isolation and labeling were performed. Eye specimens were subjected to histological, histochemical, immunohistochemical, morphometric and statistical studies. In diabetic group, the central cornea showed multiple cells with vacuolated cytoplasm and dark nuclei, focal epithelial discontinuity, reduced corneal thickness and less number of layers of corneal and conjunctival epithelia. In stem cell therapy group, few cells with vacuolated cytoplasm and dark nuclei were found in the corneal and conjunctival epithelia with more number of epithelial layers. Conclusions: A definite ameliorating effect of HSC therapy was detected on diabetic keratopathy. The therapeutic cells were effective in limiting corneal epithelial changes. PMID:24298355

Zickri, Maha Baligh; Ahmad, Nagwa Abdel Wahab; Maadawi, Zeinab Mohamad El; Mohamady, Yasmin Kamal; Metwally, Hala Gabr

2012-01-01

105

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

PubMed Central

The roles of limbal epithelial stem cells (LESCs) are widely recognized, but for these cells to be utilized in basic research and potential clinical applications, researchers must be able to efficiently isolate them and subsequently maintain their stemness in vitro. We aimed to develop a biomimetic environment for LESCs involving cells from their in vivo niche and the principle of flow-induced shear stress, and to subsequently demonstrate the potential of this novel paradigm. LESCs, together with neighboring cells, were isolated from the minced limbal tissues of rabbits. At days 8 and 9 of culture, the cells were exposed to a steady flow or intermittent flow for 2 h per day in a custom-designed bioreactor. The responses of LESCs and epithelial cells were assessed at days 12 and 14. LESCs and epithelial cells responded to both types of flow. Proliferation of LESCs, as assessed using a BrdU assay, was increased to a greater extent under steady flow conditions. Holoclones were found under intermittent flow, indicating that differentiation into transient amplifying cells had occurred. Immunofluorescent staining of Bmi-1 suggested that steady flow has a positive effect on the maintenance of stemness. This finding was confirmed by real-time PCR. Notch-1 and p63 were more sensitive to intermittent flow, but this effect was transient. K3 and K12 expression, indicative of differentiation of LESCs into epithelial cells, was induced by flow and lasted longer under intermittent flow conditions. In summary, culture of LESCs in a bioreactor under a steady flow paradigm, rather than one of intermittent flow, is beneficial for both increasing proliferation and maintaining stemness. Conversely, intermittent flow appears to induce differentiation of LESCs. This novel experimental method introduces micro-mechanical stimuli to traditional culture techniques, and has potential for regulating the proliferation and differentiation of LESCs in vitro, thereby facilitating research in this field. PMID:24658122

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

2014-01-01

106

Cell Stem Cell Short Article  

E-print Network

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

Collins, James J.

107

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. PMID:23617463

2013-01-01

108

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

Microsoft Academic Search

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

Yasuyuki Amoh; Kensei Katsuoka; Robert M. Hoffman

2010-01-01

109

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

PubMed Central

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

Zhang, Jianying; Wang, James H-C.

2014-01-01

110

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

PubMed

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

Zhang, Jianying; Wang, James H-C

2014-01-01

111

Encapsulated stem cells for cancer therapy.  

PubMed

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

Shah, Khalid

2013-01-01

112

Encapsulated stem cells for cancer therapy  

PubMed Central

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

2013-01-01

113

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

2012-10-01

114

Effects of the polymeric niche on neural stem cell characteristics during primary culturing.  

PubMed

The polymeric niche encountered by cells during primary culturing can affect cell fate. However, most cell types are primarily propagated on polystyrene (PS). A cell type specific screening for optimal primary culture polymers particularly for regenerative approaches seems inevitable. The effect of physical and chemical properties of treated (corona, oxygen/nitrogen plasma) and untreated cyclic olefin polymer (COP), polymethymethacrylate (PMMA), PP, PLA, PS, PC on neuronal stem cell characteristics was analyzed. Our comprehensive approach revealed plasma treated COP and PMMA as optimal polymers for primary neuronal stem cell culturing and propagation. An increase in the number of NT2/D1 cells with pronounced adhesion, metabolic activities and augmented expression of neural precursor markers was associated to the plasma treatment of surfaces of COP and PMMA with nitrogen or oxygen, respectively. A shift towards large cell sizes at stable surface area/volume ratios that might promote the observed increase in metabolic activities and distinct modulations in F-actin arrangements seem to be primarily mediated by the plasma treatment of surfaces. These results indicate that the polymeric niche has a distinct impact on various cell characteristics. The selection of distinct polymers and the controlled design of an optimized polymer microenvironment might thereby be an effective tool to promote essential cell characteristics for subsequent approaches. PMID:24577943

Haubenwallner, Stefan; Katschnig, Matthias; Fasching, Ulrike; Patz, Silke; Trattnig, Christa; Andraschek, Natascha; Grünbacher, Gerda; Absenger, Markus; Laske, Stephan; Holzer, Clemens; Balika, Werner; Wagner, Manuela; Schäfer, Ute

2014-05-01

115

Stem Cell Research  

SciTech Connect

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

Verfaillie, Catherine (University of Minnesota) [University of Minnesota

2002-01-23

116

Anticancer effects of cinnamic acid in lung adenocarcinoma cell line h1299-derived stem-like cells.  

PubMed

Lung cancer is a lethal solid tumor with poor prognosis because of its high metastasis and resistance to current therapies. Recently, cancer stem cells (CSCs) were suggested to be major contributors to tumorigenicity and cancer relapse. However, therapeutic targets for lung cancer-related CSCs remain undetermined. The objective of the current study was to investigate whether cinnamic acid (CINN) exerts an antitumor activity against sphere-derived lung CSCs. In this study, CSCs were isolated from the non-small cell lung cancer cell line H1299 as tumor spheres under CSC-selective conditions, and found to have increased tumorigenicity, chemoresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared with parental cells. These observations are consistent with the notion that CSCs are tumorigenic, display the ability to self-renew, and generate differentiated progeny that constitute the majority of cells in tumors. Treatment of sphere-derived stem cells with CINN could diminish their CSC-like abilities by decreasing their proliferation and invasive abilities and facilitating their differentiation into CD133-negative cells. Furthermore, CINN treatment increased the sensitivity of CSCs to chemotherapeutic drugs through apoptosis. Of note, xenotransplantation experiments revealed that CINN combined with cisplatin had a synergistic effect in inhibiting the tumorigenicity of CSCs. In summary, our study clearly revealed the presence of a population of sphere-forming cells with stem-like properties among H1299 cells and CINN can attenuate CSC properties of this stem-like cell population. The potential of CINN should be verified further in future studies of anti-CSC therapy. PMID:24063280

Huang, Yanyan; Zeng, Fang; Xu, Liyun; Zhou, Jihang; Liu, Xiaoguang; Le, Hanbo

2013-01-01

117

Stem Cells Branch Out  

NSDL National Science Digital Library

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

Pamela Hines (AAAS;); Beverly Purnell (AAAS;); Jean Marx (AAAS;)

2000-02-25

118

Update on stem cell \\  

Microsoft Academic Search

Summary  Allogeneic haematopoietic stem cell transplantation in humans results in true biological chimeras. Whilst circulating haematopoietic\\u000a cells become donor genotype after transplantation, other cells believed to remain recipient in origin. It was only recently\\u000a realized that bone marrow-derived cells may also contribute to non-haematopoietic tissues, suggesting a level of plasticity\\u000a not previously expected. New concepts in ontogenesis and developmental potential of

A. Spyridonidis

2010-01-01

119

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

120

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. PMID:22399855

Hoover-Plow, Jane; Gong, Yanqing

2012-01-01

121

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

PubMed Central

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

Shakoori, AR; Ahmad, A

2013-01-01

122

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 Central

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

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

2013-01-01

123

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

2013-03-01

124

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

PubMed Central

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

Zhang, Joy Yueyue

2013-01-01

125

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

2012-01-01

126

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?. PMID:21955520

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

2011-01-01

127

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

128

Retracted: Effects of pro-inflammatory cytokines on mineralization potential of rat dental pulp stem cells  

Microsoft Academic Search

The following article from the Journal of Tissue Engineering and Regenerative Medicine, 'Effects of Pro-inflammatory Cytokines on Mineralization Potential of Rat Dental Pulp Stem Cells' by Yang X, Walboomers XF, Bian Z, Jansen JA, Fan M, published online on 11 July 2011 in Wiley Online Library (onlinelibrary.wiley.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, and John

X. Yang; X. F. Walboomers; Z. Bian; J. A. Jansen; M. Fan

2011-01-01

129

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

PubMed

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

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

2014-04-11

130

Blood and Marrow Stem Cell Transplant  

MedlinePLUS

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

131

The Effect of TNF- alpha On The Odontogenic Potential Of Human Dental Stem Cells  

E-print Network

?  on  Human  Dental   Pulp.  Journal  of  Endodontics,  of  Dental  Follicle  Stem  Cells.  International  Journal  dental  pulp  and  periodontal  ligament:  new  prospects  in   dentistry.  International  Journal  

Tseng, Edward

2012-01-01

132

Stem cell therapy in ischemic heart disease.  

PubMed

Coronary artery disease (CAD) remains the leading cause of death in the Western world. The high impact of its main sequelae, acute myocardial infarction and congestive heart failure (CHF), on the quality of life of patients and the cost of health care drives the search for new therapies. The recent finding that stem cells contribute to neovascularization and possibly improve cardiac function after myocardial infarction makes stem cell therapy the most highly active research area in cardiology. Although the concept of stem cell therapy may revolutionize heart failure treatment, several obstacles need to be addressed. To name a few: 1) Which patient population should be considered for stem cell therapy? 2) What type of stem cell should be used? 3) What is the best route for cell delivery? 4) What is the optimum number of cells that should be used to achieve functional effects? 5) Is stem cell therapy safer and more effective than conventional therapies? The published studies vary significantly in design, making it difficult to draw conclusions on the efficacy of this treatment. For example, different models of ischemia, species of donors and recipients, techniques of cell delivery, cell types, cell numbers and timing of the experiments have been used. However, these studies highlight the landmark concept that stem cell therapy may play a major role in treating cardiovascular diseases in the near future. It should be noted that stem cell therapy is not limited to the treatment of ischemic cardiac disease. Non-ischemic cardiomyopathy, peripheral vascular disease, and aging may be treated by stem cells. Stem cells could be used as vehicle for gene therapy and eliminate the use of viral vectors. Finally, stem cell therapy may be combined with pharmacological, surgical, and interventional therapy to improve outcome. Here we attempt a systematic overview of the science of stem cells and their effects when transplanted into ischemic myocardium. PMID:14647535

Sunkomat, Julia N E; Gaballa, Mohamed A

2003-01-01

133

Stem Cells in Intraepithelial Neoplasia  

Microsoft Academic Search

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

Nicholas A. Wright

134

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

PubMed

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

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

2014-02-01

135

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

136

Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells  

PubMed Central

The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo. PMID:19513108

Wagner, Wolfgang; Bork, Simone; Horn, Patrick; Krunic, Damir; Walenda, Thomas; Diehlmann, Anke; Benes, Vladimir; Blake, Jonathon; Huber, Franz-Xaver; Eckstein, Volker; Boukamp, Petra; Ho, Anthony D.

2009-01-01

137

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

PubMed

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

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

2014-01-01

138

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

PubMed Central

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

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

2014-01-01

139

Effects of neuroinflammation on the regenerative capacity of brain stem cells.  

PubMed

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 lipopolysaccharide-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. PMID:21198642

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2011-03-01

140

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. PMID:21198642

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2012-01-01

141

From stem cells to germ cells and from germ cells to stem cells  

Microsoft Academic Search

Germline and somatic stem cells are distinct types of stem cells that are dedicated to reproduction and somatic tissue regeneration, respectively. Germline stem cells (GSCs), which can self-renew and generate gametes, are unique stem cells in that they are solely dedicated to transmit genetic information from generation to generation. We developed a strategy for the establishment of germline stem cell

Gerald Wulf; Ingrid E. Ehrmann; David Elliott; Ulrich Zechner; Thomas Haaf; Andreas Meinhardt; Hans W. Michelmann; Gerlad Hasenfuss; Kaomei Guan

142

Stem Cells and Female Reproduction  

PubMed Central

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

Du, Hongling; Taylor, Hugh S.

2011-01-01

143

Effects of cryopreservation on human mesenchymal stem cells attached to different substrates.  

PubMed

There is a need to preserve cell-seeded scaffolds or cell-matrix constructs for tissue-engineering and other applications. Cryopreservation is likely to be the most practical method. The aim of this study was to investigate how cryopreservation affects cells attached to different substrates and how they respond differently from those in suspension. Human mesenchymal stem cells (hMSCs) were studied for their close relevance to tissue-engineering and stem cell therapy applications, in particular how cryopreservation affects cell adherence, cell growth and the viability of hMSCs attached to different substrates, including glass, gelatin, matrigel and a matrigel sandwich. The effects of cryopreservation on F-actin organization, intracellular pH and mitochondrial localization of the adherent hMSCs were further investigated. It was found that cells attached to a glass surface could hardly survive the common cryopreservation protocol using 10% DMSO and a 1°C/min cooling rate. By contrast, cells attached to gelatin and matrigel could survive to a greater extent. Furthermore, cryopreservation affected the potential of cell attachment and proliferation, resulted in distortion of F-actin, led to alteration of intracellular pH of the hMSCs for all tested substrates and caused a change in the mitochondrial localization of hMSCs on a matrigel substrate and in a matrigel sandwich. Our results showed that cell attachment and cell viability could be improved by changing the interaction between cell and substrate through modification of the substrate properties, which has implications for scaffold design if cell-seeded scaffolds or engineered tissues need to be cryopreserved. PMID:25066447

Xu, Xia; Liu, Yang; Cui, Zhan Feng

2014-08-01

144

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

145

Embryonic Stem Cells  

NSDL National Science Digital Library

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

Erdmann, Deanne; Marx, Joseph; Moreno, Nancy

2006-07-20

146

Inflammation and cancer stem cells.  

PubMed

Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche. PMID:23941828

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

2014-04-10

147

Cell Stem Cell The Systematic Production  

E-print Network

Cell Stem Cell Review The Systematic Production of Cells for Cell Therapies Daniel C. Kirouac1 10.1016/j.stem.2008.09.001 Stem cells have emerged as the starting material of choice for bioprocesses to produce cells and tissues to treat degenerative, genetic, and immunological disease

Zandstra, Peter W.

148

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

NASA Technical Reports Server (NTRS)

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

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

2005-01-01

149

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

PubMed

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

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

2014-01-01

150

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

151

Materials as stem cell regulators  

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

152

Materials as stem cell regulators  

PubMed Central

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

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

2014-01-01

153

Melanoma Stem Cells  

Microsoft Academic Search

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

Tobias Schatton; Markus H. Frank

154

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

155

PEDF & Stem Cells: Niche vs. Nurture.  

PubMed

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

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

2014-01-01

156

Effect of preeclampsia on umbilical cord blood hematopoietic progenitor-stem cells  

Microsoft Academic Search

Objective: The aim of the present study was to determine the influence of preeclampsia on cord blood hematopoietic progenitor-stem cells obtained at delivery because cord blood is increasingly used clinically for stem cell retrieval as an alternative to bone marrow. Study Design: Umbilical cord blood was collected from patients fulfilling the criteria for preeclampsia and from gestational age– and birth

Daniel V. Surbek; Enrico Danzer; Christian Steinmann; André Tichelli; Aleksandra Wodnar-Filipowicz; Sinuhe Hahn; Wolfgang Holzgreve

2001-01-01

157

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

PubMed Central

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

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

2014-01-01

158

Defining Vascular Stem Cells  

PubMed Central

Mesenchymal stem cells (MSCs) exist in most adult tissues and have been located near or within blood vessels. Although “perivascular” has been commonly used to describe such locations, increasing evidence points at the vessel wall as the exact location. Thus, “vascular stem cells (VSCs)” is recommended as a more accurate term for MSCs. Furthermore, 2 cell populations, namely pericytes and adventitial progenitor cells (APCs), are the likely VSCs. The pericyte evidence relies on the so-called pericyte-specific markers, but none of these markers is pericyte specific. In addition, pericytes appear to be too functionally diverse and sophisticated to have a large differentiation capacity. On the other hand, APCs are more naïve functionally and, therefore, more akin to being VSCs. In vitro, these cells spontaneously differentiate into pericytes, and can be induced to differentiate into vascular cells (endothelial and smooth muscle cells) and mesenchymal cells (eg, bone, cartilage, and fat). In vivo, indirect evidence also points to their ability to differentiate into mesenchymal cells of their native tissue (eg, fat). Moreover, they possess a large paracrine capacity and, therefore, can help maintain tissue homeostasis by encouraging the replication and differentiation of mesenchymal cells locally. These proposed in vivo functions are areas of interest for future research on VSCs. PMID:23330734

Lue, Tom F.

2013-01-01

159

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

PubMed Central

Background: Antidepressant drugs are commonly employed for anxiety and mood disorders. Sertraline is extensively used as antidepressant in clinic. In addition, adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human adipose-derived stem cells (hADSCs) may be useful for autologous transplantation. Materials and Methods: In the present study, we assessed the effect of antidepressant drug Sertraline on the proliferation and neurogenic differentiation of hADSCs using MTT assay and immunofluorescence technique respectively. Results: MTT assay analysis showed that 0.5 ?M Sertraline significantly increased the proliferation rate of hADSCs induced cells (P < 0.05), while immunofluorescent staining indicated that Sertraline treatment during neurogenic differentiation could be decreased the percentage of glial fibrillary acidic protein and Nestin-positive cells, but did not significantly effect on the percentage of MAP2 positive cells. Conclusion: Overall, our data show that Sertraline can be promoting proliferation rate during neurogenic differentiation of hADSCs after 6 days post-induction, while Sertraline inhibits gliogenesis of induced hADSCs. PMID:24800186

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

2014-01-01

160

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. PMID:23862141

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

2013-01-01

161

Melanocytes, melanocyte stem cells, and melanoma stem cells  

PubMed Central

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

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

2012-01-01

162

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

PubMed

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

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

2014-06-27

163

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

E-print Network

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

Millman, Jeffrey Robert

2011-01-01

164

Cell Stem Cell Alternative Induced Pluripotent  

E-print Network

-disease- relevant area of stem cell research. We agree that criteria and standards are important to allow for crossCell Stem Cell Letter Alternative Induced Pluripotent Stem Cell Characterization Criteria Cell Facility, SickKids Research Institute, University of Toronto, Toronto, Ontario M5G 1L7, Canada 2

Zandstra, Peter W.

165

Immune effects of mesenchymal stem cells: implications for Charcot-Marie-Tooth disease.  

PubMed

Mesenchymal stem cell (MSC) therapy is the most clinically advanced form of cell therapy, second to hematopoietic stem cell transplants. To date, MSC have been used for immune modulation in conditions such as Graft Versus Host Disease (GVHD) and Crohn's Disease, for which Phase III clinical trials are currently in progress. Here, we review the immunological properties of MSC and make a case for their use in treatment of Charcot-Marie-Tooth disease type 1 (CMT1), a group of inherited peripheral neuropathies. CMT1 is characterized by demyelination and aberrant immune activation making this condition an ideal target for exploration of MSC therapy, given the ability of these cells to promote sheath regeneration as well as suppress inflammation. Studies supporting this hypothesis will be presented and placed into the context of other cell-based approaches that are theoretically feasible. Given that MSCs selectively home to areas of inflammation, as well as exert effects in an allogeneic manner, the possibility of an "off the shelf" therapy for CMT1 will be discussed. PMID:18627903

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

2008-01-01

166

Salivary Gland Cancer Stem Cells  

PubMed Central

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; Nor, Jacques E.

2013-01-01

167

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

PubMed Central

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

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

2013-01-01

168

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

PubMed Central

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

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

2014-01-01

169

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

PubMed Central

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

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

2014-01-01

170

Stem Cell Transplant  

Microsoft Academic Search

\\u000a Hematopoietic stem cell transplant (HSCT) began in humans in the late 1950s and since that time more than 800,000 people have\\u000a been treated with this procedure. To date 150,000 patients are living 5 years or more post transplant, with this number expanding\\u000a rapidly [1]. As advances have been made in refining HSCT and making it more accessible, a larger proportion

Jean C. Yi; Karen L. Syrjala

171

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

172

Developmental Cell Sox2+ Stem Cells Contribute  

E-print Network

as a marker for the dental epithelial stem cells will facilitate further studies on their lineage segregationDevelopmental Cell Article Sox2+ Stem Cells Contribute to All Epithelial Lineages of the Tooth via and Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity

Klein, Ophir

173

Embryonic Stem Cells Cell Signalling Course  

E-print Network

Embryonic Stem Cells Cell Signalling Course Ceské Budjovice January 2013 #12;Pluripotent (stem) cells (Embryonic, Adult, Induced,...?) Promise for biomedicine ·Replacement therapy ·Drug development(s) of differentiation ·Symmetric/asymmetric division ? ? ? ? #12;Where can we find the origins of stem cell research

South Bohemia, University of

174

Embryonic Stem Cells Cell Signalling Course  

E-print Network

Embryonic Stem Cells Cell Signalling Course Ceské Budjovice November 2013 #12;Pluripotent (stem) cells (Embryonic, Adult, Induced,...?) Promise for biomedicine ·Replacement therapy ·Drug development(s) of differentiation ·Symmetric/asymmetric division ? ? ? ? #12;Where can we find the origins of stem cell research

South Bohemia, University of

175

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

176

Background Information 1. What are stem cells?  

E-print Network

Background Information 1. What are stem cells? 2. What might stem cell research achieve? 3. Why we need to continue research using embryonic stem cells? 4. Time taken for discoveries 5. Examples of stem of Embryonic cell lines 8. Fertility Research using human embryos and blastocysts 1. What are stem cells? Stem

Rambaut, Andrew

177

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

Microsoft Academic Search

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

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

2002-01-01

178

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

179

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

PubMed

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

Cong, Shan; Cao, Guifang; Liu, Dongjun

2014-12-01

180

Echinomycin protects mice against relapsed acute myeloid leukemia without adverse effect on hematopoietic stem cells  

PubMed Central

Acute myeloid leukemia (AML) often relapses following chemotherapy-induced remission and is generally chemo-resistant. Given the potential role for cancer stem cells in relapse, targeting of the leukemia-initiating cell (LIC) in AML may provide improved outcome following remission induction. However, due to overlap in their self-renewal program with normal hematopoietic stem cells (HSCs), therapeutic targeting of the LIC may have an adverse effect on long-term hematopoietic recovery. Here we used a mouse model of relapsed AML to explore whether the hypoxia-inducible factor (HIF)1? inhibitor echinomycin can be used to treat relapsed AML without affecting host HSCs. We show that echinomycin cured 40% to 60% of mice transplanted with relapsed AML. Bone marrow cells from the cured mice displayed normal composition of HSCs and their progenitors and were as competent as those isolated from nonleukemic mice in competitive repopulation assays. Importantly, in mice with complete remission, echinomycin appeared to completely eliminate LICs because no leukemia could be propagated in vivo following serial transplantation. Taken together, our data demonstrate that in a mouse model of relapsed AML, low-dose echinomycin selectively targets LICs and spares normal hematopoiesis. PMID:24994068

Wang, Yin; Liu, Yan; Tang, Fei; Bernot, Kelsie M.; Schore, Reuven; Marcucci, Guido

2014-01-01

181

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

PubMed Central

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

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

2012-01-01

182

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. PMID:22007273

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

2011-01-01

183

Effect of young extrinsic environment stimulated by hypoxia on the function of aged tendon stem cell.  

PubMed

Tendon stem cells (TSCs), recently identified as tendon cells, play an important role in maintaining the homeostasis of tendon tissue. Age-related decrease in the function of TSCs has been reported. Recent reports demonstrated that hypoxic condition is advantageous for efficient expansion of TSCs. Moreover, the impaired function of aged stem cells could be modulated by exposing them to a young environment. Therefore, we investigated the effects of hypoxic-conditioned culture medium (HCCM) from young TSCs on the proliferation, migration, senescence, and tenocyte phenotype of aged TSCs. TSCs were isolated, and the conditioned medium was collected. There were 4 groups: young TSCs, aged TSCs, aged TSCs + aged HCCM, and aged TSCs + young HCCM. The proliferative capacity, migration, ?-galactosidase activity, and tenogenic differentiation potential of TSCs were assessed. Our results showed that HCCM enhanced the proliferation and migration potential of aged TSCs. Moreover, the senescence-associated ?-galactosidase activity of aged TSCs was decreased by young HCCM. After being cultured in the young HCCM, the expressions of tenocyte-related genes in aged TSCs were significantly enhanced. Together, results of this study indicate that HCCM from young TSCs may represent an effective strategy to improve the impaired function of aged TSCs. PMID:24817591

Jiang, Dapeng; Jiang, Zhitao; Zhang, Yubo; Wang, Shuai; Yang, Shulong; Xu, Bo; Yang, Mowen; Li, Zhaozhu

2014-11-01

184

Stimulatory effects of polar glycopeptidolipids of Mycobacterium chelonae on murine haematopoietic stem cells and megakaryocyte progenitors.  

PubMed

The effects of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) on haematopoietic stem cells and on megakaryocyte progenitors in bone marrow (BM) and spleen were investigated in mice. We studied the in vivo spleen colony-forming ability and marrow repopulating ability of pGPL-Mc by assays of colony-forming units-spleen (CFU-S). The number of CFU-S was increased in BM when both donors and recipients were treated with pGPL-Mc. In contrast, a single treatment of donors induced enhancement of spleen CFU-S. The number of pre-CFU-S was not significantly increased by pGPL-Mc injection. Megakaryocyte (Meg) progenitors were determined in vitro with a quantitative cultural analysis of bone marrow and spleen cells in agar in the presence of spleen-conditioned medium. A statistically significant increase in BM and spleen CFU-Meg was observed two days after the last administration of pGPL-Mc. This experiment points out the ability of pGPL-Mc to induce substantial stimulation of megakaryocytopoiesis and slight proliferation of stem cells in BM, but which is more pronounced in spleen. This molecule therefore appears to be a potential adjuvant of chemo- and radiotherapy in order to palliate the cytotoxic side effects of these cancer therapeutic modalities. PMID:9226767

Vincent-Naulleau, S; Thibault, D; Neway, T; Pilet, C

1997-02-01

185

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

PubMed Central

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

Smit, Nicoline W.; Coronel, Ruben

2014-01-01

186

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

PubMed Central

Background Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i) counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC) exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI cardiac repair than each treatment separately. We have now investigated whether sildenafil at lower doses and MDSC, alone or in combination are effective to attenuate LV remodeling after MI in rats. Methods MI was induced in rats by ligature of the left anterior descending coronary artery. Treatment groups were: “Series A”: 1) untreated; 2) oral sildenafil 3?mg/kg/day from day 1; and “Series B”: intracardiac injection at day 7 of: 3) saline; 4) rat MDSC (106 cells); 5) as #4, with sildenafil as in #2. Before surgery, and at 1 and 4?weeks, the left ventricle ejection fraction (LVEF) was measured. LV sections were stained for collagen, myofibroblasts, apoptosis, cardiomyocytes, and iNOS, followed by quantitative image analysis. Western blots estimated angiogenesis and myofibroblast accumulation, as well as potential sildenafil tachyphylaxis by PDE 5 expression. Zymography estimated MMPs 2 and 9 in serum. Results As compared to untreated MI rats, sildenafil improved LVEF, reduced collagen, myofibroblasts, and circulating MMPs, and increased cardiac troponin T. MDSC replicated most of these effects and stimulated cardiac angiogenesis. Concurrent MDSC/sildenafil counteracted cardiomyocyte and endothelial cells loss, but did not improve LVEF or angiogenesis, and upregulated PDE 5. Conclusions Long-term oral sildenafil, or MDSC given separately, reduce the MI fibrotic scar and improve left ventricular function in this rat model. The failure of the treatment combination may be due to inducing overexpression of PDE5. PMID:22871104

2012-01-01

187

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

PubMed Central

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

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

2014-01-01

188

Cell Stem Cell Adult SVZ Stem Cells Lie in a Vascular  

E-print Network

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

Lin, Gang

189

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

PubMed Central

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

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

2014-01-01

190

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

191

Elucidating Cause-Effect Relationships between Extracellular Matrix Signaling and Mesenchymal Stem Cell Differentiation  

E-print Network

Mesenchymal stem cell (MSC) differentiation is known to be influenced by a range of environmental stimuli. MSC-based bone regeneration strategies would benefit from the identification of scaffold material properties which intrinsically promote...

Becerra-Bayona, Silvia M.

2013-07-25

192

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. PMID:24024180

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

193

Effect of Gsk3 inhibitor CHIR99021 on aneuploidy levels in rat embryonic stem cells.  

PubMed

Germline competent embryonic stem (ES) cells can serve as a tool to create genetically engineered rat strains used to elucidate gene function or provide disease models. In optimum culture conditions, ES cells are able to retain their pluripotent state. The type of components present and their concentration in ES cell culture media greatly influences characteristics of ES cells including the ability to maintain the cells in a pluripotent state. We routinely use 2i media containing inhibitors CHIR99021 and PD0325901 to culture rat ES cells. CHIR99021 specifically inhibits the Gsk3? pathway. We have found that the vendor source of CHIR99021 has a measurable influence on the level of aneuploidy seen over time as rat ES cells are passaged. Karyotyping of three different rat ES cell lines passaged multiple times showed increased aneuploidy when CHIR99021 from source B was used. Mass spectrometry analysis of this inhibitor showed the presence of unexpected synthetic small molecules, which might directly or indirectly cause increases in chromosome instability. Identifying these molecules could further understanding of their influence on chromosome stability and indicate how to improve synthesis of this media component to prevent deleterious effects in culture. PMID:24519175

Bock, Anagha S; Leigh, Nathan D; Bryda, Elizabeth C

2014-06-01

194

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

2012-10-23

195

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

PubMed Central

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

Adami, Raffaella; Scesa, Giuseppe; Bottai, Daniele

2014-01-01

196

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

PubMed Central

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

2014-01-01

197

Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.  

PubMed

Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb), cyclins A and D1, as well as up-regulating p27(kip1) expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4(low)/CD8(low) T subset that had decreased secretion of IFN-?, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection. PMID:21625521

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

2011-01-01

198

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

199

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

200

DEVELOPMENTAL BIOLOGY: Orienting Stem Cells  

NSDL National Science Digital Library

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

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

2003-09-12

201

IFN-?-secreting-mesenchymal stem cells exert an antitumor effect in vivo via the TRAIL pathway.  

PubMed

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

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

2014-01-01

202

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

PubMed Central

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

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

2014-01-01

203

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

204

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

205

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

206

Enhancing spontaneous stem cell healing (Review)  

PubMed Central

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

MAGUIRE, GREG; FRIEDMAN, PETER

2014-01-01

207

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

PubMed Central

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

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

2011-01-01

208

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

PubMed

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

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

2013-01-01

209

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

PubMed Central

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

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

2013-01-01

210

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

PubMed

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

Kolar, Mallappa K; Kingham, Paul J

2014-06-01

211

Modeling Stem Cell Induction Processes  

E-print Network

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 ...

Grácio, Filipe

212

Stem cells and brain cancer  

Microsoft Academic Search

One of the most devastating CNS pathologies is brain cancer. The undifferentiated character of brain tumor cells and recent reports of cancer stem cells prompt questions regarding the involvement of normal stem\\/progenitor cells in brain tumor biology, their potential contribution to the tumor itself, and whether they are the cause or the consequence of tumor initiation and progression. The cancer

Elena I. Fomchenko; Eric C. Holland

2005-01-01

213

Human Embryonic Stem Cell Registry  

NSDL National Science Digital Library

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

2001-01-01

214

Mechanotransduction: Tuning Stem Cells Fate  

PubMed Central

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

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

2011-01-01

215

Antiproliferative and apoptotic effects of a specific antiprostate stem cell single chain antibody on human prostate cancer cells.  

PubMed

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

Nejatollahi, Foroogh; Abdi, Soghra; Asgharpour, Mahdi

2013-01-01

216

Effect of basic fibroblast growth factor in mouse embryonic stem cell culture and osteogenic differentiation.  

PubMed

Embryonic stem cells are actively explored as a cell source in tissue engineering and regenerative medicine involving bone repair. Basic fibroblast growth factor (bFGF) has been a valuable growth factor to support the culture of human stem cells as well as their osteogenic differentiation, but the influence of bFGF on mouse embryonic stem (mES) cells is not known. Towards this goal, D3 cells were treated with bFGF during maintenance conditions and during spontaneous and osteogenic differentiation. In feeder-free monolayers, up to 40?ng/ml of exogenous bFGF did not support self-renewal of mES without LIF during cell expansion. During spontaneous differentiation in high-density cultures, bFGF stimulated cell proliferation under certain conditions but did not influence differentiation, as judged by stage-specific embryonic antigen-1 expression. The addition of bFGF reduced the alkaline phosphatase (ALP) activity associated with osteoblast activity during differentiation induced by osteogenic supplements, although the extent of mineralization was unaffected by bFGF. The bFGF increased the mesenchymal stem cell marker Sca-1 in an mES cell population and led to an enhanced increase in osteocalcin and runx2 expression in combination with BMP-2. These results suggest that bFGF could be utilized to expand the cell population in high-density cultures in addition to enriching the BMP-2 responsiveness of mES cells. PMID:22674886

Rose, Laura C; Fitzsimmons, Ross; Lee, Poh; Krawetz, Roman; Rancourt, Derrick E; Uluda?, Hasan

2013-05-01

217

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

218

The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair.  

PubMed

It is reported that decellularized collagen matrices derived from dermal skin and bone have been clinically used for tendon repair. However, the varying biological and physical properties of matrices originating from different tissues may influence the differentiation of tendon stem cells, which has not been systematically evaluated. In this study, the effects of collagenous matrices derived from different tissues (tendon, bone and dermis) on the cell differentiation of human tendon stem/progenitor cells (hTSPCs) were investigated, in the context of tendon repair. It was found that all three matrices supported the adhesion and proliferation of hTSPCs despite differences in topography. Interestingly, tendon-derived decellularized matrix promoted the tendinous phenotype in hTSPCs and inhibited their osteogenesis, even under osteogenic induction conditions, through modulation of the teno- and osteolineage-specific transcription factors Scleraxis and Runx2. Bone-derived decellularized matrix robustly induced osteogenic differentiation of hTSPCs, whereas dermal skin-derived collagen matrix had no apparent effect on hTSPC differentiation. Based on the specific biological function of the tendon-derived decellularized matrix, a tissue-engineered tendon comprising TSPCs and tendon-derived matrix was successfully fabricated for Achilles tendon reconstruction. Implantation of this cell-scaffold construct led to a more mature structure (histology score: 4.08 ± 0.61 vs. 8.51 ± 1.66), larger collagen fibrils (52.2 ± 1.6 nm vs. 47.5 ± 2.8 nm) and stronger mechanical properties (stiffness: 21.68 ± 7.1 Nm m(-1) vs.13.2 ± 5.9 Nm m(-1)) of repaired tendons compared to the control group. The results suggest that stem cells promote the rate of repair of Achilles tendon in the presence of a tendinous matrix. This study thus highlights the potential of decellularized matrix for future tissue engineering applications, as well as developing a practical strategy for functional tendon regeneration by utilizing TSPCs combined with tendon-derived decellularized matrix. PMID:23896565

Yin, Zi; Chen, Xiao; Zhu, Ting; Hu, Jia-jie; Song, Hai-xin; Shen, Wei-liang; Jiang, Liu-yun; Heng, Boon Chin; Ji, Jun-feng; Ouyang, Hong-Wei

2013-12-01

219

Generation of induced pluripotent stem cells from neural stem cells  

Microsoft Academic Search

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

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

2009-01-01

220

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. PMID:24101871

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

2013-01-01

221

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

E-print Network

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

Wan, C. R.

222

Extracellular, stem cells and regenerative ophthalmology.  

PubMed

Retinal degenerative diseases, including retinitis pigmentosa, age-related macular degeneration, and glaucoma, still lack effective medical treatments. The stem cell-based regenerative approach has been proposed to treat these degenerative diseases. The major challenge for regenerative ophthalmology is to produce enough desirable retinal neurons in vitro from various stem cell types. Extracellular matrix proteins are important for stem cell self-renewal and differentiation in various systems. They have also been used in combination with various growth factors to expand retinal stem cells and produce desirable retinal neuronal types. This review summarizes our current understanding of how extracellular matrix proteins regulate stem cell function and discusses their application in regenerative ophthalmology. PMID:25275901

Wang, Yifeng; Xie, Ting

2014-01-01

223

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

PubMed Central

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

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

2013-01-01

224

Cell Stem Cell, Volume 5 Supplemental Data  

E-print Network

Cell Stem Cell, Volume 5 Supplemental Data Phosphorylation Dynamics during Early Differentiation of Human Embryonic Stem Cells Dennis Van Hoof, Javier Muñoz, Stefan R. Braam, Martijn W.H. Pinkse, Rune labeling of the cells with the heavy stable isotopes. In Solution Digestion Harvested cells were washed

225

Stem Cell Basics About this document  

E-print Network

that are the focus of scientific research, and the potential use of stem cells in research and in treating disease1 Stem Cell Basics About this document This primer on stem cells is intended for anyone who wishes to learn more about the biological properties of stem cells, the important questions about stem cells

Bandettini, Peter A.

226

Adipose-derived stem cells extract has a proliferative effect on myogenic progenitors.  

PubMed

Finding an effective method to regenerate muscle is a growing issue in the orthopedic field. Platelet-rich plasma (PRP) has recently been considered for therapeutic use due to its capacity to induce proliferation of myogenic progenitor cells (MPCs). Adipose-derived stem cells (ASCs) and its extract are regarded as a promising treatment for various disorders within the orthopedic field but their therapeutic relevance in the muscle regeneration is poorly investigated. In this study, rabbit MPCs were cultured from the supraspinatus of rabbit and characterized by myogenic markers. To investigate the paracrine effect of ASCs on MPCs, coculture experiments were performed. In order to see the anabolic effect of ASC-extracts (ASC-ex) in MPCs, cell proliferation assays were performed and compared with the PRP-added condition. Coculture experiment showed ASCs had an anabolic paracrine effect on proliferation of MPCs. PRP had a positive effect on proliferation of MPCs when compared to the control (100?±?7.4% vs 195.2?±?19.2%, p?cells, PRP showed an increased rate when compared to the control (100?±?5.9% vs 205.1?±?45.4%, p?effect on expanding MPCs of rabbit and myoblast cell line, and its capacity to induce proliferation was notably stronger than that of PRP. In conclusion, the study suggests that rabbit ASC-ex have stronger proliferative effect on MPCs than rabbit PRP. Thus, ASC-ex could be a therapeutic candidate for muscle regeneration by activation of endogenous MPCs. PMID:24719183

Im, Wooseok; Ban, Jae-Jun; Lim, Jiyeon; Lee, Mijung; Chung, Jin Young; Bhattacharya, Roshmi; Kim, Sae Hoon

2014-09-01

227

TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells.  

PubMed

Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreas-derived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSC(nsTRAIL) and MSC(stTRAIL). The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types. PMID:22767216

Moniri, M R; Sun, X-Y; Rayat, J; Dai, D; Ao, Z; He, Z; Verchere, C B; Dai, L-J; Warnock, G L

2012-09-01

228

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

229

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

PubMed

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

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

2013-10-01

230

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.

231

Emodin As an Effective Agent in Targeting Cancer Stem-Like Side Population Cells of Gallbladder Carcinoma  

PubMed Central

Side population (SP) cells are previously identified from bone marrow based on their capacity to efflux of the fluorescent dye Hoechst 33342. Recent studies demonstrate that SP cells isolated from various cancer cell lines and primary tumors possess stem-cell-like properties. Thus, targeting tumor SP cells may provide new strategies for treatment in clinic. We previously showed that 1,3,8-trihydroxy-6-methylanthraquinone (emodin), a reactive oxygen species (ROS) generator, enhanced sensitivity of gallbladder cancer SGC-996 cells to cisplatin (CDDP) via generation of ROS and downregulation of multidrug-resistance-associated protein 1 (MRP1). To determine whether emodin also acts effectively on cancer stem cells of gallbladder carcinoma, we use SP cells as a model of cancer stem-cell-like cells. Here, we found that emodin, via ROS-related mechanism and suppressing the function of ATP-binding cassette super-family G member (ABCG2), which is known to be associated with Hoechst dye efflux activity of SP cells, not only reduced the ratio, inhibited clone formation, and eliminated sphere formation of SP cells effectively, but also promoted obviously the intracellular accumulation of doxorubicin, the main substrate of the efflux pump ABCG2. In addition, emodin could sensitize CDDP, via inhibition of expression of ABCG2, to overcome chemoresistance of SP cells. Importantly, similar to the experiment in vitro, emodin/CDDP co-treatment in vivo suppressed the tumor growth derived from SP cells through downregulating ABCG2 expression. Our results suggest that emodin is an effective agent targeting cancer stem-like SP cells of gallbladder carcinoma, either alone or acts as a chemotherapy enhancer. PMID:22974371

Li, Xin-xing; Dong, Ying; Wang, Wei; Wang, Hao-lu; Chen, Yu-ying; Shi, Gui-ying; Yi, Jing

2013-01-01

232

Regulating the leukemia stem cell  

PubMed Central

Leukemia stem cells (LSCs) are responsible for sustaining and propagating malignant disease, and, as such, are promising targets for therapy. Studies of human LSCs have served an important role in defining the major tenets of the cancer stem cell model, which center on the frequencies of cancer stem cells, their potential hierarchical organization, and their degree of maturation. LSCs in acute myeloid leukemia (AML) have recently been studied using mouse syngeneic models of leukemia induced by MLL oncogenes. These studies have revealed that LSCs are more analogous to progenitor cells and employ embryonic stem cell-like genetic programs for their maintenance, prompting a refinement of the original cancer stem cell model with important implications for design of therapies to selectively target LSCs. PMID:19959097

Cleary, Michael L.

2009-01-01

233

Bioprinting for stem cell research  

PubMed Central

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

Tasoglu, Savas; Demirci, Utkan

2012-01-01

234

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. PMID:23812084

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

2013-01-01

235

Stem cell tracking using iron oxide nanoparticles  

PubMed Central

Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored. PMID:24729700

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

2014-01-01

236

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

PubMed

Lactoferrin (LF) is a bioactive glycoprotein that became recently interesting in the field of bone regeneration for its modulatory effect on bone cells. On the basis of this evidence this work aims to functionalize biomimetic hydroxyapatite (HA) nanocrystals with LF to study their effect on osteogenic differentiation of mesenchymal stem cells (MSCs). The orientation of LF on the HA surface was analyzed by spectroscopic and thermal techniques. Three samples with different amounts of LF attached to HA nanocrystals were tested in vitro. The combined effect of HA and LF on MSC proliferation and morphology, alkaline phosphatase (ALP) activity, and gene expression were evaluated at different time points. The sample with the lowest LF amount showed the best bioactivity probably due to the formation of a single layer of protein with a better molecular orientation. Coupling of HA-LF did not affect cell proliferation and morphology, while analysis of HA-LF on ALP activity and messenger RNA expression of the selected genes, demonstrated the role of HA-LF in the induction of osteogenic markers. HA-LF represents a promising system to be used to manufacture bioactive functional materials in tissue engineering (as scaffolds, injectable cements, or coatings for metallic implants) with enhanced anabolic activity to treat bone diseases. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 224-234, 2015. PMID:24639083

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

2015-01-01

237

International stem cell research considerations  

Microsoft Academic Search

Legislative bodies in the international arena and in individual countries are actively engaged in developing policies regarding the establishment, distribution and use of human embryonic stem cells. Present and anticipated policies concerning research on human adult and embryonic stem cells of possible medical importance reflect the wide spectrum of popular views that range from complete rejection to enthusiastic support. Since

Heiner Westphal

2002-01-01

238

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

Microsoft Academic Search

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

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

2011-01-01

239

Cell Stem Cell Sic Transit Gloria  

E-print Network

, Cambridge CB2 0RE, UK 4Wellcome Trust Centre for Stem Cell Research, Tennis Court Road, Cambridge CB2 1QRCell Stem Cell Review Sic Transit Gloria: Farewell to the Epidermal Transit Amplifying Cell? Philip H. Jones,1,* Benjamin D. Simons,2 and Fiona M. Watt3,4 1MRC Cancer Cell Unit, Hutchison-MRC Research

Simons, Ben

240

Cell Stem Cell Induction of Multipotential Hematopoietic  

E-print Network

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

Collins, James J.

241

[Plasticity of tissue stem cells].  

PubMed

In the early stages of embryonic development, cells have the capability of dividing indefinitely and then differentiating into any type of cell in the body. Recent studies have revealed that much of this remarkable developmental potential of stem cells is retained by small populations of cells within most tissues in the adult. Intercellular signals that control the proliferation, differentiation and survival of tissue stem cells in their niches are being identified and include a diverse array of morphogens, cytokines, chemokines and cell adhesion molecules. Adult tissue stem cells, moreover, can also differentiate into developmentally unrelated cell types, such as nerve stem cells into blood cells. Currently, we can only speculate about the mechanisms involved in such dramatic changes in cell fate. For example, the emergence of, say, hematopoietic stem cells from brain neurospheres could involve either transdifferentiation (brain-->blood) or dedifferentiation (brain-->pluripotent cells), or by the actions of rare, but residual pluripotent stem cells. This issue is central to understanding the molecular basis of commitment and lies at the heart of debates about plasticity and the reversibility of developmental restriction. PMID:12053651

Uher, Ferenc; Vas, Virág

2002-05-01

242

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. PMID:22312315

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

243

FDA Warns About Stem Cell Claims  

MedlinePLUS

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

244

What's It Like to Donate Stem Cells?  

MedlinePLUS

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

245

Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation.  

PubMed

The primary and secondary immune responses to thymus-dependent and -independent antigens were evaluated in normal male and female mice and in castrated male mice. Both IgM antibody production in the primary response and IgG antibody production in the secondary response were enhanced in females vs. males of equivalent age. Castration of the male converted this animal to a female in terms of responsiveness to the thymus-dependent group of antigens, while inducing equivalent or even greater enhanced responsiveness over the female to the thymus-independent antigen, polyvinylpyrrolidone. Further characteristics of the changes in lymphoid organs were determined in the castrated animal vs. normal males and females. It was shown that the spleen and thymus became markedly hyperplastic, the organ weights exceeding the female, which in turn were greater than in the male. The enhanced weight of the thymus was shown to be due to increased numbers of cortisone-sensitive cells, the absolute number of cortisone-resistant cells remaining equivalent to normal males and females. Thus, the increased thymic weight of the female also resided in the cortisone-sensitive population. Peripheral lymphocyte counts in castrated animals exceeded both normal males and females. Further experiments in gonadectomized males provided evidence that increased thymic cell activity per se played a role in enhanced response to thymus-dependent antigens, but that a thymic-derived hormone mediated the enhanced effect to the thymus-independent antigen in the castrated animal. The capacity for loss of androgenic hormone-producing tissue to generate enhanced differentiation of stem cells was denoted by experiments in which numbers of spleen colonies and uptake of (59)Fe, employed as an index of hematopoiesis 1 wk after reconstitution of lethally irradiated castrated and normal recipients, were enhanced in gonadectomized male animals. Thus, in summary, changes in sex hormone levels exerted a marked influence on immune responsiveness and stem cell differentiation, by increasing numbers of functioning cells, by promoting cellular differentiation, as well as by promoting cellular function via hormonal effects. PMID:4538840

Eidinger, D; Garrett, T J

1972-11-01

246

Allogenicity & immunogenicity in regenerative stem cell therapy  

PubMed Central

The development of regenerative medicine relies in part on the capacity of stem cells to differentiate into specialized cell types and reconstitute tissues and organs. The origin of the stem cells matters. While autologous cells were initially the preferred ones the need for “off the shelf” cells is becoming prevalent. These cells will be immediately available and they originate from young non diseased individuals. However their allogenicity can be viewed as a limitation to their use. Recent works including our own show that allogenicity of stem cell can be viewed as on one hand detrimental leading to their elimination and on the other hand beneficial through a paracrine effect that can induce a local tissue regenerative effect from endogenous stem cells. Also their immune modulatory capacity can be harnessed to favor regeneration. Therefore the immune phenotype of stem cells is an important criteria to be considered before their clinical use. Immuno monitoring of the consequences of their in vivo injection needs to be taken into account. Transplantation immunology knowledge will be instrumental to enable the development of safe personalized regenerative stem cell therapy. PMID:24434327

Charron, Dominique

2013-01-01

247

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

PubMed

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

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

2014-01-30

248

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

PubMed Central

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

2013-01-01

249

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

PubMed Central

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

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

2013-01-01

250

Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer's disease model.  

PubMed

Amyloid beta (A?) plays a major role in Alzheimer's disease (AD), and neuroinflammatory processes mediated by A? plaque-induced microglial cells and astrocytes contribute to AD pathogenesis. The present study examined human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs), which have potent immunomodulatory and paracrine effects in a Tg2576 (APPswe) transgenic mouse model of AD. AMSCs secreted high levels of transforming growth factor-? under in vitro inflammatory environment conditions. Six weeks after the intravenous injection of AMSCs, APPswe mice showed evidence of improved spatial learning, which significantly correlated with the observation of fewer A? plaques in brain. The number of ED1-positive phagocytic microglial cells associated with A? plaques was higher in AMSC-injected mice than in phosphate-buffered saline-injected mice, and the level of A?-degrading enzymes (matrix metallopeptidase-9 and insulin-degrading enzyme) was also significantly higher. Furthermore, the level of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-?, was lower and that of anti-inflammatory cytokines, interleukin-10 and transforming growth factor-?, was higher in AMSC-injected mice than phosphate-buffered saline-injected mice. These effects lasted until 12 weeks after AMSC injection. Taken together, these results collectively suggest that injection of AMSCs might show significant long-lasting improvement in AD pathology and memory function via immunomodulatory and paracrine mechanisms. PMID:23623603

Kim, Kyung-Sul; Kim, Hyun Sook; Park, Ji-Min; Kim, Han Wool; Park, Mi-Kyung; Lee, Hyun-Seob; Lim, Dae Seog; Lee, Tae Hee; Chopp, Michael; Moon, Jisook

2013-10-01

251

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. 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

2013-01-01

252

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

253

Targeting Leukemia Stem Cells and Stem Cell Pathways in ALL  

Microsoft Academic Search

\\u000a Growing evidence suggests that haematological malignancies are ­sustained by a critical population of leukemia-initiating\\u000a cells or leukemia stem cells. These cellular populations are likely to be the critical target for eradication of leukemia\\u000a and most likely form the reservoir for relapse and disease resistance. Leukemia stem cells (LSC) have been demonstrated in\\u000a Acute Lymphoblastic Leukemia (ALL), although their origins, identity

Clare Pridans; Brian J. P. Huntly

254

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

255

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

PubMed Central

In the adult hippocampus, neurogenesis—the process of generating mature granule cells from adult neural stem cells—occurs throughout the entire lifetime. In order to investigate the involved regulatory mechanisms, knockout (KO) experiments, which modify the dynamic behaviour of this process, were conducted in the past. Evaluating these KOs is a non-trivial task owing to the complicated nature of the hippocampal neurogenic niche. In this study, we model neurogenesis as a multicompartmental system of ordinary differential equations based on experimental data. To analyse the results of KO experiments, we investigate how changes of cell properties, reflected by model parameters, influence the dynamics of cell counts and of the experimentally observed counts of cells labelled by the cell division marker bromodeoxyuridine (BrdU). We find that changing cell proliferation rates or the fraction of self-renewal, reflecting the balance between symmetric and asymmetric cell divisions, may result in multiple time phases in the response of the system, such as an initial increase in cell counts followed by a decrease. Furthermore, these phases may be qualitatively different in cells at different differentiation stages and even between mitotically labelled cells and all cells existing in the system. PMID:24598209

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

2014-01-01

256

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

2013-01-01

257

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

PubMed Central

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

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

2014-01-01

258

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

PubMed

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

Chang, Jing; Tang, Li; Lei, Han; Zhang, Xiao-Gang; Zuo, Zhong; Huang, Wei; Fu, Hang

2014-11-01

259

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

PubMed Central

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

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

2014-01-01

260

Effect of substrate stiffness on early human embryonic stem cell differentiation  

PubMed Central

Background The pluripotency and self renewing properties of human embryonic stem cells (hESC) make them a valuable tool in the fields of developmental biology, pharmacology and regenerative medicine. Therefore, there exists immense interest in devising strategies for hESC propagation and differentiation. Methods involving simulation of the native stem cell microenvironment, both chemical and physical, have received a lot of attention in recent years. Equally important is evidence that cells can also sense the mechanical properties of their microenvironment. In this study, we test the hypothesis that hESCs accept mechanical cues for differentiation from the substrate by culturing them on flexible polydimethylsiloxane (PDMS) of varying stiffness. Results PDMS substrates were prepared using available commercial formulations and characterized for stiffness, surface properties and efficiency of cell attachment and proliferation. Across different substrate stiffness, cell numbers, cell attachment and cell surface area were found to be similar. Expression of pluripotency markers decreased with increased time in culture across all PDMS substrates of varying stiffness. Analysis of gene expression of differentiation markers indicates that the differentiation process becomes less stochastic with longer culture times. Conclusions We evaluated the utility of PDMS substrates for stem cell propagation and substrate mediated differentiation. The stiffness affected gene expression of pluripotent and differentiation markers with results indicating that these substrate systems could potentially be used to direct hESC fate towards early mesodermal lineages. This study suggests that coupled with soluble factors, PDMS substrates could potentially be useful in generating defined populations of differentiated cells. PMID:23517522

2013-01-01

261

The effects of 1,25-dihydroxyvitamin D3 on in vitro human NK cell development from hematopoietic stem cells.  

PubMed

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is the biologically active form of vitamin D and is immunoregulatory. 1,25(OH)2D3 binds the vitamin D receptor complex present in many immune populations and can illicit transcriptional responses that vary among different immune subsets. The effects of 1,25(OH)2D3 on mature and developing human NK cells are not well characterized. In the present study, we examined the influence of 1,25(OH)2D3 using an established NK cell differentiation system. Briefly, umbilical cord blood CD34(+) cells were isolated and cultured in conditions optimal for NK cell differentiation, and varying concentrations of 1,25(OH)2D3 were administered. At physiological concentrations (10 nM), 1,25(OH)2D3 impaired NK cell development. Moreover, the NK cells that did develop under the influence of 1,25(OH)2D3 showed a significant reduction in function (cytotoxicity and cytokine production). Conversely, 1,25(OH)2D3 strongly induced hematopoietic stem cells to differentiate along a myeloid pathway, giving rise to CD14(+) cells. Mechanistically, 1,25(OH)2D3 drives hematopoietic progenitor cells to rapidly upregulate monocyte genes (i.e., C/EBP-? and CD14). There were no effects of 1,25(OH)2D3 on mature NK cytotoxicity or cytokine production. Collectively, these studies provide novel data showing the negative regulatory effect of 1,25(OH)2D3 on NK cell development. PMID:25149465

Weeres, Matthew A; Robien, Kim; Ahn, Yong-Oon; Neulen, Marie-Luise; Bergerson, Rachel; Miller, Jeffery S; Verneris, Michael R

2014-10-01

262

GPCRs in Stem Cell Function  

PubMed Central

Many tissues of the body cannot only repair themselves, but also self-renew, a property mainly due to stem cells and the various mechanisms that regulate their behavior. Stem cell biology is a relatively new field. While advances are slowly being realized, stem cells possess huge potential to ameliorate disease and counteract the aging process, causing its speculation as the next panacea. Amidst public pressure to advance rapidly to clinical trials, there is a need to understand the biology of stem cells and to support basic research programs. Without a proper comprehension of how cells and tissues are maintained during the adult life span, clinical trials are bound to fail. This review will cover the basic biology of stem cells, the various types of stem cells, their potential function, and the advantages and disadvantages to their use in medicine. We will next cover the role of G-protein coupled receptors in the regulation of stem cells and their potential in future clinical applications. PMID:23415095

DOZE, VAN A.; PEREZ, DIANNE M.

2013-01-01

263

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

PubMed

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

Rauner, Gat; Barash, Itamar

2014-10-15

264

Stem cell therapy for autism.  

PubMed

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

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

2007-01-01

265

Stem Cell Therapy for Autism  

PubMed Central

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

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

2007-01-01

266

Effect of prior rituximab on high-dose therapy and autologous stem cell transplantation in follicular lymphoma  

Microsoft Academic Search

Autologous stem-cell transplantation (ASCT) has been used in follicular lymphoma (FL) to achieve durable responses in first remission or in the relapsed or refractory settings. Addition of rituximab to chemotherapy for FL has been shown to improve survival. The impact of prior therapy with rituximab upon the effectiveness of high-dose therapy (HDT) and ASCT in patients with FL is unknown.

T Y Kang; L A Rybicki; B J Bolwell; S G Thakkar; S Brown; R Dean; M A Sekeres; A Advani; R Sobecks; M Kalaycio; B Pohlman; J W Sweetenham

2007-01-01

267

Alginate encapsulation and hepatic differentiation of embryonic stem cells  

Microsoft Academic Search

The emergence of cell based clinical technologies has been limited by the need for large cell masses (>1011 cells). Embryonic stem cells are a promising solution to this cell source limitation because they are highly proliferative, renewable and pluripotent. Although many investigators have described techniques to effectively differentiate stem cells into a variety of mature cell lineages, these fall short

T. J. Maguire; E. I. Novik; R. Schloss; M. L. Yarmush

2005-01-01

268

Adult Stem Cells and Diseases of Aging  

PubMed Central

Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

Boyette, Lisa B.; Tuan, Rocky S.

2014-01-01

269

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

SciTech Connect

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

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

1995-03-30

270

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

271

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

PubMed Central

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

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

2011-01-01

272

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

PubMed Central

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

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

2013-01-01

273

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

SciTech Connect

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

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

2010-09-10

274

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

PubMed

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

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

2014-03-10

275

Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells.  

PubMed

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, CD34 and CD45. When plated on adipogenic, chondrogenic and osteogenic media, fMSC differentiated into the respective cell lineage. Compared to adult MSC (aMSC), the proliferative capacity of fMSC was higher. Mitogen stimulation of PBL was inhibited by fMSC. The greatest inhibition (78%) was seen when 30,000 fMSCs were added to 150,000 lymphocytes stimulated by phytohaemagglutinin. Adult and fMSCs were added to mixed lymphocyte cultures (MLC) containing peripheral blood lymphocytes or foetal liver cells. Unlike aMSC, fMSCs did not inhibit MLC. fMSC could be culture-expanded several million folds with no loss of phenotype characteristics, which makes them ideal for ex vivo expansion. fMSC inhibit lymphocyte proliferation induced by mitogens, but not alloreactivity as measured by MLC. PMID:12858197

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

2003-08-01

276

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. PMID:23671817

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

2013-01-01

277

Extracellular matrix modulates the biological effects of melatonin in mesenchymal stem cells.  

PubMed

Both self-renewal and lineage-specific differentiation of mesenchymal stem cells (MSCs) are triggered by their in vivo microenvironment including the extracellular matrix (ECM) and secreted hormones. The ECM may modulate the physiological functions of hormones by providing binding sites and by regulating downstream signaling pathways. Thus, the purpose of this study was to evaluate the degree of adsorption of melatonin to a natural cell-deposited ECM and the effects of this interaction on the biological functions of melatonin in human bone marrow-derived MSCs (BM-MSCs). The fibrillar microstructure, matrix composition, and melatonin-binding affinity of decellularized ECM were characterized. The cell-deposited ECM improved melatonin-mediated cell proliferation by 31.4%, attenuated accumulation of intracellular reactive oxygen species accumulation, and increased superoxide dismutase (SOD) mRNA and protein expression. Interaction with ECM significantly enhanced the osteogenic effects of melatonin on BM-MSCs by increasing calcium deposition by 30.5%, up-regulating osteoblast-specific gene expression and down-regulating matrix metalloproteinase (MMP) expression. The underlying mechanisms of these changes in expression may involve intracellular antioxidant enzymes, because osteoblast-specific genes were down-regulated, whereas MMP expression was up-regulated, in the presence of SOD-specific inhibitors. Collectively, our findings indicate the importance of native ECM in modulating the osteoinductive and antioxidant effects of melatonin and provide a novel platform for studying the biological actions of growth factors or hormones in a physiologically relevant microenvironment. Moreover, a better understanding of the enhancement of MSC growth and osteogenic differentiation resulting from the combination of ECM and melatonin could improve the design of graft substitutes for skeletal tissue engineering. PMID:25210047

He, Fan; Liu, Xiaozhen; Xiong, Ke; Chen, Sijin; Zhou, Long; Cui, Wenguo; Pan, Guoqing; Luo, Zong-Ping; Pei, Ming; Gong, Yihong

2014-11-01

278

Neuroprotective effect of neural stem cell-conditioned media in in vitro model of Huntington's disease.  

PubMed

Although neural stem cell (NSC) transplantation has been investigated as a promising tool for reconstituting damaged brains, recent evidences suggest that NSCs may rescue the brain via paracrine effects rather than by direct cell replacements. In this study, we attempted to determine the neuroprotective effect of NSC-conditioned media (NSC-CM) in in vitro model of Huntington's disease. Cerebral hybrid neurons (A1) were transfected with either wild-type huntingtin (18 CAG repeats) or mutant huntingtin (100 CAG repeats). At 24h after the transfection, immunocytochemical patterns of the huntingtin aggregations, as well as the level of N-terminal proteolytic cleavages of huntingtin were analyzed. Neuronal apoptosis was evaluated with flowcytometry after Annexin-V and propidium iodide (PI) staining. Cerebral hybrid neurons transfected with mutant huntingtin showed five aggregates patterns, including diffuse cytoplasmic, dispered vacuoles, perinuclear vacuoles, nuclear inclusions (NI), and cytoplasmic inclusions (CI). NSC-CM reduced the levels of nuclear and cytoplasmic inclusions. The transfection with mutant huntingtin increased the level of N-terminal cleavages, which was reduced by the NSC-CM treatment. In addition, NSC-CM reduced the Annexin-V(+)PI(+) and Annexin-V(+)PI(-) neurons which were induced by the mutant huntingtin transfection. In summary, NSC-CM was neuroprotective in in vitro model of Huntington's disease with modulating mutant huntingtin-induced cytotoxicity. PMID:18343580

Lim, Heon-Chang; Lee, Soon-Tae; Chu, Kon; Joo, Kyung Min; Kang, Lami; Im, Woo-Seok; Park, Joung-Eun; Kim, Seung U; Kim, Manho; Cha, Choong-Ik

2008-04-25

279

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

280

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

281

Stem cell therapy for the spinal cord.  

PubMed

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

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

2012-01-01

282

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. PMID:22776143

2012-01-01

283

Stem cells, retinal ganglion cells and glaucoma.  

PubMed

Retinal ganglion cells (RGCs) represent an essential neuronal cell type for vision. These cells receive inputs from light-sensing photoreceptors via retinal interneurons and then relay these signals to the brain for further processing. RGC diseases that result in cell death, e.g. glaucoma, often lead to permanent damage since mammalian nerves do not regenerate. Stem cell differentiation can generate cells needed for replacement or can be used to generate cells capable of secreting protective factors to promote survival. In addition, stem cell-derived cells can be used in drug screening research. Here, we discuss the current state of stem cell research potential for interference in glaucoma and other optic nerve diseases with a focus on stem cell differentiation to RGCs. PMID:24732765

Sluch, Valentin M; Zack, Donald J

2014-01-01

284

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

285

UCLA stem cell scientists discover new airway stem cell:  

Cancer.gov

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

286

Issues in-depth: Setting FIRES to stem cell research  

NSDL National Science Digital Library

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

Miller, Roxanne G.

2005-07-01

287

Asymmetric stem cell division: precision for robustness.  

PubMed

Asymmetric cell division (ACD) produces two daughter cells with distinct fates or characteristics. Many adult stem cells use ACD as a means of maintaining stem cell number and thus tissue homeostasis. Here, we review recent progress on ACD, discussing conservation between stem and non-stem cell systems, molecular mechanisms, and the biological meaning of ACD. PMID:23040475

Inaba, Mayu; Yamashita, Yukiko M

2012-10-01

288

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

289

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

290

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. 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

2013-01-01

291

Alginate Composition Effects on a Neural Stem Cell-Seeded Scaffold  

PubMed Central

The purpose of this study was to evaluate the effects of alginate composition on the neurotrophic factor release, viability, and proliferation of encapsulated neural stem cells (NSCs), as well as on the mechanical stability of the scaffold itself. Four compositions were tested: a high guluronic acid (68%) and a high mannuronic acid (54%) content alginate, with or without a poly-L-lysine (PLL) coating layer. Enzyme-linked immunosorbent assay was used to quantify the release of brain-derived neurotrophic factor, glial-derived neurotrophic factor, and nerve growth factor from the encapsulated cells. All three factors were detected from encapsulated cells only when a high L-guluronic acid alginate without PLL was used. Additionally, capsules with this composition remained intact more frequently when exposed to solutions of low osmolarity, potentially indicating superior mechanical stability. Alginate beads with a PLL-coated, high D-mannuronic acid composition were the most prone to breakage in the osmotic pressure test, and were too fragile for histology and proliferation assays after 1 week in vitro. NSCs survived and proliferated in the three remaining alginate compositions similarly over the 21-day study course irrespective of scaffold condition. NSC-seeded alginate beads with a high L-guluronic acid, non-PLL-coated composition may be useful in the repair of injured nervous tissue, where the mechanism is the secretion of neuroprotective factors. We verify the neuroprotective effects of medium conditioned by NSC-seeded alginate beads on the serum withdrawal–mediated death of PC-12 cells here. PMID:19368511

Purcell, Erin K.; Singh, Aparna

2009-01-01

292

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

PubMed Central

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

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

2012-01-01

293

Engineering tissue from human embryonic stem cells  

PubMed Central

Recent advances in human embryonic stem cell (hESC) biology now offer an alternative cell source for tissue engineers, as these cells are capable of proliferating indefinitely and differentiating to many clinically relevant cell types. Novel culture methods capable of exerting spatial and temporal control over the stem cell microenvironment allow for more efficient expansion of hESCs, and significant advances have been made toward improving our understanding of the biophysical and biochemical cues that direct stem cell fate choices. Effective production of lineage specific progenitors or terminally differentiated cells enables researchers to incorporate hESC derivatives into engineered tissue constructs. Here we describe current efforts using hESCs as a cell source for tissue engineering applications, highlighting potential advantages of hESCs over current practices as well as challenges which must be overcome. PMID:18194458

Metallo, Christian M.; Azarin, Samira M.; Ji, Lin; de Pablo, Juan J.; Palecek, Sean P.

2009-01-01

294

Sources of Stem Cells for Transplant  

MedlinePLUS

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

295

Stem Cell Transplant Patients and Fungal Infections  

MedlinePLUS

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

296

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

PubMed Central

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

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

2014-01-01

297

Dental stem cells--characteristics and potential.  

PubMed

Soft dental tissues have been identified as easily accessible sources of multipotent postnatal stem cells. Dental stem cells are mesenchymal stem cells (MSC) capable of differentiating into at least three distinct cell lineages: osteo/odontogenic, adipogenic and neurogenic. They express various markers including those specific for MSC, embryonic stem cells and neural cells. Five different types of dental stem cells have been isolated from mature and immature teeth: dental pulp stem cells, stem cells from exfoliated deciduous teeth, periodontal ligament stem cells, stem cells from apical papilla and dental follicle progenitor cells. Dental stem cells may be used in dental tissue engineering including dental, enamel and periodontal tissue regeneration. They could also be used as a promising tool in potential treatment of neurodegenerative, ischemic and immune diseases. PMID:24446280

Bojic, Sanja; Volarevic, Vladislav; Ljujic, Biljana; Stojkovic, Miodrag

2014-06-01

298

Therapeutic effect of neural stem cells expressing TRAIL and bortezomib in mice with glioma xenografts  

Microsoft Academic Search

Treatment of glioblastoma remains a challenge in neuro-oncology. We investigated if treatment with neural stem cells engineered to express membrane-bound TRAIL (NSCs-mTRAIL) alone or in combination with proteasome inhibitors is a feasible therapeutic approach for experimental glioma. Glioma cells showed resistance to soluble TRAIL and proteasome inhibitors alone, but responded well to their combined treatment. In co-culture with NSCs-mTRAIL, glioma

Irina V. Balyasnikova; Sherise D. Ferguson; Yu Han; Feifei Liu; Maciej S. Lesniak

2011-01-01

299

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

Microsoft Academic Search

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

Carla F. Kim

2007-01-01

300

Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming hypothesis of cancer?  

PubMed

This article as designed to examine whether the "stoichiometric" or "elite models" of the origin of the "induced pluripotent stem" (iPS) cells fits some experiment facts from the developmental biology of adult stem cells and from the field of cancer research. In brief, since the evidence presented to support the stoichiometric model failed to recognize the factual existence of adult organ specific stem cells, the model has not been rigorously tested. In addition, the demonstration of a subset of cells (MUSE cells) in normal primary in vitro cultures of human fibroblasts (the usual source of iPS cells) seems to be the origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem cell" versus "de-differentiation" or "reprogramming" hypotheses were examined. Again, using the role of glycolysis, known to be associated with the Warburg effect in cancer cells, a list of experiments showing that (a) normal stem cells, which have few mitochondria, metabolize via glycolysis; (b) the stem cells are targets for "initiation" or "immortalization" or the blockage of differentiation and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate dehydrogenase A (LDHA), when expressed, is associated with glycolysis and therefore, must be expressed in normal adult stem cells, as well as in cancer cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen, is associated with the reduction of mitochondrial function and mass and is associated with the Warburg effect. Together, these observations from the iPS and "cancer stem cell" fields support the idea that both iPS cells and cancer stem cell are derived from adult organ-specific stem cells that do not restore or switch their metabolism of glucose from oxidative metabolism to glycolysis but, rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is prevented from differentiation or from metabolizing by oxidative phosphorylation. PMID:24293264

Trosko, James E

2014-01-01

301

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

PubMed

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

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

2014-03-01

302

Bone morphogenetic protein-9 effectively induces osteo/odontoblastic differentiation of the reversibly immortalized stem cells of dental apical papilla.  

PubMed

Dental pulp/dentin regeneration using dental stem cells combined with odontogenic factors may offer great promise to treat and/or prevent premature tooth loss. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing bone formation. Here, we investigate whether BMP9 can effectively induce odontogenic differentiation of the stem cells from mouse apical papilla (SCAPs). Using a reversible immortalization system expressing SV40 T flanked with Cre/loxP sites, we demonstrate that the SCAPs can be immortalized, resulting in immortalized SCAPs (iSCAPs) that express mesenchymal stem cell markers. BMP9 upregulates Runx2, Sox9, and PPAR?2 and odontoblastic markers, and induces alkaline phosphatase activity and matrix mineralization in the iSCAPs. Cre-mediated removal of SV40 T antigen decreases iSCAP proliferation. The in vivo stem cell implantation studies indicate that iSCAPs can differentiate into bone, cartilage, and, to lesser extent, adipocytes upon BMP9 stimulation. Our results demonstrate that the conditionally iSCAPs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages, including osteo/odontoblastic differentiation. Thus, the reversibly iSCAPs may serve as an important tool to study SCAP biology and SCAP translational use in tooth engineering. Further, BMP9 may be explored as a novel and efficacious factor for odontogenic regeneration. PMID:24517722

Wang, Jinhua; Zhang, Hongmei; Zhang, Wenwen; Huang, Enyi; Wang, Ning; Wu, Ningning; Wen, Sheng; Chen, Xian; Liao, Zhan; Deng, Fang; Yin, Liangjun; Zhang, Junhui; Zhang, Qian; Yan, Zhengjian; Liu, Wei; Zhang, Zhonglin; Ye, Jixing; Deng, Youlin; Luu, Hue H; Haydon, Rex C; He, Tong-Chuan; Deng, Feng

2014-06-15

303

Chemicals that modulate stem cell differentiation  

PubMed Central

Important cellular processes such as cell fate are likely to be controlled by an elaborate orchestration of multiple signaling pathways, many of which are still not well understood or known. Because protein kinases, the members of a large family of proteins involved in modulating many known signaling pathways, are likely to play important roles in balancing multiple signals to modulate cell fate, we focused our initial search for chemical reagents that regulate stem cell fate among known inhibitors of protein kinases. We have screened 41 characterized inhibitors of six major protein kinase subfamilies to alter the orchestration of multiple signaling pathways involved in differentiation of stem cells. We found that some of them cause recognizable changes in the differentiation rates of two types of stem cells, rat mesenchymal stem cells (MSCs) and mouse embryonic stem cells (ESCs). Among many, we describe the two most effective derivatives of the same scaffold compound, isoquinolinesulfonamide, on the stem cell differentiation: rat MSCs to chondrocytes and mouse ESCs to dopaminergic neurons. PMID:18480249

Hwang, Ki-Chul; Kim, Ji Young; Chang, Woochul; Kim, Dae-Sung; Lim, Soyeon; Kang, Sang-Moon; Song, Byeong-Wook; Ha, Hye-Yeong; Huh, Yong Joon; Choi, In-Geol; Hwang, Dong-Youn; Song, Heesang; Jang, Yangsoo; Chung, Namsik; Kim, Sung-Hou; Kim, Dong-Wook

2008-01-01

304

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. PMID:22654885

Hirayama, Masahiro; Azuma, Eiichi; Komada, Yoshihiro

2012-01-01

305

Effect of parathyroid hormone on early chondrogenic differentiation from mesenchymal stem cells  

PubMed Central

Background Treatment of articular cartilage injuries remains a difficult challenge due to the limited capacity for intrinsic repair. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes under certain culture conditions. This study focused on the modulatory effects of parathyroid hormone (PTH) on chondrogenic differentiation from MSCs. Methods MSCs were treated with various concentrations of PTH under chondrogenic pellet culture condition. RNA was isolated for real-time polymerase chain reaction (PCR) and gene expressions of collagen type II ?1 chain (Col2a1), collagen type X ?1 chain, collagen type I ?1 chain, SRY-box9 (Sox9), and type 1 PTH/PTHrP receptor (PTH1R) were examined. Chondrogenic differentiation was also evaluated by histological findings. Results PTH had opposite effects on chondrogenesis, depending on the concentration. A low to moderate concentration of PTH promoted chondrogenic differentiation of MSCs with increased expression of Sox9, Col2a1, and PTH1R, whereas chondrogenesis of MSCs was inhibited rather than stimulated with a higher concentration of PTH. Conclusion This study provides insights into the modulatory effect of PTH on chondrogenic differentiation from MSCs and the therapeutic potential for cartilage regeneration. Based on clinical experience regarding the efficacy and safety of PTH for bone metabolism, PTH may also be useful clinically for cartilage repair. PMID:25079095

2014-01-01

306

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

307

Cell Stem Cell Stage-Specific Differences in the  

E-print Network

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

Hay, Bruce A.

308

Framework bolsters stem cell progress.  

PubMed

With many of the leading science nations still stuck in debates on the use of embryonic stem cells, Britain, with a regulatory framework in place, is well-positioned to take the lead. Michael Gross reports. PMID:15296763

Gross, Michael

2004-08-10

309

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

310

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

PubMed Central

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

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

2014-01-01

311

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

312

Direct cell contact influences bone marrow mesenchymal stem cell fate.  

PubMed

Adult bone marrow-derived mesenchymal stem cells (MSC) can differentiate into various cell types of mesenchymal origin, but mechanisms regulating such cellular changes are unclear. We have conducted co-culture experiments to examine whether mesenchymal stem cell differentiation is influenced by indirect or direct contact with differentiated cells. Cultured adult mesenchymal stem cells showed some characteristics of synthetic state vascular smooth muscle cells (SMC). When co-cultured with vascular endothelial cells (EC) without cell contact, they exhibited abundant well-organised smooth muscle alpha-actin (alpha-actin) filaments. Direct co-culture with endothelial cells resulted in increased smooth muscle alpha-actin mRNA and protein, yet also comprehensive disruption of smooth muscle alpha-actin filament organisation. In order to assess whether these cell contact effects on mesenchymal stem cells were cell type specific, we also analysed direct co-cultures of mesenchymal stem cells with dermal fibroblasts. However, these experiments were characterised by the appearance of abundant spindle-shaped myofibroblast-like cells containing organised smooth muscle alpha-actin filaments. Thus, direct contact with distinct differentiated cells may be a critical determinant of mesenchymal stem cell fate in blood vessels and other connective tissues. PMID:15010334

Ball, Stephen G; Shuttleworth, Adrian C; Kielty, Cay M

2004-04-01

313

Stem Cells Promises to Keep?  

NSDL National Science Digital Library

Samantha and her husband Brad have two children, conceived with the help of in vitro fertilization treatments. After viewing a TV program on stem cells and their potential medical uses, Samantha is convinced that they should donate the remaining frozen embryos they have to medical research, an idea Brad strongly objects to. The case teaches about stem cells and their medical applications as well as the ethical dilemmas posed by their use.

Yaich, Lauren E.

2002-01-01

314

The stem cell debate CNN  

NSDL National Science Digital Library

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

2001-01-01

315

Two-photon imaging of stem cells  

Microsoft Academic Search

A variety of human and animal stem cells (rat and human adult pancreatic stem cells, salivary gland stem cells, dental pulpa stem cells) have been investigated by femtosecond laser 5D two-photon microscopy. Autofluorescence and second harmonic generation have been imaged with submicron spatial resolution, 270 ps temporal resolution, and 10 nm spectral resolution. In particular, NADH and flavoprotein fluorescence was

A. Uchugonova; E. Gorjup; I. Riemann; D. Sauer; K. König

2008-01-01

316

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

PubMed

The two paracrine melanogenic cytokines, stem cell factor (SCF) and endothelin-1 (ET-1), have been demonstrated to play pivotal roles in skin pigmentation including UVB-induced pigmentation and senile lentigo. However, little is known regarding their interactive effect on skin pigmentation. In order to investigate their roles in vivo, facultative pigmentation of human skin xenografts on severe combined immunodeficient (SCID) mice was assessed. After 1 week of acclimation in a pathogen-free barrier, dermatomed fresh cadaveric skin was surgically grafted onto the back of the mice and allowed to heal for 5-6 weeks prior to cytokine administration. Intradermal injections of SCF at 0.7 or 2.0 microg significantly increased skin pigmentation when compared to vehicle control. Despite the lack of a dose-dependent pigmentation response following ET-1 administration, the combination of 0.2 microg SCF and 0.1 microg ET-1 demonstrated a statistically significant increase in tyrosinase gene expression substantiated by the enhancement of melanin content and skin pigmentation compared to treatment with SCF alone or ET-1 alone. These findings establish an in vivo interaction between SCF and ET-1 with regard to their capacity to effect an increase in skin pigmentation. PMID:16940961

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

2006-11-01

317

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

PubMed Central

Abstract In recent years, terahertz radiation sources are increasingly being exploited in military and civil applications. However, only a few studies have so far been conducted to examine the biological effects associated with terahertz radiation. In this study, we evaluated the cellular response of mesenchymal mouse stem cells exposed to THz radiation. We apply low-power radiation from both a pulsed broad-band (centered at 10 THz) source and from a CW laser (2.52 THz) source. Modeling, empirical characterization, and monitoring techniques were applied to minimize the impact of radiation-induced increases in temperature. qRT-PCR was used to evaluate changes in the transcriptional activity of selected hyperthermic genes. We found that temperature increases were minimal, and that the differential expression of the investigated heat shock proteins (HSP105, HSP90, and CPR) was unaffected, while the expression of certain other genes (Adiponectin, GLUT4, and PPARG) showed clear effects of the THz irradiation after prolonged, broad-band exposure. PMID:21991556

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

2011-01-01

318

Effects of infrasound on the growth of bone marrow mesenchymal stem cells: A pilot study.  

PubMed

Poor viability of transplanted bone marrow mesenchymal stem cells (BMSCs) is well?known, but developing methods for enhancing the viability of BMSCs requires further investigation. The aim of the present study was to elucidate the effects of infrasound on the proliferation and apoptosis of BMSCs, and to determine the association between survivin expression levels and infrasound on BMSCs. Primary BMSCs were derived from Sprague Dawley rats. The BMSCs, used at passage three, were divided into groups that received infrasound for 10, 30, 60, 90 or 120 min, and control groups, which were exposed to the air for the same durations. Infrasound was found to promote proliferation and inhibit apoptosis in BMSCs. The results indicated that 60 min was the most suitable duration for applied infrasound treatment to BMSCs. The protein and mRNA expression levels of survivin in BMSCs from the two treatment groups that received 60 min infrasound or air, were examined by immunofluorescence and quantitative polymerase chain reaction. Significant differences in survivin expression levels were identified between the two groups, as infrasound enhanced the expression levels of survivin. In conclusion, infrasound promoted proliferation and inhibited apoptosis in BMSCs, and one mechanisms responsible for the protective effects may be the increased expression levels of survivin. PMID:25175368

He, Renhong; Fan, Jianzhong

2014-11-01

319

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

PubMed

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

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

2014-03-01

320

Effects of Vitamin A on In Vitro Maturation of Pre-Pubertal Mouse Spermatogonial Stem Cells  

PubMed Central

Testicular tissue cryopreservation is the only potential option for fertility preservation in pre-pubertal boys exposed to gonadotoxic treatment. Completion of spermatogenesis after in vitro maturation is one of the future uses of harvested testicular tissue. The purpose of the current study was to evaluate the effects of vitamin A on in vitro maturation of fresh and frozen-thawed mouse pre-pubertal spermatogonial stem cells in an organ culture system. Pre-pubertal CD1 mouse fresh testes were cultured for 7 (D7), 9 (D9) and 11 (D11) days using an organ culture system. Basal medium was supplemented with different concentrations of retinol (Re) or retinoic acid (RA) alone or in combination. Seminiferous tubule morphology (tubule diameter, intra-tubular cell type), intra-tubular cell death and proliferation (PCNA antibody) and testosterone level were assessed at D7, D9 and D11. Pre-pubertal mouse testicular tissue were frozen after a soaking temperature performed at -7°C, -8°C or -9°C and after thawing, were cultured for 9 days, using the culture medium preserving the best fresh tissue functionality. Retinoic acid at 10-6M and retinol at 3.3.10-7M, as well as retinol 10-6M are favourable for seminiferous tubule growth, maintenance of intra-tubular cell proliferation and germ cell differentiation of fresh pre-pubertal mouse spermatogonia. Structural and functional integrity of frozen-thawed testicular tissue appeared to be well-preserved after soaking temperature at -8°C, after 9 days of organotypic culture using 10-6M retinol. RA and Re can control in vitro germ cell proliferation and differentiation. Re at a concentration of 10-6M maintains intra-tubular cell proliferation and the ability of spermatogonia to initiate spermatogenesis in fresh and frozen pre-pubertal mouse testicular tissue using a soaking temperature at -8°C. Our data suggested a possible human application for in vitro maturation of cryopreserved pre-pubertal testicular tissue. PMID:24349372

Travers, Albanne; Arkoun, Brahim; Safsaf, Athmane; Milazzo, Jean-Pierre; Absyte, Anne; Bironneau, Amandine; Perdrix, Anne; Sibert, Louis; Mace, Bertrand; Cauliez, Bruno; Rives, Nathalie

2013-01-01

321

Cell Stem Cell Molecular Pathway and Cell State Responsible  

E-print Network

Cell Stem Cell Article Molecular Pathway and Cell State Responsible for Dissociation-Induced Apoptosis in Human Pluripotent Stem Cells Masatoshi Ohgushi,1,2 Michiru Matsumura,1,2 Mototsugu Eiraku,1 Sasai1,2,* 1Organogenesis and Neurogenesis Group 2Division of Human Stem Cell Technology 3Laboratory

South Bohemia, University of

322

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

323

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

E-print Network

1 EMBRYONIC STEM CELLS or INDUCED PLURIPOTENT STEM CELLS? A DNA INTEGRITY PERSPECTIVE Qiang Bai Gene Therapy 2013;13(2):93-8" #12;2 ABSTRACT Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical research

Boyer, Edmond

324

Columbia Stem Cell Initiative Tapping the potential of stem cells for human health  

E-print Network

Faculty Positions in Stem Cell Research at Columbia University Medical Center The Columbia Stem Cell of stem cells for human health. Their research covers all aspects of stem cell research, from basic Professor and Associate Professor level. Applicants' research may focus directly on stem cell biology

Adams, Mark

325

Curr Gene Ther . Author manuscript Embryonic stem cells or induced pluripotent stem cells? A DNA integrity  

E-print Network

Curr Gene Ther . Author manuscript Page /1 7 Embryonic stem cells or induced pluripotent stem cellsPSCs) and embryonic stem cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical ; Embryonic Stem Cells ; cytology ; immunology ; Epigenesis, Genetic ; Genomic Instability ; Humans ; Induced

Paris-Sud XI, Université de

326

Cell Stem Cell CNS-Resident Glial Progenitor/Stem Cells  

E-print Network

Cell Stem Cell Article CNS-Resident Glial Progenitor/Stem Cells Produce Schwann Cells as well. Richardson,3,4,* and Robin J.M. Franklin1,* 1MRC Cambridge Centre for Stem Cell Biology and RegenerativeResearch Department of Cell and Developmental Biology 5Research Department of Neuroscience, Physiology

Richardson, William D.

327

Are cancer stem cells radioresistant?  

PubMed Central

Based on findings that cancer cell clonogens exhibit stem cell features, it has been suggested that cancer stem-like cells are relatively radioresistant owing to different intrinsic and extrinsic factors, including quiescence, activated radiation response mechanisms (e.g., enhanced DNA repair, upregulated cell cycle control mechanisms and increased free-radical scavengers) and a surrounding microenvironment that enhances cell survival mechanisms (e.g., hypoxia and interaction with stromal elements). However, these radiosensitivity features are probably dynamic in nature and come into play at different times during the course of chemo/radiotherapy. Therefore, different molecularly targeted radiosensitization strategies may be needed at different stages of therapy. This article describes potential sensitization approaches based on the dynamics and changing properties of cancer stem-like cells during therapy. PMID:21062156

Hittelman, Walter N; Liao, Yong; Wang, Li; Milas, Luka

2011-01-01

328

Stem Cells and Calcium Signaling  

PubMed Central

The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached. Among these signals are transient changes in intracellular Ca2+ concentration [Ca2+]i. Acting as an intracellular messenger, Ca2+ has a key role in cell signaling pathways in various differentiation stages of stem cells. The aim of this chapter is to present a broad overview of various moments in which Ca2+-mediated signaling is essential for the maintenance of stem cells and for promoting their development and differentiation, also focusing on their therapeutic potential. PMID:22453975

Tonelli, Fernanda M.P.; Santos, Anderson K.; Gomes, Dawidson A.; da Silva, Saulo L.; Gomes, Katia N.; Ladeira, Luiz O.

2014-01-01

329

Cell Stem Cell Wnts as Self-Renewal Factors  

E-print Network

Cell Stem Cell Previews Wnts as Self-Renewal Factors: Mammary Stem Cells and Beyond Esther M, Burnaby, British Columbia V5A 1S6, Canada 2Hubrecht Institute for Developmental Biology and Stem Cell.clevers@hubrecht.eu DOI 10.1016/j.stem.2010.05.004 Adult stem cells hold great promise for regenerative medicine, yet

Verheyen, Esther M.

330

Gene and Stem Cell Therapy  

Microsoft Academic Search

Gene and stem cell therapy are being developed as novel treatments for cystic fibrosis (CF). In gene therapy, the therapeutic nucleic acid is delivered to terminally differentiated epithelial cells in the airways. While technically less demanding, this approach has the drawback that therapy must be continually re-administered because of target cell turnover. Direct airway administration is also faced with powerful

A. Boyd

2006-01-01

331

Stem Cells of Mammalian Brain: Biology of the Stem Cells in vivoand in vitro  

Microsoft Academic Search

Stem cells are totipotent cells of the blastocyst (embryonal stem cells) and multipotent germinative cells of ento-, ecto-, and mesoderm that give rise to all tissues during embryogenesis. The stem cells have high proliferation activity and an unlimited capacity for self-production by symmetrical mitosis. Asymmetrical mitosis of the stem cells generates daughter cells (“progenitor cells”) with unlimited proliferation potential. During

I. V. Viktorov

2001-01-01

332

Stem cells and diabetes  

Microsoft Academic Search

Diabetes mellitus is a metabolic disorder affecting 2–5% of the population. Transplantation of isolated islets of Langerhans from donor pancreata could be a cure for diabetes; however, such an approach is limited by the scarcity of the transplantation material and the long-term side effects of immunosuppressive therapy. These problems may be overcome by using a renewable source of cells, such

G Berná; T León-Quinto; R Enseñat-Waser; E Montanya; F Martín; B Soria

2001-01-01

333

What's missing? Discussing stem cell translational research in educational information on stem cell "tourism".  

PubMed

Stem cell tourism is a growing industry in which patients pursue unproven stem cell therapies for a wide variety of illnesses and conditions. It is a challenging market to regulate due to a number of factors including its international, online, direct-to-consumer approach. Calls to provide education and information to patients, their families, physicians, and the general public about the risks associated with stem cell tourism are mounting. Initial studies examining the perceptions of patients who have pursued stem cell tourism indicate many are highly critical of the research and regulatory systems in their home countries and believe them to be stagnant and unresponsive to patient needs. We suggest that educational material should include an explanation of the translational research process, in addition to other aspects of stem cell tourism, as one means to help promote greater understanding and, ideally, curb patient demand for unproven stem cell interventions. The material provided must stress that strong scientific research is required in order for therapies to be safe and have a greater chance at being effective. Through an analysis of educational material on stem cell tourism and translational stem cell research from patient groups and scientific societies, we describe essential elements that should be conveyed in educational material provided to patients. Although we support the broad dissemination of educational material on stem cell translational research, we also acknowledge that education may simply not be enough to engender patient and public trust in domestic research and regulatory systems. However, promoting patient autonomy by providing good quality information to patients so they can make better informed decisions is valuable in itself, irrespective of whether it serves as an effective deterrent of stem cell tourism. PMID:23581669

Master, Zubin; Zarzeczny, Amy; Rachul, Christen; Caulfield, Timothy

2013-01-01

334

Bioactive membranes for bone regeneration applications: effect of physical and biomolecular signals on mesenchymal stem cell behavior.  

PubMed

This study focuses on the in vitro characterization of bioactive elastin-like recombinamer (ELR) membranes for bone regeneration applications. Four bioactive ELRs exhibiting epitopes designed to promote mesenchymal stem cell adhesion (RGDS), endothelial cell adhesion (REDV), mineralization (HAP), and both cell adhesion and mineralization (HAP-RGDS) were synthesized using standard recombinant protein techniques. The materials were then used to fabricate ELR membranes incorporating a variety of topographical micropatterns including channels, holes and posts. Primary rat mesenchymal stem cells (rMSCs) were cultured on the different membranes and the effects of biomolecular and physical signals on cell adhesion, morphology, proliferation, and differentiation were evaluated. All results were analyzed using a custom-made MATLAB program for high throughput image analysis. Effects on cell morphology were mostly dependent on surface topography, while cell proliferation and cell differentiation were largely dependent on the biomolecular signaling from the ELR membranes. In particular, osteogenic differentiation (evaluated by staining for the osteoblastic marker osterix) was significantly enhanced on cells cultured on HAP membranes. Remarkably, cells growing on membranes containing the HAP sequence in non-osteogenic differentiation media exhibited significant up-regulation of the osteogenic marker as early as day 5, while those growing on fibronectin-coated glass in osteogenic differentiation media did not. These results are part of our ongoing effort to develop an optimized molecularly designed periosteal graft. PMID:24035887

Tejeda-Montes, Esther; Smith, Katherine H; Rebollo, Elena; Gómez, Raúl; Alonso, Matilde; Rodriguez-Cabello, J Carlos; Engel, Elisabeth; Mata, Alvaro

2014-01-01

335

EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Long-Term, Stable Differentiation of Human Embryonic Stem  

E-print Network

EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Long-Term, Stable Differentiation of Human Embryonic Stem Cell-Derived Neural Precursors Grafted into the Adult Mammalian Neostriatum IGOR NASONKIN Words. Cellular therapy · Embryonic stem cells · Neural differentiation · Neural induction · Neural stem

Ryugo, David K.

336

Types of Stem Cell Transplants for Treating Cancer  

MedlinePLUS

... of stem cells for transplant Types of stem cell transplants for treating cancer In a typical stem ... from your identical twin or triplet Autologous stem cell transplants These stem cells come from you alone. ...

337

25 YEARS OF EPIDERMAL STEM CELLS  

PubMed Central

This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The last 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell biology is discussed in this article. The challenges we still face in understanding epidermal stem cell include defining molecular markers for stem and progenitor subpopulations, determining the locations and contributions of the different stem cell niches, and mapping regulatory pathways of epidermal stem cell proliferation and differentiation. However, our rapidly evolving understanding of epidermal stem cells has many potential uses that promise to translate into improved patient therapy. PMID:22205306

Ghadially, Ruby

2012-01-01

338

Programmable mechanobioreactor for exploration of the effects of periodic vibratory stimulus on mesenchymal stem cell differentiation.  

PubMed

A programmable bioreactor using a voice-coil actuator was developed to enable research on the effects of periodic vibratory stimulus on human and porcine mesenchymal stem cells (MSCs). We hypothesized that low frequency vibrations would result in a cartilage phenotype and higher frequency vibrations would result in a bone phenotype. The mechanical stimulation protocol is adjusted from a computer external to the incubator via a USB cable. Once programmed, the embedded microprocessor and sensor system on the bioreactor execute the protocol independent of the computer. In each test, a sinusoidal stimulus was applied to a culture plate in 1-min intervals with a 15-min rest following each, for a total of 15?h per day for 10 days. Frequencies of 1 and 100?Hz were applied to cultures of both human and porcine umbilical cord-derived MSCs. Chondrogenesis was determined by Alcian blue staining for glycosaminoglycans and an increased differentiation index (ratio of mRNA for collagen II and collagen I). Osteogenic differentiation was indicated with Alizarin red for calcium staining and increased bone morphogenetic protein 2 mRNA. One-hertz stimulation resulted in a cartilage phenotype for both human and porcine MSCs, while 100-Hz stimulation resulted in a bone phenotype. PMID:24570842

Cashion, Avery T; Caballero, Montserrat; Halevi, Alexandra; Pappa, Andrew; Dennis, Robert G; van Aalst, John A

2014-02-01

339

Resveratrol Effect on Osteogenic Differentiation of Rat and Human Adipose Derived Stem Cells in a 3-D Culture Environment  

PubMed Central

The goal of this study was to investigate the effect of resveratrol treatment on the osteogenic potential of human and rat adipose derived stem cells in a 3-D culture environment. Adipose derived stem cells (ADSCs) have been widely studied and have shown promise as a potential source of osteogenic progenitor cells. Previous work had investigated the effect of 25 ?M resveratrol on the osteogenic differentiation of rat ADSCs in a 3-D environment and found that pre-treating cells for one passage prior to seeding on the scaffold yielded significantly more mineralization than untreated cells. We first sought to investigate whether this result was also observable with human ADSCs and found that the human cells did not respond to 25 ?M resveratrol in a positive manner suggesting a species specific difference in resveratrol dosage. Therefore we next investigated multiple doses at or below 25 ?M resveratrol for both rat and human ADSCs. We found that doses below 25 ?M caused significantly more mineralization than 0 (untreated) and 25 ?M treated cells in a 3-D culture environment. Further, we observed species differences in the total amount of mineralized matrix, as well as the mean mineral density suggesting that the nature of mineralization of the extracellular matrix was different between species. Histological examination of the scaffolds showed that the human cell constructs remain highly cellular in nature with small pockets of mineralization; while rat cell constructs showed much larger and more mature mineralized nodules. Taken together we demonstrate dose dependent differences in the mineralization response of human and rat ADSCs to resveratrol treatment, suggesting that in vitro pre-conditioning of 3D adipose-derived stem cell constructs may be an effective strategy to promote osteogenic differentiation prior to implantation. PMID:22658160

Dosier, Christopher R.; Erdman, Christopher P.; Park, Jung Hwa; Schwartz, Zvi; Boyan, Barbara D.; Guldberg, Robert E.

2011-01-01

340

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

PubMed

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

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

2010-01-01

341

Storage of Adipose Stem Cells  

Microsoft Academic Search

\\u000a Adipose-derived stem cells (ADSCs) are becoming the cells of choice for an increasing number of clinical trials, and they\\u000a promise to be in the next decade the preferential cell type used in cell therapies. Here we describe how they can be isolated\\u000a from adipose tissue, prepared for storage, and eventually conserved in liquid nitrogen, waiting for future cell therapy applications.

Giorgio Bronz; Gianni Soldati

342

Effects of Age and Heart Failure on Human Cardiac Stem Cell Function  

PubMed Central

Currently, it is unknown whether defects in stem cell growth and differentiation contribute to myocardial aging and chronic heart failure (CHF), and whether a compartment of functional human cardiac stem cells (hCSCs) persists in the decompensated heart. To determine whether aging and CHF are critical determinants of the loss in growth reserve of the heart, the properties of hCSCs were evaluated in 18 control and 23 explanted hearts. Age and CHF showed a progressive decrease in functionally competent hCSCs. Chronological age was a major predictor of five biomarkers of hCSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21Cip1 and p16INK4a expression. CHF had similar consequences for hCSCs, suggesting that defects in the balance between cardiomyocyte mass and the pool of nonsenescent hCSCs may condition the evolution of the decompensated myopathy. A correlation was found previously between telomere length in circulating bone marrow cells and cardiovascular diseases, but that analysis was restricted to average telomere length in a cell population, neglecting the fact that telomere attrition does not occur uniformly in all cells. The present study provides the first demonstration that dysfunctional telomeres in hCSCs are biomarkers of aging and heart failure. The biomarkers of cellular senescence identified here can be used to define the birth date of hCSCs and to sort young cells with potential therapeutic efficacy. PMID:21703415

Cesselli, Daniela; Beltrami, Antonio P.; D'Aurizio, Federica; Marcon, Patrizia; Bergamin, Natascha; Toffoletto, Barbara; Pandolfi, Maura; Puppato, Elisa; Marino, Laura; Signore, Sergio; Livi, Ugolino; Verardo, Roberto; Piazza, Silvano; Marchionni, Luigi; Fiorini, Claudia; Schneider, Claudio; Hosoda, Toru; Rota, Marcello; Kajstura, Jan; Anversa, Piero; Beltrami, Carlo A.; Leri, Annarosa

2011-01-01

343

Effects of methylmercury exposure on neuronal differentiation of mouse and human embryonic stem cells.  

PubMed

The establishment of more efficient in vitro approaches has been widely acknowledged as a critical need for toxicity testing. In this study, we examined the effects of methylmercury (MeHg), which is a well-known developmental neurotoxicant, in two neuronal differentiation systems of mouse and human embryonic stem cells (mESCs and hESCs, respectively). Embryoid bodies were generated from gathering of mESCs and hESCs using a micro-device and seeded onto ornithine-laminin-coated plates to promote proliferation and neuronal differentiation. The cells were exposed to MeHg from the start of neuronal induction until the termination of cultures, and significant reductions of mESCs and hESCs were observed in the cell viability assays at 1,10,100 and 1000nM, respectively. Although the mESC derivatives were more sensitive than the hESC derivatives to MeHg exposure in terms of cell viability, the morphological evaluation demonstrated that the neurite length and branch points of hESC derivatives were more susceptible to a low concentration of MeHg. Then, the mRNA levels of differentiation markers were examined using quantitative RT-PCR analysis and the interactions between MeHg exposure and gene expression levels were visualized using a network model based on a Bayesian algorithm. The Bayesian network analysis showed that a MeHg-node was located on the highest hierarchy in the hESC derivatives, but not in the mESC derivatives, suggesting that MeHg directly affect differentiation marker genes in hESCs. Taken together, effects of MeHg were observed in our neuronal differentiation systems of mESCs and hESCs using a combination of morphological and molecular markers. Our study provided possible, but limited, evidences that human ESC models might be more sensitive in particular endpoints in response to MeHg exposure than that in mouse ESC models. Further investigations that expand on the findings of the present paper may solve problems that occur when the outcomes from laboratory animals are extrapolated for human risk evaluation. PMID:22555245

He, Xiaoming; Imanishi, Satoshi; Sone, Hideko; Nagano, Reiko; Qin, Xian-Yang; Yoshinaga, Jun; Akanuma, Hiromi; Yamane, Junko; Fujibuchi, Wataru; Ohsako, Seiichiroh

2012-07-01

344

Stem Cell Therapy for Ischemic Heart Disease  

PubMed Central

Abstract Stem cell transplantation has emerged as a novel treatment option for ischemic heart disease. Different cell types have been utilized and the recent development of induced pluripotent stem cells has generated tremendous excitement in the regenerative field. Bone marrow-derived multipotent progenitor cell transplantation in preclinical large animal models of postinfarction left ventricular remodeling has demonstrated long-term functional and bioenergetic improvement. These beneficial effects are observed despite no significant engraftment of bone marrow cells in the myocardium and even lower differentiation of these cells into cardiomyocytes. It is thought to be related to the paracrine effect of these stem cells, which secrete factors that lead to long-term gene expression changes in the host myocardium, thereby promoting neovascularization, inhibiting apoptosis, and stimulating resident cardiac progenitor cells. Future studies are warranted to examine the changes in the recipient myocardium after stem cell transplantation and to investigate the signaling pathways involved in these effects. Antioxid. Redox Signal. 13, 1879–1897. PMID:20687781

Jameel, Mohammad Nurulqadr

2010-01-01

345

Stem cells as vectors for antitumour therapy  

Microsoft Academic Search

Recent research suggests that mesenchymal stem cells (MSCs) are able to migrate specifically to tumours and their metastases throughout the body. This has led to considerable excitement about the possibility of modifying these cells to express anticancer molecules and using them as specific targeted anticancer agents. However, there are concerns that systemically delivered MSCs may have non-desirable effects, and there

Michael R Loebinger; Sam M Janes

2010-01-01

346

Stem cells and nuclear reprogramming.  

PubMed

Derivation of human embryonic stem (ES) cells from preimplantation embryos ten years ago raised great hopes that they may be an excellent source of cells for cell replacement therapy. However, serious ethical concerns and the risk of immune rejection of allotransplanted cells have hindered the translation of ES cell-based therapies into the clinic. In an attempt to circumvent these barriers, a number of methods have been developed for converting adult somatic cells into a pluripotent state from which ethically acceptable patient-specific mature cells of interest could be derived. These efforts, backed by advances in elucidating the molecular basis of pluripotency, have culminated in successful reprogramming of fibroblasts into ES cell-like cells, termed induced pluripotent stem (iPS) cells, by ectopic expression of only a handful of "stemness" factors. iPS cells possess morphological, molecular and developmental features of conventional blastocyst-derived ES cells and have the potential to serve as a source of therapeutic cells for customized tissue repair, gene therapy, drug discovery, toxicological testing and for studying the molecular basis of human disease. The goal of this review is to provide the current state-of-the-art in this very exciting and dynamic field and to discuss barriers that remain to be removed before the therapeutic potential of iPS cells can be fully realized. PMID:18465442

Saric, Tomo; Hescheler, Juergen

2008-01-01

347

Expansion of mammalian neural stem cells in bioreactors: effect of power input and medium viscosity.  

PubMed

Multipotent neural precursors can be cultured in suspension bioreactors as aggregates of stem cells and progenitor cells. However, it is important to limit the size of the aggregates, as necrotic centers may develop at very large diameters. Previously, we have shown that the hydrodynamics within a suspension bioreactor can be used to control the diameter of NSC aggregates (D(MAVG)<150 microm) below sizes where necrosis would be expected to occur. In the present study, power law correlations were developed for our bioreactors showing the dependence of the maximum mean aggregate diameter on both the kinematic viscosity of the medium and the power input per unit mass of medium. The power input was manipulated by changing the agitation rate (60-100 rpm), and the viscosity was manipulated through the addition of non-toxic levels of carboxymethylcellulose. The study also confirmed that the maximum liquid shear generated at the surface of the aggregates was sufficient to dislodge single cells, thus limiting the maximum diameter of the aggregates, without causing cell damage (tau(max)=9.76 dyn/cm(2)). This is a first step in the development of a reproducible, scaled-up process for the production of neural stem cells for therapeutic applications including the treatment of neurodegenerative disorders and acute central nervous system injuries. PMID:11947941

Sen, Arindom; Kallos, Michael S; Behie, Leo A

2002-03-31

348

Reconstructing the stem cell debate.  

PubMed

Human embryonic stem cells have been a major topic in science, medicine, and religion since their discovery in 1998. However, due to the complex discourse and rhetoric of scientific language, debate has remained within the professional realm via "expert bioethics." Using the tenets of pragmatism, the author examines the need to move the debate to society as a whole and disentangle the stem cell debate from the ideologies of the human cloning and abortion debates. Opening this issue to a societal debate will advance societal growth, resulting in informed decisions on moral issues, funding, or regulation associated with hES cell research. PMID:12755109

Sitko, Bradley J

2002-01-01

349

The effect of high frequency electric field on enhancement of chondrogenesis in human adipose-derived stem cells  

PubMed Central

Objective(s): Osteoarthritis (OA) is globally one of the most common diseases from the middle age onwards. Cartilage is an avascular tissue therefore it cannot be repaired in the body. Conservative treatments have failed as a good remedy and cell therapy as a decisive cure is needed. One of the best and easily accessible cell sources for this purpose is adipose-derived stem cells which can be differentiated into chondrocytes by tissue engineering techniques. Chemical and physical inducers have a key role in stem cell - chondrocyte differentiation. We have tried to determine the role of electric fields (EF) in promoting this kind of chondrogenesis process. Materials and Methods: Human adipose derived stem cells (ADSCs) were extracted from subcutaneous abdominal adipose tissue during cesarean section. A high frequency (60 KHz) EF (20 mv/cm), as a physical inducer for chondrogenesis in a 3D micromass culture system of ADSCs was utilized. Also, MTT, ELISA, flow cytometry, and real-time PCR techniques were used for this study. Results: We found that using physical electric fields leads to chondrogenesis. Furthermore, results show that using both physical (EF) and chemical (TGF?3) inducers simultaneously, has best outcomes in chondrogenesis, and expression of SOX9 and type II collagen genes. It also causes significant decreased expression of type I and X collagen genes in pure EF group compared with control group. Conclusion: The EF was found as a proper effective inducer in chondrogenic differentiation of human ADSCs micromass culture.

Esfandiari, Ebrahim; Roshankhah, Shiva; Mardani, Mohammad; Hashemibeni, Batool; Naghsh, Erfan; Kazemi, Mohammad; Salahshoor, Mohammadreza

2014-01-01

350

Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model.  

PubMed

Treatment of myocardial infarction (MI) with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal MI models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of MI using a fully grown non-immune-compromised rat model. Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were randomized to receive intramyocardial injections of adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, or phosphate-buffered saline 1 week following induction of MI. After 4 weeks, left ventricular ejection fraction (LVEF) was improved in the adipose-derived stem cell group, and scar wall thickness was greater compared with the saline group. Adipose-derived as well as bone marrow-derived mesenchymal stem cells prevented left ventricular end diastolic dilation. Neither of the cell groups displayed increased angiogenesis in the myocardium compared with the saline group. Adipose-derived stem cells from a human ischemic patient preserved cardiac function following MI, whereas this could not be demonstrated for bone marrow-derived mesenchymal stem cells, with only adipose-derived stem cells leading to an improvement in LVEF. Neither of the stem cell types induced myocardial angiogenesis, raising the question whether donor age and health have an effect on the efficacy of stem cells used in the treatment of MI. PMID:23211469

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Holst-Hansen, Claus; Kastrup, Jens; Baandrup, Ulrik; Zachar, Vladimir; Fink, Trine; Simonsen, Ulf

2014-02-01

351

Retroviral Expression in Embryonic Stem Cells and Hematopoietic Stem Cells  

PubMed Central

Achieving long-term retroviral expression in primary cells has been problematic. De novo DNA methylation of infecting proviruses has been proposed as a major cause of this transcriptional repression. Here we report the development of a mouse stem cell virus (MSCV) long terminal repeat-based retroviral vector that is expressed in both embryonic stem (ES) cells and hematopoietic stem (HS) cells. Infected HS cells and their differentiated descendants maintained long-term and stable retroviral expression after serial adoptive transfers. In addition, retrovirally infected ES cells showed detectable expression level of the green fluorescent protein (GFP). Moreover, GFP expression of integrated proviruses was maintained after in vitro differentiation of infected ES cells. Long-term passage of infected ES cells resulted in methylation-mediated silencing, while short-term expression was methylation independent. Tissues of transgenic animals, which we derived from ES cells carrying the MSCV-based provirus, did not express GFP. However, treatment with the demethylating agent 5-azadeoxycytidine reactivated the silent provirus, demonstrating that DNA methylation is involved in the maintenance of retroviral repression. Our results indicate that retroviral expression in ES cells is repressed by methylation-dependent as well as methylation-independent mechanisms. PMID:11003639

Cherry, Sara R.; Biniszkiewicz, D.; van Parijs, L.; Baltimore, D.; Jaenisch, R.

2000-01-01

352

Stem-cell ecology and stem cells in motion  

PubMed Central

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

Scadden, David T.

2008-01-01

353

Stem cell differentiation: Sticky mechanical memory  

NASA Astrophysics Data System (ADS)

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

Eyckmans, Jeroen; Chen, Christopher S.

2014-06-01

354

Enabling Stem Cell Research and Development  

E-print Network

to an optimal global solution for stem cell R&D. Relying onstem cell materials in existence, in order to identify where new solutionssolutions. Membership may be defined simply as institutions that are “engaged in stem cell

Saha, Krishanu; Graff, Gregory; Winickoff, David

2007-01-01

355

Control of the Embryonic Stem Cell State  

E-print Network

Embryonic stem cells and induced pluripotent stem cells hold great promise for regenerative medicine. These cells can be propagated in culture in an undifferentiated state but can be induced to differentiate into specialized ...

Young, Richard A.

356

Modulation of ?-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal  

PubMed Central

Wnt/?-catenin signalling has a variety of roles in regulating stem cell fates. Its specific role in mouse epiblast stem cell self-renewal, however, remains poorly understood. Here we show that Wnt/?-catenin functions in both self-renewal and differentiation in mouse epiblast stem cells. Stabilization and nuclear translocation of ?-catenin and its subsequent binding to T-cell factors induces differentiation. Conversely, retention of stabilized ?-catenin in the cytoplasm maintains self-renewal. Cytoplasmic retention of ?-catenin is effected by stabilization of Axin2, a downstream target of ?-catenin, or by genetic modifications to ?-catenin that prevent its nuclear translocation. We also find that human embryonic stem cell and mouse epiblast stem cell fates are regulated by ?-catenin through similar mechanisms. Our results elucidate a new role for ?-catenin in stem cell self-renewal that is independent of its transcriptional activity and will have broad implications in understanding the molecular regulation of stem cell fate. PMID:23985566

Kim, Hoon; Wu, Jun; Ye, Shoudong; Tai, Chih-I; Zhou, Xingliang; Yan, Hexin; Li, Ping; Pera, Martin; Ying, Qi-Long

2014-01-01

357

Human stem cell ethics: beyond the embryo.  

PubMed

Human embryonic stem cell research has elicited powerful debates about the morality of destroying human embryos. However, there are important ethical issues related to stem cell research that are unrelated to embryo destruction. These include particular issues involving different types of cells used, the procurement of such cells, in vivo use of stem cells, intellectual property, and conflicts of interest. PMID:18522846

Sugarman, Jeremy

2008-06-01

358

Patenting Human Genes and Stem Cells  

Microsoft Academic Search

Cell lines and genetically modified single cell organisms have been considered patentable subjects for the last two decades. However, despite the technical patentability of genes and stem cell lines, social and legal controversy concerning their 'ownership' has surrounded stem cell research in recent years. Some granted patents on stem cells with extremely broad claims are casting a shadow over the

Enca Martin-Rendon; Derek J. Blake

2007-01-01

359

Hypoxia and Regulation of Cancer Cell Stemness  

PubMed Central

Spontaneous tumors often contain heterogeneous populations of tumor cells with different tumor-initiating potentials or cancer cellstemness.” Clonal heterogeneity can be traced to specific locations inside a tumor where clones with different metastatic capabilities are identified, suggesting that the tumor microenvironment can exert a significant effect on the evolution of different clonal populations. Hypoxia is a common feature of tumor microenvironments and has the potential to facilitate malignant progression. This chapter provides a synopsis of hypoxia-regulated pathways implicated in the maintenance of cancer stem cells. PMID:24272353

Lin, Qun

2014-01-01

360

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

NASA Astrophysics Data System (ADS)

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

Casey, Meghan E.

361

Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment  

PubMed Central

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e. the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to: (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. Here, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering. PMID:22101755

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-01-01

362

Engineering approaches toward deconstructing and controlling the stem cell environment.  

PubMed

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e., the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. In this article, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering. PMID:22101755

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-06-01

363

Stem Cell Reports CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells  

E-print Network

Stem Cell Reports Report CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex cell behavior. Here, we identify CRIPTO and its cell- surface receptor GRP78 as regulators of stem cell differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast

Wahl, Geoffrey M.

364

The effect of purmorphamine and sirolimus on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.  

PubMed

Small molecules have been introduced as less expensive biologically active compounds that can regulate different developmental phenomena. Purmorphamine and sirolimus are two small molecules that, according to some studies, possess certain osteomodulatory effects. This study was set out to highlight the appropriate dose and response time of these small molecules on enhancement of osteogenesis in human bone marrow-derived mesenchymal stem cells from early to mid and late stages of differentiation. Alkaline phosphatase activity, matrix mineralization and expression of osteoblast genes were quantitatively assessed in vitro. For the in vivo study, we transplanted stem cell-based constructs subcutaneously into rats, and treated them daily with the most promising doses of the small molecule. The constructs were analyzed by real-time PCR and histological staining. Our results showed that Sirolimus reduced osteogenic differentiation of mesenchymal stem cells by decreasing alkaline phosphatase activity at dose of 100nM after 14 days and mineralization of the matrix at 14 and 21 days post-induction. Purmorphamine induced up-regulation of alkaline phosphatase activity and expression of RUNX-2 at day 14. Up-regulation of osteocalcin was detected at the 3 and 5?M doses of purmorphamine on day 14 post-induction. Matrix mineralization remained unchanged in the presence or absence of purmorphamine. This dose of small molecule also accelerated expression of Alkaline phosphatase transcripts in vivo. In conclusion, sirolimus had an inhibitory effect on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells; while purmorphamine, particularly at a dose of 3?M, showed a promotive effect in vitro and in vivo. PMID:23228449

Faghihi, F; Baghaban Eslaminejad, M; Nekookar, A; Najar, M; Salekdeh, G H

2013-02-01

365

Standardized cryopreservation of pluripotent stem cells.  

PubMed

The successful exploitation of human cells for research, translational, therapeutic, and commercial purposes requires that effective and simple cryopreservation methods be applied for storage in local and master cell banks. Of all the cell types utilized in modern research, human embryonic stem cells and their more recent relatives, induced pluripotent stem cells, are two of the most sensitive to cryopreservation. It is frequently observed that the lack of quality control and proper processing techniques yield poor recovery of pluripotent stem cells. The procedures in this unit have been optimized for handling some of the most recalcitrant stem cell lines, and provide a method for controlled-rate freezing, using minimal equipment that affords levels of cell viability comparable to expensive controlled-rate freezers. The protocol also eliminates the requirement for isopropanol, avoiding the hazards, on-going cost, and inconsistencies associated with its use and disposal. It provides a clinically relevant, inexpensive, reliable, and user-friendly method that successfully prepares cells for long-term cold storage and ensures maximum levels of cell viability post thaw. PMID:24510767

Cohen, Rick I; Thompson, Maria L; Schryver, Brian; Ehrhardt, Rolf O

2014-01-01

366

The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds  

PubMed Central

Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals Adult healthy beagle dogs (n = 10; 3–6 years old; 7.2–13.1 kg) were studied. Methods Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and ?-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-?, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. Results Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-?) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). Conclusion and clinical importance Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing. Résumé Contexte Les cellules souches adultes ont été largement étudiées dans les approches de bio-ingénierie pour la thérapie de réparation tissulaire. Nous évaluons l'efficacité clinique et la sécurité de l'application de cellules souches mésenchymateuses allogéniques en culture dérivées de moelle osseuse (MSCs) pour le traitement de plaies cutanées dans un modèle canin. Hypothèse La transplantation de MSC allogénique topique peut accélérer la fermeture en toute épaisseur de plaies cutanées expérimentales et atténuer l'inflammation locale. Sujets Des chiens beagles adultes sains (n = 10; 3–6 ans; 7.2–13.1 kg) ont été étudiés. Méthodes Des plaies cutanées en pleine épaisseur ont été crées sur la face dorsale des beagles sains et des MSCs allogènes ont été injectées par voie intradermique. Le taux de cicatrisation et le degré de production de collagène ont été analysés sur le plan histologique par colorations à l'hématoxyline et éosine et par trichrome. Le degré de prolifération cellulaire et d'angiogénèse ont été évalués par immunohistochimie à l'aide d'anticorps spécifiques d'antigène nucléaire de prolifération cellulaire, de vimentine et d'actine de muscle lisse ?. Les taux d'expression local d'ARNm d'interleukine-2, d'interféron-?, du facteur de croissance basique de fibroblaste et de métalloprotéinase-2 de matrice, ont été évalués par RT-PCR. Résultats Comparé avec les plaies traitées par excipient, les plaies traitées par les MSCs ont montré une plus rapide cicatrisation et une augmentation de synthèse de collagène, de prolifération cellulaire er d'angiogénèse. En outre, Les plaies traitées au MSC ont montré une expression diminuée de cytokines pro-inflammatoires (interleukine-2 et interféron-?) et des facteurs liés à la cicatrisation (facteur de croissance basique de fibrob

Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S; Jung, Dong-In; Park, Hee-Myung

2013-01-01

367

HIV and Stem Cell Transplantation.  

PubMed

In human immunodeficiency virus (HIV)-infected persons, the incidence of hematologic malignancies, including leukemia and lymphoma, is increased despite the use of successful antiretroviral therapy. Hematopoietic stem cell transplantation (SCT) is emerging as a safe and effective therapy for HIV-infected persons with hematologic malignancies. Management of these patients is complicated by drug-drug interactions involving antiretroviral therapy (ART) that may impact conditioning agent efficacy and metabolism of immunosuppressive medications and potentiate drug toxicities. As such, optimal strategies for ART remain controversial. We discuss recent advances, controversies, and future directions related to SCT in HIV-infected persons, including the investigation of allogeneic SCT as a strategy for HIV cure. PMID:25120135

Echenique, Ignacio A; Nelson, George E; Stosor, Valentina; Durand, Christine M

2014-09-01

368

Generation of Lymphohematopoietic Cells from Embryonic Stem Cells in Culture  

Microsoft Academic Search

An efficient system was developed that induced the differentiation of embryonic stem (ES) cells into blood cells of erythroid, myeloid, and B cell lineages by coculture with the stromal cell line OP9. This cell line does not express functional macrophage colony-stimulating factor (M-CSF). The presence of M-CSF had inhibitory effects on the differentiation of ES cells to blood cells other

Toru Nakano; Hiroaki Kodama; Tasuku Honjo

1994-01-01

369

Differential Effects of X-Rays and High-Energy {sup 56}Fe Ions on Human Mesenchymal Stem Cells  

SciTech Connect

Purpose: Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high-linear energy transfer (LET) {sup 56}Fe ions on human mesenchymal stem cells (hMSC). Methods and Materials: A multi-functional comparison was carried out to investigate the differential effects of X-rays and {sup 56}Fe ions on hMSC. The end points included modulation of key markers such as p53, cell cycle progression, osteogenic differentiation, and pathway and networks through transcriptomic profiling and bioinformatics analysis. Results: X-rays and {sup 56}Fe ions differentially inhibited the cell cycle progression of hMSC in a p53-dependent manner without impairing their in vitro osteogenic differentiation process. Pathway and network analyses revealed that cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy) X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched for high-dose (1 Gy) X-rays and {sup 56}Fe ions, with more significant effects from {sup 56}Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy {sup 56}Fe ions than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former while not for the latter. Conclusions: {sup 56}Fe ions exert more significant effects on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this study provides new mechanistic understandings of the relative health risks associated with low- and high-dose X-rays and high-LET space radiation.

Kurpinski, Kyle [Department of Bioengineering, University of California-Berkeley, Berkeley, CA (United States); Jang, Deok-Jin; Bhattacharya, Sanchita; Rydberg, Bjorn [Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Chu, Julia; So, Joanna [Department of Bioengineering, University of California-Berkeley, Berkeley, CA (United States); Wyrobek, Andy [Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Li Song [Department of Bioengineering, University of California-Berkeley, Berkeley, CA (United States); Wang Daojing [Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States)], E-mail: djwang@lbl.gov

2009-03-01

370

Effects of induction with novel agents versus conventional chemotherapy on mobilization and autologous stem cell transplant outcomes in multiple myeloma.  

PubMed

Multiple myeloma (MM) is the top indication for high-dose chemotherapy (HDC) with autologous stem cell transplantation (SCT), a strategy which improves progression-free survival and potentially overall survival (OS). Novel induction regimens incorporating the immunomodulatory (IMID) agents, such as thalidomide and lenalidomide and the proteosome inhibitor bortezomib improve response rates and survival for newly diagnosed patients. Recent data temper enthusiasm for these treatments by illustrating difficulty in some circumstances with mobilizing CD34(+) hematopoietic stem cells for subsequent HDC/SCT. We compare conventional induction regimens with novel agent-based induction strategies and the associated effects on stem cell mobilization and HDC/SCT outcome in 224 patients. Although patients exposed to novel agent inductions collected generally fewer CD34(+) cells than patients induced with chemotherapy, these differences did not translate into adverse consequences with subsequent HDC/SCT. We show that an improvement in OS after HDC/SCT may be related to induction therapy with novel agents as opposed to chemotherapy. Our data extrapolate on prior work and expand on ongoing controversies about optimal induction regimens for patients with MM planned for subsequent HDC/SCT and optimal sequencing of therapies. PMID:20038230

Benson, Don M; Panzner, Kathryn; Hamadani, Mehdi; Hofmeister, Craig C; Bakan, Courtney E; Smith, Megan K; Elder, Pat; Krugh, David; O'Donnell, Lynn; Devine, Steven M

2010-02-01

371

Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1.  

PubMed

The human immune system can be reconstituted in experimental animals by transplanting human hematopoietic stem cells (hHSCs) into immunodeficient mice. To generate such humanized mice, further improvements are required, particularly to ensure that transplanted hHSCs are maintained in mice and proliferate long enough to follow prolonged immune responses to chronic diseases or monitor therapeutic effects. To prepare the relatively human bone marrow environment in mice, we generated nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor gamma chain null (NOG) mice expressing human Jagged1 (hJ1) in an osteoblast-specific manner (hJ1-NOG mice) to examine whether Notch signaling induced by hJ1 mediates hHSC proliferation and/or maintenance in mice. The established hJ1-NOG mice possess relatively larger bone marrow space and thinner cortical bone compared with nontransgenic littermates, but the number of c-kit(+) Sca-1(+) lineage(-) cells was not significantly different between hJ1-NOG and nontransgenic littermates. In the transplantation experiments of CD34(+) cells obtained from human cord blood, CD34(+)CD38(-) cells (hHSCs) were more increased in hJ1-NOG recipient mice than in nontransgenic littermates in mouse bone marrow environment. In contrast, the transplanted mouse c-kit(+) Sca-1(+) lineage(-) cells did not show significant increase in the same hJ1-NOG mice. These results suggest that hJ1-NOG mice could contribute to the growth of transplanted human CD34(+) cells in a human-specific manner and be useful to study the in vivo behavior and/or development of human stem cells, including cancer stem cells and immune cells. PMID:24530466

Negishi, Naoko; Suzuki, Daisuke; Ito, Ryoji; Irie, Naoko; Matsuo, Koichi; Yahata, Takashi; Nagano, Kenichi; Aoki, Kazuhiro; Ohya, Keiichi; Hozumi, Katsuto; Ando, Kiyoshi; Tamaoki, Norikazu; Ito, Mamoru; Habu, Sonoko

2014-06-01

372

Conversion of adult mouse unipotent germline stem cells into pluripotent stem cells  

Microsoft Academic Search

Germline stem cells (GSCs), often called spermatogonial stem cells, are unipotent stem cells that can give rise only to gametes. Under defined culture conditions, unipotent GSCs can be converted into pluripotent stem cells, termed as germline-derived pluripotent stem (gPS) cells. gPS cells can be differentiated into cells forming all three germ layers and germ cells. In this study, we describe

Kinarm Ko; Marcos J Araúzo-Bravo; Julee Kim; Martin Stehling; Hans R Schöler

2010-01-01

373

Cryoprotective effects of low-density lipoproteins, trehalose and soybean lecithin on murine spermatogonial stem cells.  

PubMed

Summary Spermatogonial stem cells (SSCs) have the ability to self-renew and offer a pathway for genetic engineering of the male germ line. Cryopreservation of SSCs has potential value for the treatment of male infertility, spermatogonial transplantation, and so on. In order to investigate the cryopreservation effects of different cryoprotectants on murine SSCs, 0.2 M of low-density lipoproteins (LDL), trehalose and soybean lecithin were added to the cryoprotective medium, respectively, and the murine SSCs were frozen at -80°C or -196°C. The results indicated that the optimal recovery rates of murine SSCs in the cryoprotective medium supplemented with LDL, trehalose and soybean lecithin were 92.53, 76.35 and 75.48% at -80°C, respectively. Compared with freezing at -196°C, the optimum temperature for improvement of recovery rates of frozen murine SSCs, cryopreservation in three different cryoprotectants at -80°C, were 17.11, 6.68 and 10.44% respectively. The recovery rates of murine SSCs in the cryoprotective medium supplemented with 0.2 M LDL were significantly higher than that of other cryoprotectants (P < 0.05). Moreover, the recovery rates were demonstrated to be greater at -80°C compared with at -196°C (P < 0.05). In conclusion, 0.2 M of LDL could significantly protect murine SSCs at -80°C. In the freezing-thawing process, LDL is responsible for the cryopreservation of murine SSCs because it can form a protective film at the surface of membranes. However, more research is needed to evaluate and understand the precise role of LDL during the freezing-thawing of SSCs. PMID:22974447

Wang, Peng; Li, Ying; Hu, Xiao-Chen; Cai, Xiao-Li; Hou, Li-Peng; Wang, Yan-Feng; Hu, Jian-Hong; Li, Qing-Wang; Suo, Li-Juan; Fan, Zhi-Guo; Zhang, Bo

2014-05-01

374

The Warburg effect version 2.0: metabolic reprogramming of cancer stem cells.  

PubMed

When fighting cancer, knowledge on metabolism has always been important. Today, it matters more than ever. The restricted cataloging of cancer genomes is quite unlikely to achieve the task of curing cancer, unless it is integrated into metabolic networks that respond to and influence the constantly evolving cancer stem cell (CSC) cellular states. Once the genomic era of carcinogenesis had pushed the 1920s Otto Warburg's metabolic cancer hypothesis into obscurity for decades, the most recent studies begin to support a new developing paradigm, in which the molecular logic behind the conversion of non-CSCs into CSCs can be better understood in terms of the "metabolic facilitators" and "metabolic impediments" that operate as proximate openings and roadblocks, respectively, for the transcriptional events and signal transduction programs that ultimately orchestrate the intrinsic and/or microenvironmental paths to CSC cellular states. Here we propose that a profound understanding of how human carcinomas install a proper "Warburg effect version 2.0" allowing them to "run" the CSCs' "software" programs should guide a new era of metabolo-genomic-personalized cancer medicine. By viewing metabolic reprogramming of CSCs as an essential characteristic that allows dynamic, multidimensional and evolving cancer populations to compete successfully for their expansion on the organism, we now argue that CSCs bioenergetics might be another cancer hallmark. A definitive understanding of metabolic reprogramming in CSCs may complement or to some extent replace, the 30-y-old paradigm of targeting oncogenes to treat human carcinomas, because it can be possible to metabolically create non-permissive or "hostile" metabotypes to prevent the occurrence of CSC cellular states with tumor- and metastasis-initiating capacity. PMID:23549172

Menendez, Javier A; Joven, Jorge; Cufí, Sílvia; Corominas-Faja, Bruna; Oliveras-Ferraros, Cristina; Cuyàs, Elisabet; Martin-Castillo, Begoña; López-Bonet, Eugeni; Alarcón, Tomás; Vazquez-Martin, Alejandro

2013-04-15

375

Cryopreservation of Human Stem Cells for Clinical Application: A Review  

PubMed Central

Summary Stem cells have been used in a clinical setting for many years. Haematopoietic stem cells have been used for the treatment of both haematological and non-haematological disease; while more recently mesenchymal stem cells derived from bone marrow have been the subject of both laboratory and early clinical studies. Whilst these cells show both multipotency and expansion potential, they nonetheless do not form stable cell lines in culture which is likely to limit the breadth of their application in the field of regenerative medicine. Human embryonic stem cells are pluripotent cells, capable of forming stable cell lines which retain the capacity to differentiate into cells from all three germ layers. This makes them of special significance in both regenerative medicine and toxicology. Induced pluripotent stem (iPS) cells may also provide a similar breadth of utility without some of the confounding ethical issues surrounding embryonic stem cells. An essential pre-requisite to the commercial and clinical application of stem cells are suitable cryopreservation protocols for long-term storage. Whilst effective methods for cryopreservation and storage have been developed for haematopoietic and mesenchymal stem cells, embryonic cells and iPS cells have proved more refractory. This paper reviews the current state of cryopreservation as it pertains to stem cells and in particular the embryonic and iPS cell. PMID:21566712

Hunt, Charles J.

2011-01-01

376

The Effect of Topography on Differentiation Fates of Matrigel-Coated Mouse Embryonic Stem Cells Cultured on PLGA Nanofibrous Scaffolds  

PubMed Central

Due to pluripotency of embryonic stem (ES) cells, these cells are an invaluable in vitro model that investigates the influence of different physical and chemical cues on differentiation/development pathway of specialized cells. We sought the effect of roughness and alignment, as topomorpholocial properties of scaffolds on differentiation of green fluorescent protein-expressing ES (GFP-ES) cells into three germ layers derivates simultaneously. Furthermore, the effect of Matrigel as a natural extracellular matrix in combination with poly(lactic-co-glycolic acid) (PLGA) nanofibrous scaffolds on differentiation of mouse ES cells has been investigated. The PLGA nanofibrous scaffolds with different height and distribution of roughness and alignments were fabricated. Then, the different cell differentiation fats of GFP-ES cells plated on PLGA and PLGA/Matrigel scaffolds were analyzed by gene expression profiling. The findings demonstrated that distinct ranges of roughness, height, and distribution can support/promote a specific cell differentiation fate on scaffolds. Coating of scaffolds with Matrigel has a synergistic effect in differentiation of mesoderm-derived cells and germ cells from ES cells, whereas it inhibits the derivation of endodermal cell lineages. It was concluded that the topomorpholocial cues such as roughness and alignment should be considered in addition to other scaffolds properties to design an efficient electrospun scaffold for specific tissue engineering. PMID:21981309

Abasi, Mozhgan; Babaloo, Hamideh; Terraf, Panieh; Safi, Mojtaba; Saeed, Mahdi; Barzin, Jalal; Zandi, Mojgan; Soleimani, Masoud

2012-01-01

377

Effective surface-based cryopreservation of human embryonic stem cells by vitrification.  

PubMed

Human embryonic stem cells (hESCs) are candidates for many applications in the areas of regenerative medicine, tissue engineering, basic scientific research as well as pharmacology and toxicology. However, use of hESCs is limited by their sensitivity to freezing and thawing procedures. Hence, this emerging science needs new, reliable preservation methods for the long-term storage of large quantities of functional hESCs remaining pluripotent after post-thawing and culturing. Here, we present a highly efficient, surface based vitrification method for the cryopreservation of large numbers of adherent hESC colonies, using modified cell culture substrates. This technique results in much better post-thaw survival rate compared to cryopreservation in suspension and allows a quick and precise handling and storage of the cells, indicating low differentiation rates. PMID:21910982

Beier, A F J; Schulz, J C; Dörr, D; Katsen-Globa, A; Sachinidis, A; Hescheler, J; Zimmermann, H

2011-12-01

378

A comparison study in the proteomic signatures of multipotent germline stem cells, embryonic stem cells, and germline stem cells  

Microsoft Academic Search

Germline stem (GS) cells can only differentiate into germline cells, while multipotent germ stem (mGS) cells, like embryonic stem (ES) cells, can differentiate into various somatic cells and tissues. The proteomic profiles in GS and mGS cells were compared by two-dimensional gel electrophoresis. Ten down-regulated and 16 up-regulated proteins were differentially expressed in mGS cells in comparison to GS cells,

Hajime Kurosaki; Yasuhiro Kazuki; Masaharu Hiratsuka; Toshiaki Inoue; Yasuhisa Matsui; Chi Chiu Wang; Mito Kanatsu-Shinohara; Takashi Shinohara; Tosifusa Toda; Mitsuo Oshimura

2007-01-01

379

Enhanced photodynamic therapy and effective elimination of cancer stem cells using surfactant-polymer nanoparticles.  

PubMed

Photodynamic therapy is a potentially curative treatment for various types of cancer. It involves energy transfer from an excited photosensitizer to surrounding oxygen molecules to produce cytotoxic singlet oxygen species, a process termed as type II reaction. The efficiency of photodynamic therapy is greatly reduced because of the reduced levels of oxygen, often found in tumor microenvironments that also house cancer stem cells, a subpopulation of tumor cells that are characterized by enhanced tumorigenicity and resistance to conventional therapies. We show here that encapsulation of a photosensitizer, methylene blue, in alginate-Aerosol OT nanoparticles leads to an increased production of reactive oxygen species (ROS) under both normoxic and hypoxic conditions. ROS generation was found to depend on the interaction of the cationic photosensitizer with the anionic alginate polymer. Dye-polymer interaction was characterized by formation of methylene blue dimers, potentially enabling electron transfer and a type I photochemical reaction that is less sensitive to environmental oxygen concentration. We also find that nanoparticle encapsulated methylene blue has the capacity to eliminate cancer stem cells under hypoxic conditions, an important goal of current cancer therapy. PMID:25061685

Usacheva, Marina; Swaminathan, Suresh Kumar; Kirtane, Ameya R; Panyam, Jayanth

2014-09-01

380

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

E-print Network

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

Lin, Sabrina Chia-Chin

2010-01-01

381

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

E-print Network

Embryonic Stem Cells (hESCs) 0.05% trypsin/EDTA solution.stem  cells  were  cultured  in  suspension   vii   with  cigarette  smoke  solutions  stem cells were collected, centrifuged, resuspended in fresh medium without smoke solution,

Lin, Sabrina Chia-Chin

2010-01-01

382

Science: Embryos and Stem Cells  

NSDL National Science Digital Library

It's quite easy to stay abreast of all the developments within the world of embryos and stem cell research with this handy site created and maintained by staff members at the Guardian newspaper. On their page, visitors can read news reports from the frontlines of scientific research in these areas, and also check out the latest posts from the weblogs they maintain on these matters. Further down the page, visitors will find a selection of specialized reports on both stem cell research and the manipulation and transformation of embryos. Visitors can also sign up to receive an RSS feed and even learn about related subjects, including genetics and biotechnology.

2008-06-04

383

Notions about human stem cells. [Stem cell proliferation  

Microsoft Academic Search

Precise characterization of the structure of hemopoiesis in man and its quantitation is required for an understanding of hemopoietic regulation and its response to toxic agents, during and after chemotherapy and radiotherapy, in the course of various diseases, and in individuals exposed to agents known to be or which may be toxic to the bone marrow. Knowledge of stem cell

E. P. Cronkite; L. E. Feinendegen

1975-01-01

384

Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Strontium ranelate (SrR) inhibits proliferation of BMMSCs. Black-Right-Pointing-Pointer SrR increases osteoblastic but decreases adipocytic differentiation of BMMSCs. Black-Right-Pointing-Pointer SrR increases expression of Runx2, BSP and OCN by BMMSCs in osteogenic medium. Black-Right-Pointing-Pointer SrR decreases expression of PPAR{gamma}, aP2/ALBP and LPL by BMMSCs in adipogenic medium. -- Abstract: Strontium ranelate (SrR) was an effective anti-osteoporotic drug to increase bone formation and decrease bone resorption. However, reports about the effect of SR on osteoblastic and adipocytic differentiation from bone marrow mesenchymal stem cells (BMMSCs) are limited. The purpose of this study is to evaluate whether SrR affects the ability of BMMSCs to differentiate into osteoblasts or adipocytes. Rat BMMSCs were identified by flow cytometry and exposed to SR (0.1 and 1.0 mM Sr{sup 2+}) under osteogenic or adipogenic medium for 1 and 2 weeks. The proliferation and differentiation of BMMSCs were analyzed by MTT, alkaline phosphatase (ALP), Oil red O staining, quantitative real-time RT-PCR and Western blot assays. SrR significantly inhibited the proliferation, increased osteoblastic but decreased adipocytic differentiation of rat BMMSCs dose-dependently. In osteogenic medium, SrR increased the expression of ALP, the mRNA levels of Cbfa1/Runx2, bone sialoprotein, and osteocalcin by RT-PCR, and the protein levels of Cbfa1/Runx2 by Western blot. In adipogenic medium, SrR decreased the mRNA levels of PPAR{gamma}2, adipocyte lipid-binding protein 2 (aP2/ALBP), and lipoprotein lipase (LPL) by RT-PCR, and the protein expression of PPAR{gamma} in Western blot analysis. These results indicated that the effects of SrR to promote osteoblastic but inhibit adipocytic differentiation of BMMSCs might contribute to its effect on osteoporosis treatment.

Li, Yunfeng; Li, Jihua; Zhu, Songsong; Luo, En; Feng, Ge; Chen, Qianming [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China)] [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China); Hu, Jing, E-mail: drhu@vip.sohu.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China)] [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Southern Renmin Road, Chengdu 610041 (China)

2012-02-24

385

Epithelial stem cells in teeth  

Microsoft Academic Search

Many tissues and organs maintain a process known as homeostasis, in which cells are replenished as they die as a result of\\u000a apoptosis or injury. The continuously growing mouse incisors are an excellent model for studying the molecular mechanisms\\u000a of cell homeostasis, renewal, and repair. We elucidated these mechanisms in mouse incisors by detecting adult stem cells and\\u000a analyzing the

H. Harada; T. Mitsuyasu; T. Toyono; K. Toyoshima

2002-01-01

386

The Effect of In Vivo Mobilization of Bone Marrow Stem Cells on the Pancreas of Diabetic Albino Rats (A Histological & Immunohistochemical Study)  

PubMed Central

Background and Objectives The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats. Methods and Results Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment. Conclusions This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus. PMID:24298369

Ismail, Zeinab Mohamed Kamel; Kamel, Ashraf Mahmoud Fawzy; Yacoub, Mira Farouk Youssef; Aboulkhair, Alshaymaa Gamal

2013-01-01

387

Head and Neck Cancer Stem Cells  

Microsoft Academic Search

Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of

S. Krishnamurthy; J. E. Nör

2012-01-01

388

Generalized Potential of Adult Neural Stem Cells  

Microsoft Academic Search

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

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

2000-01-01

389

*Institute for Stem Cell Research, GSF --National  

E-print Network

*Institute for Stem Cell Research, GSF -- National Research Center for Environment and Health neural stem cells. THE CELL BIOLOGY OF NEUROGENESIS Magdalena Götz* and Wieland B. Huttner Abstract