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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

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

E-print Network

healing · CXCR4 · Bone morphogenic protein 2 · Stem cell niche ABSTRACT Mesenchymal stem cells (MSC) have- and dose-dependent and, it is exclusively CXCR4-dependent. MSC improved the fracture healing affecting

Miga, Michael I.

3

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

4

Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior  

NASA Astrophysics Data System (ADS)

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

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

2005-08-01

5

Inducing Effects of Zhichan Soup on Neuron Stem Cell Differentiation  

Microsoft Academic Search

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

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

2009-01-01

6

Stress and stem cells  

PubMed Central

The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress. PMID:23799624

Tower, John

2013-01-01

7

Stem Cells  

Microsoft Academic Search

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

Manuela Monti; Carlo Alberto Redi

8

Stem cells, cancer, and cancer stem cells  

Microsoft Academic Search

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

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

2001-01-01

9

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, Mnica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

2013-01-01

10

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 ...

11

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 patients 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 donorrecipient 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

12

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

13

Stem Cells and Diseases  

MedlinePLUS

... U.S. policy? More FAQs Links to related resources Stem Cell Research Center for Regenerative Medicine NIH Stem Cell Unit ... Help My Medical Condition? The International Society for Stem Cell Research (ISSCR) ISSCR has developed information to help you ...

14

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

15

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

16

Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells  

Microsoft Academic Search

Recent evidence suggests that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are resistant to current anticancer therapies. Hence, novel cancer therapies will need to be tested for both tumor regression and CSC targeting. Herein we show that oncolytic reovirus that induces regression of human breast cancer primary tumor samples

Paola Marcato; Cheryl A Dean; Carman A Giacomantonio; Patrick WK Lee

2009-01-01

17

[Antiproliferative and cytotoxic effects of different type cytostatics on mouse pluripotent stem and teratocarcinoma cells].  

PubMed

Pluripotent stem cells are able to proliferate indefinitely and differentiate in vitro into various cell types. However, in most cases in vitro differentiation of the pluripotent stem cells is asynchronous and incomplete, and the residual undifferentiated cells can initiate teratoma development after transplantation into recipients. These features of the pluripotent stem cells are the major issue for development of safe cell therapy technologies based on pluripotent stem cells. Considering significant resemblance of growth rates of pluripotent stem and cancer cells we investigated antiproliferative and cytotoxic effects of different type cytostatics (mitomycin C, etoposide, vinblastine and cycloheximide) on the undifferentiated and differentiating mouse embryonic stem cells, embryonic germ cells, blastocyst and on mouse embryonal teratocarcinoma cells and mouse embryonic fibroblasts. The findings showed that all cytostatics used induced both antiproliferative effects and acute toxic processes in undifferentiated pluripotent stem cells and embryonal teratocarcinoma cells whereas these effects were less in differentiating embryonic stem cells and embryonic fibroblast. Moreover, the trophoblast cells of mouse blastocysts were less sensitive to damaging effects of cytostatics than inner cell mass cells. The examination of deferred effects ofcytostatics revealed that the effects ofmitomycin C, etoposide and vinblastine, but not cycloheximide, were irreversible because survived cells were not able to proliferate. Nevertheless, the numbers of embryonic fibroblasts exposed to etoposide or vinblastine remained unchanged while vast majority of undifferentiated pluripotent cells treated underwent apoptosis. Thus, diverse effects of etoposide and vinblastine on the undifferentiated pluripotent stem cells and differentiated embryonic cells allow us to consider these cytostatics and their analogs as drug-candidates for selective elimination of the residual undifferentiated pluripotent stem cells from population of differentiating cells. These findings demonstrate for the first time the possibility of selective elimination of undifferentiated pluripotent stem cells using cytostatic drugs approved for clinic practice. However, to improve effectiveness and safety of this approach and to prevent mutagenic, carcinogenic and teratogenic effects on undifferentiated pluripotent stem cells and their differentiated cell derivatives large-scale studies ofcytostatic effects using different experimental design and active doses must be performed. PMID:23035583

Gordeeva, O F

2012-01-01

18

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

19

Hematopoietic stem cell donation.  

PubMed

Allogeneic hematopoietic stem cell transplantation is now an important treatment for numerous diseases. Donation of hematopoietic stem cells, either through bone marrow (BM) harvesting or peripheral blood stem cell (PBSC) collection, is a well-established and generally accepted procedure. The BM is aspirated from the posterior iliac crest under spinal or general anesthesia, and common side effects include fatigue and local pain. PBSC collection requires 4-6days of G-CSF injections and leukapheresis 1-2 times. Common side effects of these procedures include bone pain, fatigue, and headache. The side effects of BM and PBSC collections are mostly transient and well tolerated. Severe adverse events are uncommon in healthy donors. At present, there is no definitive evidence to show that the stem cell donation increases the risk of marrow failure or cancer development. Nevertheless, all donors must be carefully evaluated and fully informed before donation. Donors must be able to provide informed consent without being coerced or pressured. Donors and graft products must be examined for potential agents to avoid transmitting infections and other diseases that may jeopardize donor's health during stem cell collection or recipient's well being after transplantation. Understanding the potential physical and psychological complications of stem cell donation and factors that may increase risks is very important to ensure that transplantation physicians maintain positive attitude in conducting this benevolent practice. PMID:23420184

Chen, Shu-Huey; Wang, Tso-Fu; Yang, Kuo-Liang

2013-04-01

20

Effect of midazolam on the proliferation of neural stem cells isolated from rat hippocampus?  

PubMed Central

In many recent studies, the inhibitory transmitter gamma-aminobutyric acid has been shown to modulate the proliferation, differentiation and survival of neural stem cells. Most general anesthetics are partial or allosteric gamma-aminobutyric acid A receptor agonists, suggesting that general anesthetics could alter the behavior of neural stem cells. The neuroprotective efficacy of general anesthetics has been recognized for decades, but their effects on the proliferation of neural stem cells have received little attention. This study investigated the potential effect of midazolam, an extensively used general anesthetic and allosteric gamma-aminobutyric acid A receptor agonist, on the proliferation of neural stem cells in vitro and preliminarily explored the underlying mechanism. The proliferation of neural stem cells was tested using both Cell Counting Kit 8 and bromodeoxyuridine incorporation experiments. Cell distribution analysis was performed to describe changes in the cell cycle distribution in response to midazolam. Calcium imaging was employed to explore the molecular signaling pathways activated by midazolam. Midazolam (3090 ?M) decreased the proliferation of neural stem cells in vitro. Pretreatment with the gamma-aminobutyric acid A receptor antagonist bicuculline or Na-K-2Cl cotransport inhibitor furosemide partially rescued this inhibition. In addition, midazolam triggered a calcium influx into neural stem cells. The suppressive effect of midazolam on the proliferation of neural stem cells can be partly attributed to the activation of gamma-aminobutyric acid A receptor. The calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.

Zhao, Sanjun; Zhu, Yajing; Xue, Rui; Li, Yunfeng; Lu, Hui; Mi, Weidong

2012-01-01

21

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

PubMed

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

22

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

PubMed

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

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

2013-04-15

23

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

24

Effect of silver nanoparticles on human mesenchymal stem cell differentiation  

PubMed Central

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

Diendorf, Jrg; Epple, Matthias; Schildhauer, Thomas A; Kller, Manfred

2014-01-01

25

[Stem cells and cancer].  

PubMed

Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Cancer stem cells are a subpopulation of the cells that form the tumor. The discovery of these human cancer cells opens a perspective for understanding tumor recurrence, drug resistance and metastasis; and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Therapeutic alternatives emerge from a better understanding of the biology and the environment of tumor stem cells. The present paper aims to summarize the characteristics and properties of cancer stem cells, the ongoing research, as well as the best strategies for prevention and control of the mechanisms of tumor recurrence. PMID:25558756

Arvelo, Francisco; Cotte, Carlos; Sojo, Felipe

2014-12-01

26

Characterization and spinal fusion effect of rabbit mesenchymal stem cells  

PubMed Central

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

2013-01-01

27

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

PubMed

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

Do?an, Ay?egl; Yalva, Mehmet Emir; Y?lmaz, Aysu; Rizvanov, Albert; Sahin, Fikrettin

2013-12-01

28

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

29

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

NASA Astrophysics Data System (ADS)

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

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

2013-03-01

30

Cell Stem Cell Dietary and Metabolic Control  

E-print Network

Cell Stem Cell Review Dietary and Metabolic Control of Stem Cell Function in Physiology and Cancer cell function, and cancer initiation are interconnected. Here we will explore the emerging effects cells may respond to shifts in organismal physiology to orchestrate tissue remodeling and some cancers

Sabatini, David M.

31

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.

32

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

PubMed

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

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

2012-08-01

33

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

34

Cell Stem Cell Molecular Analysis of Stem Cells and Their  

E-print Network

homeostasis and regeneration, but also the utility of studies in planarians to broadly inform stem cellCell Stem Cell Article Molecular Analysis of Stem Cells and Their Descendants during Cell Turnover@neuro.utah.edu DOI 10.1016/j.stem.2008.07.002 SUMMARY In adult planarians, the replacement of cells lost

Alvarado, Alejandro Sánchez

35

Hematopoietic Stem Cell Transplantation  

Microsoft Academic Search

\\u000a The purpose of hematopoietic stem cell transplantation (HSCT) is to replace diseased, damaged, or absent hematopoietic stem\\u000a cells (HSCs) with healthy HSCs. In general, allogeneic transplants are used when the hematopoietic stem cells are diseased\\u000a (e.g., leukemia), damaged (e.g., sickle cell disease), or absent (e.g., severe immunodeficiency disease). Autologous transplants\\u000a are used to provide stem cell rescue after higher doses

Robbie Norville; Deborah Tomlinson

36

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

E-print Network

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

Schladow, S. Geoffrey

37

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

38

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

PubMed

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

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

2007-11-01

39

Embryonic stem cells. Stem cell programs.  

PubMed

The availability of human embryonic stem cell lines provides an important tool for scientists to explore the fundamental mechanisms that regulate differentiation into specific cell types. When more is known about the mechanisms that govern these processes, human embryonic stem cells may be clinically useful in generating cell types that have been damaged or depleted by a variety of human diseases. The NIH is actively pursuing a variety of initiatives to promote this developing research field, while continuing and expanding its long-standing investment in adult stem cells and research. PMID:12738840

Zerhouni, Elias

2003-05-01

40

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

PubMed Central

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

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

2015-01-01

41

Graphene based scaffolds effects on stem cells commitment.  

PubMed

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

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

2014-10-25

42

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.

43

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

44

Stem Cell Basics  

MedlinePLUS

... U.S. policy? More FAQs Links to related resources Stem Cell Research Center for Regenerative Medicine NIH Stem Cell Unit ... of scientific research, and the potential use of stem cells in research and in treating disease. The primer includes information ...

45

Understanding Embryonic Stem Cells  

NSDL National Science Digital Library

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

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

2008-04-10

46

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

47

Stemming vision loss with stem cells.  

PubMed

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

2010-09-01

48

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

49

Effect of isolation methodology on stem cell properties and multilineage differentiation potential of human dental pulp stem cells.  

PubMed

Dental pulp stem cells (DPSCs) are an attractive alternative mesenchymal stem cell (MSC) source because of their isolation simplicity compared with the more invasive methods associated with harvesting other MSC sources. However, the isolation method to be favored for obtaining DPSC cultures remains under discussion. This study compares the stem cell properties and multilineage differentiation potential of DPSCs obtained by the two most widely adapted isolation procedures. DPSCs were isolated either by enzymatic digestion of the pulp tissue (DPSC-EZ) or by the explant method (DPSC-OG), while keeping the culture media constant throughout all experiments and in both isolation methods. Assessment of the stem cell properties of DPSC-EZ and DPSC-OG showed no significant differences between the two groups with regard to proliferation rate and colony formation. Phenotype analysis indicated that DPSC-EZ and DPSC-OG were positive for CD29, CD44, CD90, CD105, CD117 and CD146 expression without any significant differences. The multilineage differentiation potential of both stem cell types was confirmed by using standard immuno(histo/cyto)chemical staining together with an in-depth ultrastructural analysis by means of transmission electron microscopy. Our results indicate that both DPSC-EZ and DPSC-OG could be successfully differentiated into adipogenic, chrondrogenic and osteogenic cell types, although the adipogenic differentiation of both stem cell populations was incomplete. The data suggest that both the enzymatic digestion and outgrowth method can be applied to obtain a suitable autologous DPSC resource for tissue replacement therapies of both bone and cartilage. PMID:23715720

Hilkens, P; Gervois, P; Fanton, Y; Vanormelingen, J; Martens, W; Struys, T; Politis, C; Lambrichts, I; Bronckaers, A

2013-07-01

50

The effects of histone deacetylase inhibitors on glioblastoma-derived stem cells.  

PubMed

Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited effective treatment options. Cancer stem cells (CSCs), a subpopulation of cancer cells with stem cell properties found in GBMs, have been shown to be extremely resistant to radiation and chemotherapeutic agents and have the ability to readily reform tumors. Therefore, the development of therapeutic agents targeting CSCs is extremely important. In this study, we isolated glioblastoma-derived stem cells (GDSCs) from GBM tissue removed from patients during surgery and analyzed their gene expression using quantitative real-time PCR and immunocytochemistry. We examined the effects of histone deacetylase inhibitors trichostatin A (TSA) and valproic acid (VPA) on the proliferation and gene expression profiles of GDSCs. The GDSCs expressed significantly higher levels of both neural and embryonic stem cell markers compared to GBM cells expanded in conventional monolayer cultures. Treatment of GDSCs with histone deacetylase inhibitors, TSA and VPA, significantly reduced proliferation rates of the cells and expression of the stem cell markers, indicating differentiation of the cells. Since differentiation into GBM makes them susceptible to the conventional cancer treatments, we posit that use of histone deacetylase inhibitors may increase efficacy of the conventional cancer treatments for eliminating GDSCs. PMID:24874578

Alvarez, Angel A; Field, Melvin; Bushnev, Sergey; Longo, Matthew S; Sugaya, Kiminobu

2015-01-01

51

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

PubMed

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

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

2012-07-01

52

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

53

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.

Irwin Slesnick

2004-01-01

54

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

PubMed Central

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

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

2013-01-01

55

Cell chip to detect effects of graphene oxide nanopellet on human neural stem cell.  

PubMed

The graphene oxide (GO) nanopellet, a potentially useful carbon-based material, recently started being applied in cell-based research areas. Its toxicity assessment using the neural-stem-cell-based chip has not been thoroughly reported yet, though. Herein, a cell chip was fabricated to electrochemically detect the toxic effects of GO nanopellets on HBl.F3 cells. The RGD peptide was immobilized on the gold electrode surface to enhance the binding affinity of the HBl.F3 cells to the electrode surface. A clear redox peak appeared when the HB1.F3 cells were analyzed via cyclic voltammetry. The GO nanopellet was analyzed via Raman spectroscopy to confirm its distinct structural characteristics that normally differ from those of graphite oxide. After GO was added to the HB1.F3 cells, differential pulse voltammetry was performed to discover the toxic effects of GO nanopellets on HB1.F3 cells. A negative correlation was achieved between the concentration of the GO nanopellets and the cell viability, which was verified via both MTT assay and a microscopic imaging tool. Thus, these electrochemical tools can be usefully applied to the toxicity assessment of various kinds of carbon-based materials. PMID:22966543

Kang, Se-Mi; Kim, Tae-Hyung; Choi, Jeong-Woo

2012-07-01

56

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

57

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

Microsoft Academic Search

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

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

2005-01-01

58

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; Danils, Annick; De Wever, Olivier; Bracke, Marc; Hendrikx, Marc; Hensen, Karen; Rummens, Jean-Luc

2014-01-01

59

Engineering stem cell niches in bioreactors  

PubMed Central

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

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

2013-01-01

60

Cell Stem Cell Clinical Progress  

E-print Network

, 2009), low cell numbers in single UCB units have limited the suitability of UCB transplan- tationCell Stem Cell Clinical Progress Rapid Expansion of Human Hematopoietic Stem Cells by Automated, Toronto, ON M5S 3E1, Canada 4Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins

Zandstra, Peter W.

61

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

SciTech Connect

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

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

2008-09-12

62

Embryonic Stem Cell Course  

NSDL National Science Digital Library

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

63

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 in situ tracheal regeneration: the bionic tissue engineered transplantation approach. J Cell Mol Med. Jul

Schüler, Axel

64

Effects of hyperthermia and radiation on mouse testis stem cells  

SciTech Connect

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

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

1981-11-01

65

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.

66

Induced neural stem cells have protective effects on cortical neuronal cells in vitro.  

PubMed

Reprogramming of fibroblasts into induced neural stem cells (NSCs) is a potentially unlimited source of neurons. In this study, we cocultured cortical neuronal cells with iNSCs in a transwell system. We then investigated the effects of coculture on apoptosis and the secretion of cytokines and growth factors. Compared with the cultured cortical neuronal culture alone, cortical neuronal cells cocultured with iNSCs exhibited increased proliferation. TUNEL assay was used to assess the rate of apoptosis at selected time intervals (24, 48 and 72h). Cells cocultured with iNSCs had fewer apoptotic cells than those cultured without iNSCs. When TUNEL assay was performed in parallel with staining for the neuronal marker Tuj1, the number of neuronal apoptotic cells was found to be lower in cells cocultured with iNSCs than in those cultured without iNSCs for 72h. Secretion of cytokines and growth factors by iNSCs was evaluated by ELISA. Compared to cells cultured without iNSCs, coculture decreased levels of the inflammatory cytokines and increased levels of HGF and VEGF. These findings indicated that iNSCs could be used as a new treatment strategy for neurodegenerative conditions by promoting proliferation and decreasing apoptosis of cortical neuronal cells. PMID:25410028

Kim, Jin Hee; Sun, Woong; Han, Dong Wook; Lim, Dong-Jun; Lee, Jangbo

2014-11-20

67

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

PubMed

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

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

2013-12-01

68

Stem cell therapy without the cells.  

PubMed

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 cells(1) 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

2013-11-01

69

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

70

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

71

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

PubMed

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

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

2013-05-01

72

Cell Stem Cell Short Article  

E-print Network

Cell Stem Cell Short Article High Mitochondrial Priming Sensitizes hESCs to DNA of Pediatric Newborn Medicine 4Department of Medicine, Division of Genetics Brigham & Women's Hospital, BostonDivision of Newborn Medicine, Boston Children's Hospital, Boston, MA 02115, USA 7Harvard Stem Cell

Lahav, Galit

73

Effects of Biologic Scaffolds on Human Stem Cells and Implications for CNS Tissue Engineering  

PubMed Central

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.

2014-01-01

74

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

E-print Network

The effect of mesenchymal stem cell shape on the maintenance of multipotency Douglas Zhang multipotency after prolonged passaging. Cell culture conditions that promote maintenance of multipotency during 2012 Accepted 10 February 2013 Available online 6 March 2013 Keywords: Mesenchymal stem cells

Kilian, Kristopher A.

75

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

PubMed Central

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

Schmidt, Ray C.; Healy, Kevin E.

2013-01-01

76

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

77

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 cells effects on radiation-induced enteric injury. MSCs from ?-Gal-transgenic mice were transplanted into C57BL\\/6J\\u000a recipient mice that received abdominal irradiation (13Gy). 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

78

Stem Cell Differentiation Game  

NSDL National Science Digital Library

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

Mary Colvard

2010-01-01

79

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

PubMed

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

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

2014-12-01

80

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

81

The effect of mineral coating morphology on mesenchymal stem cell attachment and expansion  

PubMed Central

Previous studies have demonstrated the influence of calcium phosphate (CaP) mineral coating characteristics on cell attachment, proliferation, and differentiation. However, the wide range of mineral properties that can potentially influence cell behavior calls for an efficient platform to screen for the effects of specific mineral properties. To address this need, we have developed an efficient well-plate format to probe for the effects of mineral coating properties on stem cell behavior. Specifically, here we systematically controlled mineral coating morphology by modulating ion concentrations in modified simulated body fluids (mSBF) during mineral nucleation and growth. We found that mineral micro-morphology could be gradually changed from spherulitic, to plate-like, to net-like depending on [Ca2+] and [PO43?] in mSBF solutions, while other mineral properties (Ca/P ratio, crystallinity, dissolution rate) remained constant. Differences in mineral morphology resulted in significant differences in stem cell attachment and expansion in vitro. These findings suggest that an enhanced throughput mineral coating format may be useful to identify mineral coating properties for optimal stem cell attachment and expansion, which may ultimately permit efficient intraoperative seeding of patient derived stem cells.

Choi, Siyoung

2015-01-01

82

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; OHara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathlia L. M.; Anderson, Richard A.; Sharpe, Richard M.

2014-01-01

83

Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study  

PubMed Central

Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-? (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-? following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury. PMID:23936322

Moodley, Yuben; Vaghjiani, Vijesh; Chan, James; Baltic, Svetlana; Ryan, Marisa; Tchongue, Jorge; Samuel, Chrishan S.; Murthi, Padma; Parolini, Ornella; Manuelpillai, Ursula

2013-01-01

84

Effects of tachyplesinI on human U251 glioma stem cells.  

PubMed

Glioblastoma, is one of the most malignant types of intracranial tumor with complex progressive cellular and underlying molecular events. The use of glioma stem cells (GSCs) offers a promising strategy for tumor therapy in the future. TachyplesinI has been demonstrated to have potential anticancer activity and was first observed in leukocytes. In the present study, the GSC subset was isolated from U251 glioma cells and tachyplesinI was assessed for antitumor activity. As a result, the U251 cells exhibited certain GSC phenotypes, including the expression of stem cell biomarkers CD133 and nestin, when transferred into stem cell culture conditions. The GSCs were grown in an adherent manner in a medium containing serum, while the U251 glioma cells were suspended and cultured in serum?free medium. TachyplesinI damaged the structure of GSC and inhibited the culture of GSC spheres in a time and dose?dependent manner. When tachyplesinI was administered at a concentration of 10?40g/ml, GSC differentiation was induced. GSCs treated with a low dose of tachyplesinI disrupted the plasma membrane and led to a loss of cytoplasmic organelles. These findings indicated that tachyplesinI had an effect on inhibiting tumor stem cells and demonstrated that tachyplesinI inhibited GSCs by disrupting the plasma membranes and inducing GSC differentiation. PMID:25434611

Ding, Hong; Jin, Gang; Zhang, Lijun; Dai, Jianguo; Dang, Jianzhang; Han, Yali

2015-04-01

85

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

PubMed Central

Background Amniotic-fluid-derived stem cells and amniocytes have recently been determined to have wound healing effects, but their mechanism is not yet clearly understood. In this study, the effects of amniotic fluid stem cells and amniocytes on wound healing were investigated through animal experiments. Methods On the back of Sprague-Dawley rats, four circular full-thickness skin wounds 2 cm in diameter were created. The wounds were classified into the following four types: a control group using Tegaderm disc wound dressings and experimental groups using collagen discs, amniotic fluid stem cell discs, and amniocyte discs. The wounds were assessed through macroscopic histological examination and immunohistochemistry over a period of time. Results The amniotic fluid stem cell and amniocyte groups showed higher wound healing rates compared with the control group; histologically, the inflammatory cell invasion disappeared more quickly in these groups, and there was more significant angiogenesis. In particular, these groups had significant promotion of epithelial cell reproduction, collagen fiber formation, and angiogenesis during the initial 10 days of the wound healing process. The potency of transforming growth factor-? and fibronectin in the experimental group was much greater than that in the control group in the early stage of the wound healing process. In later stages, however, no significant difference was observed. Conclusions The amniotic fluid stem cells and amniocytes were confirmed to have accelerated the inflammatory stage to contribute to an enhanced cure rate and shortened wound healing period. Therefore, they hold promise as wound treatment agents. PMID:24086800

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

2013-01-01

86

.Effect of Stem Cell Factor on Colony Growth From Acquired and Constitutional (Fanconi) Aplastic Anemia  

Microsoft Academic Search

The aim of this study was to evaluate the effect of stem cell factor (SCF) on the in vitro growth of bone marrow hemato- poietic progenitors from patients with acquired severe aplas- tic anemia (AA) or Fanconi's anemia (FA). For this purpose, we studied 11 patients with acquired AA (5 at diagnosis, 6 after ALG treatment), 12 patients with FA,

G. P. Bagnara; P. Strippoli; L. Bonsi; M. F. Brizzi; G. C. Avanzi; F. Timeus; G. Piaggio; J. Tong; M. Podesta; G. Paolucci; L. Pegoraro; V. Gabutti; A. Bacigalupo

1992-01-01

87

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

E-print Network

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

Cai, Long

88

Leading Edge Stem Cell Trafficking in Tissue  

E-print Network

that achieving targeted trafficking of stem cells will be critical for effective tissue regeneration fromLeading Edge Review Stem Cell Trafficking in Tissue Development, Growth, and Disease Diana J. Laird, USA 4Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA 5

von Andrian, Ulrich H.

89

Substrate Modulus Directs Neural Stem Cell Behavior  

Microsoft Academic Search

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

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

2008-01-01

90

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

91

Prostate cancer stem cells  

PubMed Central

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

Lang, SH; Frame, FM; Collins, AT

2009-01-01

92

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

93

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

PubMed

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

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

2015-02-20

94

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

95

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

96

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

PubMed

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

Eir, Noem; Sendon-Lago, Juan; Seoane, Samuel; Bermdez, Mara A; Lamelas, Maria Luz; Garcia-Caballero, Toms; Schneider, Jos; Perez-Fernandez, Roman; Vizoso, Francisco J

2014-11-15

97

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

PubMed Central

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

Seoane, Samuel; Bermdez, Mara A.; Lamelas, Maria Luz; Garcia-Caballero, Toms; Schneider, Jos; Perez-Fernandez, Roman; Vizoso, Francisco J.

2014-01-01

98

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.

99

Prostate cancer stem cells  

PubMed Central

The Cancer Stem Cells (CSCs) hypothesis postulates that a minute subpopulation of cells is accountable for cancer initiation and progression. Unlike the stochastic and clonal evolution models, the CSC theory proposes that tumours are hierarchical and only the rare subset of cells at the top of the 'stemness hierarchy tree are adequately equipped biologically to initiate and drive tumourigenesis. CSCs have been implicated in various solid malignancies including prostate cancer (PCa), where their existence seems to provide an explanation for the failure of tumour eradicating therapies. As CSCs are thought to share many properties with normal stem cells, understanding normal stem cells should shed light on the pathomechanisms of cancer and, importantly, on potential therapeutic interventions. The purpose of this paper is to review the existing data on CSCs in PCa, their putative phenotypic markers, potential role in tumour biology and relevance to therapy. PMID:24578892

Abel, Paul

2011-01-01

100

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

PubMed Central

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

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

2011-01-01

101

The Effects of Space Flight and Microgravity on the Growth and Differentiation of PICM-19 Pig Liver Stem Cells.  

Technology Transfer Automated Retrieval System (TEKTRAN)

In order to answer the question, what effects would microgravity have on the growth, differentiation, and function on liver stem cells, the ARS-PICM-19 pig liver stem cell line was cultured in space aboard space shuttle Endeavor for the 16 days of mission STS-126. The liver is among the few organs ...

102

SMOOTH MUSCLE STEM CELLS  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

103

Stem cell plasticity  

Microsoft Academic Search

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

Uma Lakshmipathy; Catherine Verfaillie

2005-01-01

104

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

105

Stem cells and solid cancers.  

PubMed

Recently, there have been significant advances in our knowledge of stem cells found in tissues that can develop solid tumours. In particular, novel stem cell markers have been identified for the first time identifying multipotential cells: a required characteristic of a stem cell. The scarcity of cancer stem cells has been questioned. Current dogma states that they are rare, but novel research has suggested that this may not be the case. Here, we review the latest literature on stem cells, particularly cancer stem cells within solid tumours. We discuss current thinking on how stem cells develop into cancer stem cells and how they protect themselves from doing so and do they express unique markers that can be used to detect stem cells. We attempt to put into perspective these latest advances in stem cell biology and their potential for cancer therapy. PMID:19499244

McDonald, Stuart A C; Graham, Trevor A; Schier, Stefanie; Wright, Nicholas A; Alison, Malcolm R

2009-07-01

106

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

107

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 ... found here: Human Induced Pluripotent Stem Cells NINDS Stem Cell Research on Campus The Intramural Research Program of NINDS ...

108

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

PubMed Central

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

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

2013-01-01

109

Embryonic Stem Cells Cell Signalling Course  

E-print Network

Embryonic Stem Cells Cell Signalling Course Ceské Budjovice November 2013 #12;Pluripotent (stem;1981 Lines of pluripotent cells were established for the first time from mouse embryo ­ Embryonic Stem Cells (Martin & Evans) Embryonic Stem Cells (ESC) ­ step from cancerous pluripotent cells of teratocarcinomas

South Bohemia, University of

110

Embryonic Stem Cells Cell Signalling Course  

E-print Network

Embryonic Stem Cells Cell Signalling Course Ceské Budjovice January 2013 #12;Pluripotent (stem;1981 Lines of pluripotent cells were established for the first time from mouse embryo ­ Embryonic Stem Cells (Martin & Evans) Embryonic Stem Cells (ESC) ­ step from cancerous pluripotent cells of teratocarcinomas

South Bohemia, University of

111

Melanoma stem cells.  

PubMed

The cancer stem cell concept significantly broadens our understanding of melanoma biology. However, this concept should be regarded as an integral part of a holistic cancer model that also includes the genetic evolution of tumor cells and the variability of cell phenotypes within a dynamic tumor microenvironment. The biologic complexity and methodological difficulties in identifying cancer stem cells and their biomarkers are currently impeding the direct translation of experimental findings into clinical practice. Nevertheless, it is these methodological shortcomings that provide a new perspective on the phenotypic heterogeneity and plasticity of melanoma with important consequences for future therapies. The development of new combination treatment strategies, particularly with regard to overcoming treatment resistance, could significantly benefit from targeted elimination of cell subpopulations with cancer stem cell properties. PMID:25631128

Roesch, Alexander

2015-02-01

112

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

113

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

PubMed Central

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

2013-01-01

114

Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro.  

PubMed

Stem cell-based therapy for myocardial regeneration has reported several functional improvements that are attributed mostly to the paracrine effects stimulating angiogenesis and cell survival. This study was conducted to comparatively evaluate the potential of factors secreted by mesenchymal stem cells (MSCs) in normoxic and hypoxic conditions to promote tissue repair by sustaining endothelial cell (EC) adhesion and proliferation and conferring protection against apoptosis. To this aim, a conditioned medium (CM) was generated from MSCs after 24-h incubation in a serum-free normal or hypoxic environment. MSCs exhibited resistance to hypoxia, which induced increased secretion of vascular endothelial growth factor (VEGF) and decreased levels of other cytokines, including stromal-derived factor-1 (SDF). The CM derived from normal (nMSC-CM) and hypoxic cells (hypMSC-CM) induced similar protective effects on H9c2 cells in hypoxia. Minor differences were noticed in the potential of normal versus hypoxic CM to promote angiogenesis, which were likely connected to SDF? and VEGF levels: the nMSC-CM was more effective in stimulating EC migration, whereas the hypMSC-CM had an enhanced effect on EC adhesion. However, the factors secreted by MSCs in normoxic or hypoxic conditions supported adhesion, but not proliferation, of ECs in vitro, as revealed by impedance-based dynamic assessments. Surprisingly, factors secreted by other stem/progenitor cells, such as endothelial progenitor cells (EPCs), had complementary effects to the MSC-CM. Thus, the EPC-CM, in either a normal or hypoxic environment, supported EC proliferation, but did not sustain EC adhesion. Combined use of the MSC-CM and EPC-CM promoted both EC adhesion and proliferation, suggesting that the local angiogenesis at the site of ischemic injury might be better stimulated by simultaneous releasing of factors secreted by multiple stem/progenitor cell populations. PMID:22947186

Burlacu, Alexandrina; Grigorescu, Gabriela; Rosca, Ana-Maria; Preda, Mihai Bogdan; Simionescu, Maya

2013-02-15

115

Factors Secreted by Mesenchymal Stem Cells and Endothelial Progenitor Cells Have Complementary Effects on Angiogenesis In Vitro  

PubMed Central

Stem cell-based therapy for myocardial regeneration has reported several functional improvements that are attributed mostly to the paracrine effects stimulating angiogenesis and cell survival. This study was conducted to comparatively evaluate the potential of factors secreted by mesenchymal stem cells (MSCs) in normoxic and hypoxic conditions to promote tissue repair by sustaining endothelial cell (EC) adhesion and proliferation and conferring protection against apoptosis. To this aim, a conditioned medium (CM) was generated from MSCs after 24-h incubation in a serum-free normal or hypoxic environment. MSCs exhibited resistance to hypoxia, which induced increased secretion of vascular endothelial growth factor (VEGF) and decreased levels of other cytokines, including stromal-derived factor-1 (SDF). The CM derived from normal (nMSC-CM) and hypoxic cells (hypMSC-CM) induced similar protective effects on H9c2 cells in hypoxia. Minor differences were noticed in the potential of normal versus hypoxic CM to promote angiogenesis, which were likely connected to SDF? and VEGF levels: the nMSC-CM was more effective in stimulating EC migration, whereas the hypMSC-CM had an enhanced effect on EC adhesion. However, the factors secreted by MSCs in normoxic or hypoxic conditions supported adhesion, but not proliferation, of ECs in vitro, as revealed by impedance-based dynamic assessments. Surprisingly, factors secreted by other stem/progenitor cells, such as endothelial progenitor cells (EPCs), had complementary effects to the MSC-CM. Thus, the EPC-CM, in either a normal or hypoxic environment, supported EC proliferation, but did not sustain EC adhesion. Combined use of the MSC-CM and EPC-CM promoted both EC adhesion and proliferation, suggesting that the local angiogenesis at the site of ischemic injury might be better stimulated by simultaneous releasing of factors secreted by multiple stem/progenitor cell populations. PMID:22947186

Grigorescu, Gabriela; Rosca, Ana-Maria; Preda, Mihai Bogdan; Simionescu, Maya

2013-01-01

116

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

PubMed Central

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

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

2013-01-01

117

Effects of growth factors on dental stem/progenitor cells.  

PubMed

The primary goal of regenerative endodontics is to restore the vitality and functions of the dentin-pulp complex, as opposed to filing of the root canal with bioinert materials. A myriad of growth factors regulates multiple cellular functions including migration, proliferation, differentiation, and apoptosis of several cell types intimately involved in dentin-pulp regeneration. Recent work showing that growth factor delivery, without cell transplantation, can yield pulp-dentin-like tissues invivo provides one of the tangible pathways for regenerative endodontics. This review synthesizes knowledge on many growth factors that are known or anticipated to be efficacious in dental pulp-dentin regeneration. PMID:22835538

Kim, Sahng G; Zhou, Jian; Solomon, Charles; Zheng, Ying; Suzuki, Takahiro; Chen, Mo; Song, Songhee; Jiang, Nan; Cho, Shoko; Mao, Jeremy J

2012-07-01

118

Neural stem cell transplantation in a model of fetal alcohol effects  

Microsoft Academic Search

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

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

119

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

120

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.

Catherine Verfaillie

2009-01-23

121

Pleiotropic effects of Prostaglandin E2 in hematopoiesis; Prostaglandin E2 and other eicosanoids regulate hematopoietic stem and progenitor cell function  

PubMed Central

Eicosanoids have been implicated in the physiological regulation of hematopoiesis with pleiotropic effects on hematopoietic stem cells and various classes of lineage restricted progenitor cells. Herein we review the effects of eicosanoids on hematopoiesis, focusing on new findings implicating prostaglandin E2 in enhancing hematopoietic stem cell engraftment by enhancing stem cell homing, survival and self-renewal. We also describe a role for cannabinoids in hematopoiesis. Lastly, we discuss the yin and yang of various eicosanoids in modulating hematopoietic stem and progenitor cell functions and summarize potential strategies to take advantage of these effects for therapeutic benefit for hematopoietic stem cell transplantation. PMID:21722751

Pelus, Louis M.; Hoggatt, Jonathan

2011-01-01

122

Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin.  

PubMed

New theories on the regeneration of ischemic vasculature have emerged indicating a pivotal role of adult stem cells. The aim of this study was to investigate homing and hemodynamic effects of circulating bone marrow-derived mesenchymal stem cells (MSCs) in a critically ischemic murine skin flap model. Bone marrow-derived mesenchymal stem cells (Lin(-)CD105(+)) were harvested from GFP(+)-donor mice and transferred to wildtype C57BL/6 mice. Animals receiving GFP(+)-fibroblasts served as a control group. Laser scanning confocal microscopy and intravital fluorescence microscopy were used for morphological analysis, monitoring and quantitative assessment of the stem cell homing and microhemodynamics over two weeks. Immunohistochemical staining was performed for GFP, eNOS, iNOS, VEGF. Tissue viability was analyzed by TUNEL-assay. We were able to visualize perivascular homing of MSCs in vivo. After 4 days, MSCs aligned along the vascular wall without undergoing endothelial or smooth muscle cell differentiation during the observation period. The gradual increase in arterial vascular resistance observed in the control group was abolished after MSC administration (P<0.01). At capillary level, a strong angiogenic response was found from day 7 onwards. Functional capillary density was raised in the MSC group to 197% compared to 132% in the control group (P<0.01). Paracrine expression of VEGF and iNOS, but not eNOS could be shown in the MSC group but not in the controls. In conclusion, we demonstrated that circulating bone marrow-derived MSCs home to perivascular sites in critically ischemic tissue, exhibits paracrine function and augment microhemodynamics. These effects were mediated through arteriogenesis and angiogenesis, which contributed to vascular regeneration. PMID:22391452

Schlosser, Stefan; Dennler, Cyrill; Schweizer, Riccardo; Eberli, Daniel; Stein, Jens V; Enzmann, Volker; Giovanoli, Pietro; Erni, Dominique; Plock, Jan A

2012-05-01

123

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

124

Stem cells and the Planarian Schmidtea mediterranea  

Microsoft Academic Search

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

Alejandro Snchez Alvarado

2007-01-01

125

Fifth Annual Stem Cell Summit.  

PubMed

The Fifth Annual Stem Cell Summit, held in New York, included topics covering new commercial developments in the research field of stem cell-based therapies. This conference report highlights selected presentations on embryonic and adult stem cells, stem cell-based therapies for the treatment of orthopedic and cardiovascular indications and inflammatory diseases, as well as technologies for processing and storing stem cells. Investigational therapies discussed include placental expanded (PLX) cells (Pluristem Therapeutics Inc), StemEx (Gamida-Teva Joint Venture/Teva Pharmaceutical Industries Ltd) and remestemcel-L (Osiris Therapeutics Inc/Genzyme Corp/JCR Pharmaceuticals Co Ltd/ Mochida Pharmaceutical Co Ltd). PMID:20373251

Knowlton, Daniel

2010-04-01

126

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

127

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

PubMed Central

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

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

2012-01-01

128

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 1C/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

129

Interferon-?-secreting mesenchymal stem cells exert potent antitumor effect in vivo.  

PubMed

Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can be isolated easily from bone marrow, adipose tissue, umbilical cord and many other tissues. MSCs have been shown to specifically migrate to inflammatory sites, including tumors, and hold great promise as tumor-specific vectors to deliver antitumor agents. Interferon-? (IFN?) has been used in clinic to treat various types of tumors; however, because of its short half-life, significant therapeutic effects require high doses that often results in serious side effects. Here, we tested whether MSCs continuingly secreting IFN? can exert a persistent antitumor effect and eliminate the side effects associated with high clinical doses of recombinant IFN?. We found that even a small number of IFN?-secreting MSCs could potently halt B16 tumor growth in vivo. The antitumor activity of IFN?-secreting MSCs was largely abolished in immunodeficient mice, an effect largely attributed to natural killer cells and CD8(+) T cells. Therefore, IFN?-secreting MSCs provide an innovative strategy for tumor therapy. PMID:24186200

Xu, C; Lin, L; Cao, G; Chen, Q; Shou, P; Huang, Y; Han, Y; Wang, Y; Shi, Y

2014-10-16

130

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

131

Controversies over stem cell research  

Microsoft Academic Search

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

Gorka Orive; Rosa M. Hernndez; Alicia R. Gascn; Manoli Igartua; Jos Luis Pedraz

2003-01-01

132

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

133

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

134

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

PubMed Central

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

135

Differences between graft product and donor side effects following bone marrow or stem cell donation  

Microsoft Academic Search

We report graft product stem cell yields and donor safety results of a randomized multicenter study comparing allogeneic peripheral blood stem cell (PBSC) PBSC transplantation with BM transplantation. Matched HLA-identical sibling donors (n=329) were randomized to filgrastim-mobilized PBSC or bone marrow (BM) donation groups. Median yields per kg recipient weight of CD34+ cells, T cells, and natural killer (NK) cells,

G Favre; M Beksa; A Bacigalupo; T Ruutu; A Nagler; E Gluckman; N Russell; J Apperley; J Szer; K Bradstock; A Buzyn; J Matcham; A Gratwohl; N Schmitz

2003-01-01

136

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

137

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

PubMed Central

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

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

2013-01-01

138

Stem cells today: B1. Bone marrow stem cells  

Microsoft Academic Search

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

RG Edwards

2004-01-01

139

Cancer stem cell theory and the warburg effect, two sides of the same coin?  

PubMed

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

Pacini, Nicola; Borziani, Fabio

2014-01-01

140

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

PubMed Central

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

Pacini, Nicola; Borziani, Fabio

2014-01-01

141

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.

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 hypoxia on the immunomodulatory properties of human gingiva-derived mesenchymal stem cells.  

PubMed

The environment of bone marrow mesenchymal stem cells (MSCs) is hypoxic, which plays an important role in maintaining their self-renewal potential and undifferentiated state. MSCs have been proven to possess immunomodulatory properties and have been used clinically to treat autoimmune diseases. Here, we tested the effects of hypoxia on the immunomodulatory properties of MSCs and examined its possible underlying mechanisms. We found that hypoxic stimulation promoted the immunomodulatory properties of human gingiva-derived mesenchymal stem cells (hGMSCs) by enhancing the suppressive effects of hGMSCs on peripheral blood mononuclear cells (PBMCs). The proliferation of PBMCs was significantly inhibited, while the apoptosis of PBMCs was increased, which was associated with the Fas ligand (FasL) expression of hGMSCs. The in vivo study showed that systemically infused hGMSCs could enhance skin wound repair, and 24-h hypoxic stimulation significantly promoted the reparative capacity of hGMSCs. For mechanism, hGMSC treatment inhibited the local inflammation of injured skin by suppressing the inflammatory cells, reducing the pro-inflammatory cytokine tumor necrosis factor-? (TNF-?), and increasing anti-inflammatory cytokine interleukin-10 (IL-10), which was promoted by hypoxia. Hypoxia preconditioning may be a good optimizing method to promote the potential of MSCs for the future cell-based therapy. PMID:25403565

Jiang, C M; Liu, J; Zhao, J Y; Xiao, L; An, S; Gou, Y C; Quan, H X; Cheng, Q; Zhang, Y L; He, W; Wang, Y T; Yu, W J; Huang, Y F; Yi, Y T; Chen, Y; Wang, J

2015-01-01

144

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

145

Effects of carbon ion beam on putative colon cancer stem cells and its comparison with X-rays.  

PubMed

Although carbon ion therapy facilities are expensive, the biological effects of carbon ion beam treatment may be better against cancer (and cancer stem cells) than the effects of a photon beam. To investigate whether a carbon ion beam may have a biological advantage over X-rays by targeting cancer stem-like cells, human colon cancer cells were used in vitro and in vivo. The in vitro relative biological effectiveness (RBE) values of a carbon ion beam relative to X-rays at the D10 values were from 1.63 to 1.74. Cancer stem-like CD133(+), CD44(+)/ESA(+) cells had a greater ability for colony and spheroid formation, as well as in vivo tumorigenicity compared with the CD133(-), CD44(-)/ESA(-) cells. FACS (fluorescence-activated cell sorting) data showed that cancer stem-like cells were more highly enriched after irradiation with X-rays than carbon ion at doses that produced the same level of biological efficacy. A colony assay for cancer stem-like cells showed that RBE values calculated by the D10 levels were from 2.05 to 2.28 for the carbon ion beam relative to X-rays. The in vivo xenotransplant assay showed an RBE of 3.05 to 3.25, calculated from the slope of the dose-response curve for tumor growth suppression. Carbon ion irradiation with 15 Gy induced more severe xenograft tumor cell cavitation and fibrosis without significant enhancement of cells with putative cancer stem cell markers, CD133, ESA, and CD44, compared with 30 Gy X-rays, and marker positive cells were significantly decreased following 30 Gy carbon ion irradiation. Taken together, carbon ion beam therapy may have an advantage over photon beam therapy by improved targeting of putative colon cancer stem-like cells. PMID:21454414

Cui, Xing; Oonishi, Kazuhiko; Tsujii, Hirohiko; Yasuda, Takeshi; Matsumoto, Yoshitaka; Furusawa, Yoshiya; Akashi, Makoto; Kamada, Tadashi; Okayasu, Ryuichi

2011-05-15

146

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

PubMed Central

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.

2014-01-01

147

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

148

Stem Cell Interaction with Topography  

Microsoft Academic Search

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

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

149

Oxidants, Metabolism and Stem Cell Biology  

PubMed Central

Adult stem cells persist throughout the lifetime of the organism and may therefore require specific mechanisms to limit the effects of chronic oxidative stress. Recently, several instructive genetic mouse models have demonstrated the unique susceptibility of stem cells to perturbations in metabolic or redox homeostasis. These results have implications not only for stem cell biology but also suggest a mechanistic link between intracellular oxidants and the decline in regenerative function that occurs as a normal consequence of aging. PMID:22041454

Liu, Jie; Cao, Liu; Finkel, Toren

2013-01-01

150

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

151

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 cellcell 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

152

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

153

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

154

Microarrays and Stem Cells  

NSDL National Science Digital Library

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

Colvard, Mary

2010-01-01

155

Hematopoietic stem cell transplantation without  

E-print Network

Hematopoietic stem cell transplantation without irradiation Claudia Waskow1,2, Vikas Madan2, Susanne Bartels2,4, Ce´line Costa2, Rosel Blasig3 & Hans-Reimer Rodewald2 Hematopoietic stem cell (HSC. These obstacles prevent in vivo analysis of histoincompatible mutant stem cells and of HSC functions in non

Cai, Long

156

Stem Cells and Leukaemia  

Microsoft Academic Search

Studies performed at RCRM have shown that hematopoietic and immune systems reconstitution after irradiation depends greatly\\u000a on the functional abilities of the stem cells. Subset analysis and expression of CD34+ antigens on bone marrow and peripheral\\u000a blood cells were studied in Chernobyl accident clean-up workers including patients with leukemia and myelodysplasia and patients\\u000a exposed to the natural levels of irradiation.

Volodymyr Bebeshko; Dimitry Bazyka

157

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

158

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.

159

Cell Stem Cell The Transcriptional Landscape  

E-print Network

Cell Stem Cell Resource The Transcriptional Landscape of Hematopoietic Stem Cell Ontogeny Shannon Stem Cell Institute, Boston, MA 02115, USA 2Department of Hematology, St. Jude Children's Research Cell Transplantation Program and Children's Hospital Boston, Boston, MA 02115, USA 9Dana Farber Cancer

Collins, James J.

160

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

PubMed Central

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

Linero, Itali; Chaparro, Orlando

2014-01-01

161

The healing effect of stem cells loaded in nanofibrous scaffolds on full thickness skin defects.  

PubMed

In this study, we have evaluated the wound-healing effects of unrestricted somatic stem cells loaded in chitosan-cross linked PHBV nanofibrous scaffold, implanted into the full thickness skin defects of rats. Afterwards, the scaffolds were evaluated by structural, microscopic, physical and mechanical assays and cell culture analyses. Defects were treated with the scaffolds without and with USSCs. MTT assay, immunostaining, and wound pathology were performed for groups twenty one days after implantation. SEM images showed the average diameter of about 100 nm for the nanofibrous scaffolds, increasing up to 500 nm after chitosan-crosslinking. Results of physical and mechanical analyses also showed a good resilience and compliance with movement as a skin graft. Cellular experiments showed a better cell adhesion, growth and proliferation inside the cross-linked nanofibrous scaffolds compared to un-cross linked ones. In animal models, all groups, excluding the control group, exhibited the most pronounced effect on wound closure, with the statistically significant improvement in wound healing being seen at post-operative day 21. Histological and immunostaining examinations of healed wounds from all groups, especially the groups treated with stem cells. Thus, the grafting of chitosan-cross-linked nanofibrous scaffold loaded with USSC showed better results during the healing process of skin defects in rat models. PMID:23980496

Biazar, E; Keshel, S Heidari

2013-09-01

162

[Bioethical challenges of stem cell tourism].  

PubMed

Stem cells have drawn extraordinary attention from scientists and the general public due to their potential to generate effective therapies for incurable diseases. At the same time, the production of embryonic stem cells involves a serious ethical issue concerning the destruction of human embryos. Although adult stem cells and induced pluripotential cells do not pose this ethical objection, there are other bioethical challenges common to all types of stem cells related particularly to the clinical use of stem cells. Their clinical use should be based on clinical trials, and in special situations, medical innovation, both of which have particular ethical dimensions. The media has raised unfounded expectations in patients and the public about the real clinical benefits of stem cells. At the same time, the number of unregulated clinics is increasing around the world, making direct offers through Internet of unproven stem cell therapies that attract desperate patients that have not found solutions in standard medicine. This is what is called stem cells tourism. This article reviews this situation, its consequences and the need for international cooperation to establish effective regulations to prevent the exploitation of patients and to endanger the prestige of legitimate stem cell research. PMID:24448860

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

2013-08-01

163

Effect of Endogenous Bone Marrow Derived Stem Cells Induced by AMD-3100 on Expanded Ischemic Flap.  

PubMed

The purpose of this study was to devise an expanded ischemic flap model and to investigate the role of AMD-3100 (Plerixafor, chemokine receptor 4 inhibitor) in this model by confirming its effect on mobilization of stem cells from the bone marrow. Male Sprague-Dawley rats were used as an animal research model. The mobilization of stem cells from the bone marrow was confirmed in the AMD-3100-treated group. The fractions of endothelial progenitor cells (EPC) and the vascular endothelial growth factor receptor (VEGFR) 2+ cells in the peripheral blood were increased in groups treated with AMD-3100. The expression of vascular endothelial growth factor (VEGF) was increased in response to expansion or AMD injection. The expression of stromal cell derived factor (SDF)-1 and VEGFR2 were increased only in unexpanded flap treated with AMD-3100. Treatment with AMD-3100 increased both the number and area of blood vessels. However, there were no statistically significant differences in the survival area or physiologic microcirculation in rats from the other groups. This endogenous neovascularization induced by AMD-3100 may be a result of the increase in both the area and number of vessels, as well as paracrine augmentation of the expression of VEGF and EPCs. However, the presence of a tissue expander under the flap could block the neovascularization between the flap and the recipient regardless of AMD-3100 treatment and expansion. PMID:25473215

Jeong, Hii-Sun; Lee, Hye-Kyung; Tark, Kwan-Chul; Lew, Dae-Hyun; Koh, Yoon-Woo; Kim, Chul-Hoon; Seo, In-Suck

2014-11-01

164

The Therapeutic Effect of Human Adult Stem Cells Derived from Adipose Tissue in Endotoxemic Rat Model  

PubMed Central

Excessive systemic inflammation following sepsis, trauma or burn could lead to multi-organ damage and death. Bone marrow stromal cells (BMSCs), commonly referred to as mesenchymal stem cells (MSCs), has been studied in several immune-associated diseases in human and animal by modulating the inflammatory response. Adipose tissue derived mesenchymal stem cells (ATSCs), which can be obtained more easily, compared with BMSCs, has emerged as an attractive alternative MSCs source for cell therapy. We investigated the therapeutic effects of human ATSCs (hATSCs) in endotoxemic rat model and their capacity to modulate the inflammatory response. Endotoxemia was induced with Lipopolysaccaride intravenously injection (LPS, 10mg/kg). Animals were divided into the following three groups: (1) saline + saline (n=5), (2) LPS + saline (n=5) and (3) LPS + hATSCs (2x106) (n=5). The administration of LPS caused a consistent systemic inflammatory responses, increased concentrations of the pro-inflammatory cytokines that have an important role in sepsis. Treatment of endotoxemia with hATSCs decreased the level of inflammatory cytokines both in serum and in the lung, reduced inflammatory changes in the lung, prevented apoptosis in the kidney and improved multi-organ injury. In conclusion, our data demonstrates that hATSCs regulate the immue/inflammatory responses and improve multi-organ injury and they could be attractive candidates for cell therapy to treat endotoxemia. PMID:23289000

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

2013-01-01

165

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

PubMed

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-nave 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

2014-09-30

166

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-nave 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

167

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

PubMed Central

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

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

2013-01-01

168

Stem cells in gastric cancer  

PubMed Central

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

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

2015-01-01

169

Effect of ?-carotene on cancer cell stemness and differentiation in SK-N-BE(2)C neuroblastoma cells.  

PubMed

Neuroblastoma is a solid tumor often diagnosed in childhood. While there have been intense efforts to develop a treatment for neuroblastoma, current therapies remain unsuccessful due to high rate of resistance and metastasis. Most cancers originate from a subset of self-renewing cells, primarily cancer stem cells (CSCs), which establish a tumor through continuous self-renewal and differentiation. The successful elimination of CSCs is an important goal in the development of effective strategies to achieve complete remission for cancers. Although ?-carotene has been associated with several anticancer mechanisms, the efficacy of ?-carotene against CSCs remains unclear. In the present study, ?-carotene was shown to reduce cell growth and induce neuronal cell differentiation, concomitant with a marked increase in the phosphorylation of extracellular signal-regulated kinases (ERK) (p42/p44). More importantly, ?-carotene inhibited self-renewal characteristics of CSCs and decreased expression of several stem cell markers. Levels of mRNA and protein of Drosophila delta-like 1 homolog (Drosophila) (DLK1) were downregulated following treatment with ?-carotene. In addition, knockdown of DLK1 by siRNA enhanced the inhibitory effect of ?-carotene on colony formation of neuroblastoma cells. ?-carotene also potentiated the effect of cisplatin on the self-renewal characteristics of CSCs in neuroblastoma, revealing that ?-carotene has the capacity to resensitize cells to cisplatin cytotoxicity by directly targeting CSCs. In conclusion, ?-carotene was shown to strongly increase the anticancer efficacy against neuroblastoma cancer stem-like cells. Moreover, these results suggest that the targeting of CSCs is a novel mechanism of ?-carotene. Thus, ?-carotene is a potential chemotherapeutic reagent for this cancer. PMID:23900747

Lee, Hyun Ah; Park, Seolhyun; Kim, Yuri

2013-10-01

170

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 g/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 g/ml, may positively affect cell proliferation and mineralization. The most proliferation and enzyme activity were seen with dose of 5 g/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

171

Effect of Human Whartons Jelly Mesenchymal Stem Cell Paracrine Signaling on Keloid Fibroblasts  

PubMed Central

Keloid scars are abnormal benign fibroproliferative tumors with high recurrence rates and no current efficacious treatment. Accumulating evidence suggests that human umbilical cord Whartons jelly-derived mesenchymal stem cells (WJ-MSCs) have antifibrotic properties. Paracrine signaling is considered one of the main underlying mechanisms behind the therapeutic effects of mesenchymal stem cells. However, the paracrine signaling effects of WJ-MSCs on keloids have not yet been reported. The aim of this study is to investigate paracrine signaling effects of human WJ-MSCs on keloid fibroblasts in vitro. Human umbilical cords and keloid skin samples were obtained, and WJ-MSCs and keloid fibroblasts were isolated and cultured. One-way and two-way paracrine culture systems between both cell types were investigated. Plasminogen activator inhibitor-I and transforming growth factor-?2 (TGF-?2) transcripts were upregulated in keloid fibroblasts cultured with WJ-MSC-conditioned medium (WJ-MSC-CM) and cocultured with inserts, while showing lower TGF-?3 gene expression. Interleukin (IL)-6, IL-8, TGF-?1, and TGF-?2 protein expression was also enhanced. The WJ-MSC-CM-treated keloid fibroblasts showed higher proliferation rates than their control keloid fibroblasts with no significant change in apoptosis rate or migration ability. In our culture conditions, the indirect application of WJ-MSCs on keloid fibroblasts may enhance their profibrotic phenotype. PMID:24436441

Arno, Anna I.; Amini-Nik, Saeid; Blit, Patrick H.; Al-Shehab, Mohammed; Belo, Cassandra; Herer, Elaine

2014-01-01

172

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

173

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

PubMed

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

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

2014-01-01

174

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

PubMed Central

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

Qi, Chen; Xiaofeng, Xu; Xiaoguang, Wang

2014-01-01

175

Normal Stem Cells and Cancer Stem Cells: The Niche Matters  

Microsoft Academic Search

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

Linheng Li; William B. Neaves

176

Stem cells and cancer in the aerodigestive tract.  

PubMed

Recently, there have been significant advances in our knowledge of stem cells found in epithelial tissues. In particular, novel stem cell markers have been identified that for the first time identify multipotential cells; a required characteristic of a stem cell. The scarcity of cancer stem cells has been questioned. Current dogma states that they are rare, but novel research has suggested that this may not be the case. Here I review the latest literature on stem cells, particularly so-called cancer stem cells present in tumours of the respiratory tract and colorectum. I discuss current thinking on how stem cells develop into cancer stem cells, how they protect themselves from doing so, and whether cancer stem cells express unique markers that can be used to detect them. Finally, I attempt to put into perspective these latest advances in cancer stem cell biology from the viewpoint of perhaps more effective cancer therapies. PMID:19775616

Alison, Malcolm R

2009-09-01

177

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; Nr, Jacques E.

2013-01-01

178

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

179

Preconditioning Stem Cells for In Vivo Delivery  

PubMed Central

Abstract Stem cells have emerged as promising tools for the treatment of incurable neural and heart diseases and tissue damage. However, the survival of transplanted stem cells is reported to be low, reducing their therapeutic effects. The major causes of poor survival of stem cells in vivo are linked to anoikis, potential immune rejection, and oxidative damage mediating apoptosis. This review investigates novel methods and potential molecular mechanisms for stem cell preconditioning in vitro to increase their retention after transplantation in damaged tissues. Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to oxidative stress), aggregate formation, and hydrogel encapsulation have been revealed as promising strategies to reduce cell apoptosis in vivo while maintaining biological functions of the cells. Moreover, this review seeks to identify methods of optimizing cell dose preparation to enhance stem cell survival and therapeutic function after transplantation. PMID:25126478

Sart, Sbastien; Ma, Teng

2014-01-01

180

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

PubMed

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

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

2013-01-01

181

The effects of spheroid formation of adipose-derived stem cells in a microgravity bioreactor on stemness properties and therapeutic potential.  

PubMed

Adipose-derived stem cells (ADSCs) represent a valuable source of stem cells for regenerative medicine, but the loss of their stemness during invitro expansion remains a major roadblock. We employed a microgravity bioreactor (MB) to develop a method for biomaterial-free-mediated spheroid formation to maintain the stemness properties of ADSCs. ADSCs spontaneously formed three-dimensional spheroids in the MB. Compared with monolayer culture, the expression levels of E-cadherin and pluripotent markers were significantly upregulated in ADSC spheroids. Spheroid-derived ADSCs exhibited increased proliferative ability and colony-forming efficiency. By culturing the spheroid-derived ADSCs in an appropriate induction medium, we found that the multipotency differentiation capacities of ADSCs were significantly improved by spheroid culture in the MB. Furthermore, when ADSCs were administered to mice with carbon tetrachloride-induced acute liver failure, spheroid-derived ADSCs showed more effective potentials to rescue liver failure than ADSCs derived from constant monolayer culture. Our results suggest that spheroid formation of ADSCs in an MB enhances their stemness properties and increases their therapeutic potential. Therefore, spheroid culture in an MB can be an efficient method to maintain stemness properties, without the involvement of any biomaterials for clinical applications of invitro cultured ADSCs. PMID:25522961

Zhang, Shichang; Liu, Ping; Chen, Li; Wang, Yingjie; Wang, Zhengguo; Zhang, Bo

2015-02-01

182

Effects of Orthopaedic Polymer Particles on Chemotaxis of Macrophages and Mesenchymal Stem Cells  

PubMed Central

Wear particles generated from total joint arthroplasty (TJA) stimulate macrophages to release chemokines. The role of chemokines released from wear particle-stimulated macrophages on the migration of macrophages and osteoprogenitor cells in vitro has not been elucidated. In this study, we challenged murine macrophages (RAW 264.7) with clinically relevant polymethyl methacrylate (PMMA, 1-10 ?m) and ultra high molecular weight polyethylene (UHMWPE, 2-3 ?m) particles. The chemotactic effects of the conditioned media (CM) were tested in vitro using human macrophages (THP-1) and human mesenchymal stem cells (MSCs) as the migrating cells. CM collected from both particle types had a chemotactic effect on human macrophages, which could be eliminated by monocyte chemotactic protein-1 (MCP-1) neutralizing antibody. Blocking the CCR1 receptor eliminated the chemotactic effect, while CCR2 antibody only partially decreased THP-1 cell migration. CM from PMMA but not UHMWPE-exposed macrophages led to chemotaxis of MSCs; this effect could be eliminated by macrophage inflammatory protein-1 alpha (MIP-1?) neutralizing antibody. Neither CCR1 nor CCR2 blocking antibodies showed an effect on the migration of MSCs. Chemokines released by macrophages stimulated by wear particles can have an effect on the migration of macrophages and MSCs. This effect seems to be dependent on the particle type, and may be modulated by MCP-1 and MIP-1?, however more than one chemokine may be necessary for chemotaxis. PMID:20694994

Huang, Zhinong; Ma, Ting; Ren, Pei-Gen; Smith, R. Lane; Goodman, Stuart B

2010-01-01

183

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

184

Adult skeletal muscle stem cells.  

PubMed

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

Sambasivan, Ramkumar; Tajbakhsh, Shahragim

2015-01-01

185

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

186

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

PubMed

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

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

2015-04-01

187

``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

188

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

PubMed

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

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

2012-04-12

189

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 14days 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

190

CD11c+ Cells Partially Mediate the Renoprotective Effect Induced by Bone Marrow-Derived Mesenchymal Stem Cells  

PubMed Central

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

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

2013-01-01

191

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

PubMed Central

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

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

2014-01-01

192

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

PubMed

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

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

2014-01-01

193

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

PubMed Central

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

Baghaban Eslaminejad, Mohamadreza; Fallah, Nasrin

2013-01-01

194

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

PubMed

The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying molecular mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approximately 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2. PMID:22197704

Tamm, Christoffer; Galit, Sara Pijuan; Annern, Cecilia

2012-02-15

195

Measuring stem cell circadian rhythm.  

PubMed

Circadian rhythms are biological rhythms that occur within a 24-h time cycle. Sleep is a prime example of a circadian rhythm and with it melatonin production. Stem cell systems also demonstrate circadian rhythms. This is particularly the case for the proliferating cells within the system. In fact, all proliferating cell populations exhibit their own circadian rhythm, which has important implications for disease and the treatment of disease. Stem cell chronobiology is particularly important because the treatment of cancer can be significantly affected by the time of day a drug is administered. This protocol provides a basis for measuring hematopoietic stem cell circadian rhythm for future stem cell chronotherapeutic applications. PMID:25388388

Hrushesky, William; Rich, Ivan N

2015-01-01

196

The Effect of Cidofovir on Adenovirus Plasma DNA Levels in Stem Cell Transplantation Recipients without T Cell Reconstitution.  

PubMed

Cidofovir is frequently used to treat life-threatening human adenovirus (HAdV) infections in immunocompromised children after hematopoietic stem cell transplantation (HSCT). However, the antiviral effect irrespective of T cell reconstitution remains unresolved. Plasma HAdV DNA levels were monitored by real-time quantitative PCR during 42 cidofovir treatment episodes for HAdV viremia in 36 pediatric allogeneic HSCT recipients. HAdV load dynamics were related to T and natural killer (NK) cell reconstitution measured by flow cytometry. To evaluate the invivo antiadenoviral effect of cidofovir, we focused on 20 cidofovir treatment episodes lacking concurrent T cell reconstitution. During 2 to 10weeks of follow-up in the absence of T cells, HAdV load reduction (n=7) or stabilization (n=8) was observed in 15 of 20 treatments. Although HAdV load reduction was always accompanied by NK cell expansion, HAdV load stabilization was measured in 2 children lacking both T and NK cell reconstitution. In cases with T cell reconstitution, rapid HAdV load reduction (n=14) or stabilization (n=6) was observed in 20 of 22 treatments. In the absence of T cells, cidofovir treatment was associated with HAdV viremia control in the majority of cases. Although the contribution of NK cells cannot be excluded, cidofovir has the potential to mediate HAdV load stabilization in the time pending Tcell reconstitution. PMID:25464118

Lugthart, Gertjan; Oomen, Marloes A; Jol-van der Zijde, Cornelia M; Ball, Lynne M; Bresters, Dorine; Kollen, Wouter J W; Smiers, Frans J; Vermont, Clementien L; Bredius, Robbert G M; Schilham, Marco W; van Tol, Maarten J D; Lankester, Arjan C

2015-02-01

197

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

NASA Technical Reports Server (NTRS)

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

Kigel, J.; Cosgrove, D. J.

1991-01-01

198

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

EPA Science Inventory

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

199

Salinomycin exerts anticancer effects on human breast carcinoma MCF-7 cancer stem cells via modulation of Hedgehog signaling.  

PubMed

Breast cancer tissue contains a small population of cells that have the ability to self-renew, these cells are known as breast cancer stem cells (BCSCs). The Hedgehog signal transduction pathway plays a central role in stem cell development, its aberrant activation has been shown to contribute to the development of breast cancer, making this pathway an attractive therapeutic target. Salinomycin (Sal) is a novel identified cancer stem cells (CSCs) killer, however, the molecular basis for its anticancer effects is not yet clear. In the current study, Sal's ability to modulate the activity of key elements in the Hedgehog pathway was examined in the human breast cancer cell line MCF-7, as well as in a subpopulation of cancer stem cells identified within this cancer cell line. We show here that Sal inhibits proliferation, invasion, and migration while also inducing apoptosis in MCF-7 cells. Interestingly, in a subpopulation of MCF-7 cells with the CD44(+)/CD24(-) markers and high ALDH1 levels indicative of BCSCs, modulators of Hedgehog signaling Smo and Gli1 were significantly down-regulated upon treatment with Sal. These results demonstrate that Sal also inhibits proliferation and induces apoptosis of BCSCs, further establishing it as therapeutically relevant in the context of breast cancers and also indicating that modulation of Hedgehog signaling is one potential mechanism by which it exerts these anticancer effects. PMID:25499043

Lu, Ying; Ma, Wei; Mao, Jun; Yu, Xiaotang; Hou, Zhenhuan; Fan, Shujun; Song, Bo; Wang, Huan; Li, Jiazhi; Kang, Le; Liu, Pixu; Liu, Quentin; Li, Lianhong

2015-02-25

200

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

SciTech Connect

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

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

2012-02-15

201

Effect of cryopreservation on biological and immunological properties of stem cells from apical papilla.  

PubMed

Stem cells from apical papilla (SCAP) are a novel population of multipotent stem cells that, although similar to dental pulp stem cells, are a discrete source of dental stem cells. SCAP have potential roles in root development, apexogenesis, pulp/dentin regeneration, and bioroot engineering. However, procedures to store and preserve SCAP for future clinical applications have not been explored. In this study, we compared human freshly isolated SCAP (fSCAP) with cryopreserved SCAP (cSCAP) in terms of cell viability, colony-forming efficiency, cell proliferation rate, multilineage differentiation potential, profiles of mesenchymal stem cell (MSC) markers, karyotype analysis, and immunological assays. cSCAP showed a similar viable cell ratio, colony-forming efficiency, cell proliferation rate, multilineage differentiation potential, MSC surface markers, apoptotic rate, and G-banded karyotype when compared to fSCAP. There was no significant difference between fSCAP and cSCAP with regard to immune properties. In addition, cSCAP of miniature pig possessed the similar proliferation rate, differentiation potential, and immunomodulatory function as seen in fSCAP. This study demonstrates that cryopreservation does not affect the biological and immunological properties of SCAP, supporting the feasibility of SCAP cryopreservation in nitrogen. PMID:20082304

Ding, Gang; Wang, Wei; Liu, Yi; An, Yunqing; Zhang, Chunmei; Shi, Songtao; Wang, Songlin

2010-05-01

202

Stem cells in the eye  

Microsoft Academic Search

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

Mike Boulton; Julie Albon

2004-01-01

203

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

204

The Effect of Freezing on the Recovery and Expansion of Umbilical Cord Blood Hematopoietic Stem Cells  

Microsoft Academic Search

Objectives:Cell populations residing in waste tissues (cord blood, umbilical cord, and placenta) may be collected without any medical or ethical contraindications concerning the mother or newborn baby. Cord blood hematopoietic stem cells are routinely used for clinical transplants; however, the low cell dose of the graft limits their therapeutic efficacy as it is associated with increased delayed or failed engraftment.

Amal El Beshlawy; Hala G. Metwally; Khalil Abd El Khalek; Rania A. Zayed; Rania F. Hammoud; Somaia M. Mousa

2009-01-01

205

Effect of Cbfa1 on osteogenic differentiation of mesenchymal stem cells under hypoxia condition  

PubMed Central

Objective: To observe the effect of Cbfa1 on biological characteristics of marrow mesenchymal stem cells under hypoxia. Methods: The second passage of the MSCs were transfected with Cbfa1 and then cultured in 20% O2 and 3% O2 condition individually. The biological features of the cultured MSCs were assessed by the Real-time PCR. Results: After transfected with Cbfa1, the morphology of MSCs was no significant difference between two oxygen concentrations; The RT-PCR examination revealed that the expression of Cbfa1, BMP, OPN and VEGF in MSCs was higher than those before Cbfa1 transfection (P<0.05), especial the expression of Cbfa1 (P<0.05). Conclusion: After transfected with Cbfa1, cell morphology or growth cycle of MSCs was not significantly affected, but its osteogenic differentiation potential enhanced, particularly its osteogenic differentiation potential under hypoxia enhanced. PMID:24753746

Li, Zhang-Hua; Liao, Wen; Zhao, Qiang; Huan, Tang; Feng, Pan; Wei, Xia; Yi, Yang; Shao, Ning-Sheng

2014-01-01

206

Mimicking Stem Cell Niches to Increase Stem Cell Expansion  

PubMed Central

Summary Niches regulate lineage-specific stem cell self-renewal vs. differentiation in vivo and are comprised of supportive cells and extracellular matrix components arranged in a 3-dimensional topography of controlled stiffness in the presence of oxygen and growth factor gradients. Mimicking stem cell niches in a defined manner will facilitate production of the large numbers of stem cells needed to realize the promise of regenerative medicine and gene therapy. Progress has been made in mimicking components of the niche. Immobilizing cell-associated Notch ligands increased the self-renewal of hematopoietic (blood) stem cells. Culture on a fibrous scaffold that mimics basement membrane texture increased the expansion of hematopoietic and embryonic stem cells. Finally, researchers have created intricate patterns of cell-binding domains and complex oxygen gradients. PMID:18725291

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

2008-01-01

207

Stem Cell-Based Therapies for Ischemic Stroke  

PubMed Central

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

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

2014-01-01

208

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

PubMed Central

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

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

2014-01-01

209

Nuclear receptor regulation of stemness and stem cell differentiation  

PubMed Central

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

Jeong, Yangsik

2009-01-01

210

Enhancing spontaneous stem cell healing (Review).  

PubMed

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

2014-03-01

211

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.

212

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

213

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

PubMed Central

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

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

2013-01-01

214

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)

2003-09-12

215

Blood and Marrow Stem Cell Transplant  

MedlinePLUS

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

216

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 ...

Grcio, Filipe

217

Special stem cells for bone.  

PubMed

Mesenchymal stem cells (MSCs) are multipotential in vitro, but their endogenous properties are poorly defined. In this issue of Cell Stem Cell, Park et al. (2012) report that an MSC-like, osteolineage-directed Mx1+ population generates new osteoblasts at sites of bone damage, suggesting its potential for skeletal repair and regeneration. PMID:22385649

Zaidi, Mone; Sun, Li; Blair, Harry C

2012-03-01

218

Endodermal Stem Cell Populations Derived from Pluripotent Stem Cells  

PubMed Central

The generation of functional endodermal lineages, such as hepatocytes and pancreatic endocrine cells, from pluripotent stem cells remains a challenge. One strategy to enhance the purity, yield and maturity of endodermal derivatives is to expand endoderm committed stem or progenitor cell populations derived from pluripotent stem cells prior to final differentiation. Recent studies have shown that this is in fact a viable option both for expanding pure populations of endodermal cells as well as for generating more mature derivative tissues, as highlighted in the case of pancreatic beta cells. PMID:23452824

Cheng, Xin; Tyaboonchai, Amita; Gadue, Paul

2014-01-01

219

Engineering stem cells for future medicine.  

PubMed

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

Ricotti, Leonardo; Menciassi, Arianna

2013-03-01

220

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, Jos Maria; Martino, Sabata; Orlacchio, Aldo

2011-01-01

221

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

222

Effect of transplantation of bone marrow stem cells on myocardial infarction size in a rabbit model  

PubMed Central

BACKGROUND: Intravenous transplantation has been regarded as a most safe method in stem cell therapies. There is evidence showing the homing of bone marrow stem cells (BMSCs) into the injured sites, and thus these cells can be used in the treatment of acute myocardial infarction (MI). This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model. METHODS: A total of 60 New Zealand rabbits were randomly divided into three groups: control group, epicardium group (group I) and ear vein group (group II). The BMSCs were collected from the tibial plateau in group I and group II, cultured and labeled. In the three groups, rabbits underwent thoracotomy and ligation of the middle left anterior descending artery. The elevation of ST segment >0.2 mV lasting for 30 minutes on the lead II and III of electrocardiogram suggested successful introduction of myocardial infarction. Two weeks after myocardial infarction, rabbits in group I were treated with autogenous BMSCs at the infarct region and those in group II received intravenous transplantation of BMSCs. In the control group, rabbits were treated with PBS following thoracotomy. Four weeks after myocardial infarction, the heart was collected from all rabbits and the infarct size was calculated. The heart was cut into sections followed by HE staining and calculation of infarct size with an image system. RESULTS: In groups I and II, the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group (P<0.05). However, there was no significant difference in the infarct size between groups I and II (P>0.05). CONCLUSION: Transplantation of BMSCs has therapeutic effect on MI. Moreover, epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction. PMID:25215138

Ji, Li-li; Long, Xiao-feng; Tian, Hui; Liu, Yu-fei

2013-01-01

223

Nanog reverses the effects of organismal aging on mesenchymal stem cell proliferation and myogenic differentiation potential  

PubMed Central

Although the therapeutic potential of mesenchymal stem cells (MSC) is widely accepted, loss of cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSC originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Here we tested the hypothesis that a single pluripotency associated transcription factor, namely Nanog, may reverse the proliferation and differentiation potential of BM-MSC from adult donors. Microarray analysis showed that adult (a)BM-MSC expressing Nanog clustered close to Nanog-expressing neonatal cells. Nanog markedly upregulated genes involved in cell cycle, DNA replication and DNA damage repair and enhanced the proliferation rate and clonogenic capacity of aBM-MSC. Notably, Nanog reversed the myogenic differentiation potential and restored the contractile function of aBM-MSC to a similar level as that of neonatal (n)BM-MSC. The effect of Nanog on contractility was mediated at least in part - through activation of the TGF-? pathway by diffusible factors secreted in the conditioned medium of Nanog-expressing BM-MSC. Overall, our results suggest that Nanog may be used to overcome the effects of organismal aging on aBM-MSC, thereby increasing the potential of MSC from aged donors for cellular therapy and tissue regeneration. PMID:22949105

Han, Juhee; Mistriotis, Panagiotis; Lei, Pedro; Wang, Dan; Liu, Song; Andreadis, Stelios T.

2012-01-01

224

The effect of elastic biodegradable polyurethane electrospun nanofibers on the differentiation of mesenchymal stem cells.  

PubMed

Biodegradable polyurethane (PU) was synthesized based on using poly(?-caprolactone) (PCL) as the soft segment. Fibers in different diameters (200-400nm, 600-800nm, and 1.4-1.6?m) were then made by electrospinning PU solution in N,N-dimethylacetamide and 2,2,2-trifluoroethanol. Human bone marrow derived mesenchymal stem cells (hMSCs) in the form of single dispersed cells or aggregates were seeded on the electrospun meshes for evaluation of cell behavior. Differentiation experiments showed that hMSC aggregates on electrospun fibers had greater differentiation capacities than single cells. Besides, nanofibers of 200-400nm diameters significantly promoted the osteogenic and chondrogenic differentiation of hMSCs than fibers of the other diameters. The effect of substrate elasticity was further elucidated by comparing cell behaviors on the nanofibers of PCL-based PU and those of pure PCL. The more elastic PU nanofibers demonstrated more osteogenic and chondrogenic induction potential than PCL electrospun fibers. We suggested that the elastic nanofibers seeded with hMSC aggregates may be advantageous for cartilage and bone tissue engineering. PMID:25087022

Kuo, Yi-Chia; Hung, Shih-Chieh; Hsu, Shan-hui

2014-10-01

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

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 cell therapies in clinical trials 6. Patentability of human embryonic stem cell therapies 7. Creation

Rambaut, Andrew

227

Stem cells in gastroenterology and hepatology  

Microsoft Academic Search

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

Michael Quante; Timothy C. Wang

2009-01-01

228

Cell Stem Cell Endogenous Bone Marrow MSCs  

E-print Network

). The existence of multipotent bone marrow stromal cells (BMSCs), or skeletal/mesenchymal stem cells (SSCs of cultured cells (Sacchetti et al., 2007). Similar multipotent MSCs can be isolated from mouse bone marrowCell Stem Cell Article Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants

Mootha, Vamsi K.

229

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

230

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

PubMed

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

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

2015-02-15

231

Effect of nanodiamond modification of siloxane surfaces on stem cell behaviour  

NASA Astrophysics Data System (ADS)

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

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

2014-12-01

232

Effect of fibroblasts on breast cancer cell mammosphere formation and regulation of stem cell-related gene expression.  

PubMed

The purpose of this study was to investigate the regulatory effects of breast cancer fibroblasts (BCFs) vs. normal mammary fibroblasts (NMFs) on mammosphere formation and stem cell-related gene expression in breast cancer cells. Breast cancer cells (MCF-7) were cultured in suspension to generate primary and secondary mammospheres. The proportion of CD44+/CD24low/- cells was assessed by flow cytometry (FCM), and Wnt1, Notch1, ?-catenin, CXCR4, SOX2 and ALDH3A1 gene expression was detected by quantitative real-time PCR. The fibroblasts from either breast cancer tissue or normal mammary tissue were purified from tissue specimens and co-cultured with breast cancer cells. The mammosphere formation efficacy was approximately 180/10,000 MCF-7 cells. FCM analysis showed that, compared to the 2.1% positive expression in the MCF-7 monolayer culture cells, the expression of CD44+/CD24low/- in MCF-7 mammosphere cells was significantly elevated to 10.4% (P<0.01). The proportion of the CD44+/CD24low/- subpopulation of the cells in mammospheres was nearly 5-fold higher than that of general MCF-7 cells. Compared with MCF-7 monolayer culture cells, mammosphere cells showed significantly (P<0.01) enhanced expression of Wnt1 [fold-change (FC), 2.25], Notch1 (FC, 2.45), ?-catenin (FC, 1.72), CXCR4 (FC, 4.68), SOX2 (FC, 4.25) and ALDH3A1 (FC, 5.38). When BCFs were co-cultured with MCF-7 cells under mammosphere culture conditions, the length of time of mammosphere formation decreased, the volume of the mammo-spheres increased and the mammosphere-forming efficiency (MFE) was higher than that of NMFs and the control group. Both the BCF and NMF groups showed enhanced gene expression for the following genes: Wnt1 (FC, 3.18 and 1.27, respectively), ?-catenin (FC, 1.75 and 1.22, respectively), Notch1 (FC, 2.09 and 1.31, respectively), CXCR4 (FC, 2.77 and 1.33, respectively), SOX2 (FC, 2.77 and 1.80, respectively) and ALDH3A1 (FC, 5.23 and 1.85, respectively). Cancer fibroblast cells can promote the MFE and up-regulate stem cell-related gene expression in breast cancer cells. PMID:21573501

Zhang, Fengchun; Song, Caili; Ma, Yue; Tang, Lei; Xu, Yingchun; Wang, Hongxia

2011-09-01

233

University of Michigan developmental cancer stem cell vaccine shows antitumor effect  

Cancer.gov

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

234

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

NASA Astrophysics Data System (ADS)

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

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

235

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

NASA Astrophysics Data System (ADS)

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

Dulgar-Tulloch, Aaron Joseph

2005-11-01

236

Effects of pseudowollastonite (CaSiO 3) bioceramic on in vitro activity of human mesenchymal stem cells  

Microsoft Academic Search

We report the effects of two pseudowollastonite (?-CaSiO3) substrates on the attachment, viability, proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSCs), and provide detailed mechanistic links of surface texture, soluble factors and culture media to cell activities. Cell attachment and viability were lower for psWf (fine-grained, roughness 0.74?m) than for psWc (coarse-grained, roughness 1.25?m) surface, and were ascribed

Nianli Zhang; James A. Molenda; John H. Fournelle; William L. Murphy; Nita Sahai

2010-01-01

237

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

PubMed Central

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

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

2014-01-01

238

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

239

Stem cell tracking using iron oxide nanoparticles.  

PubMed

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

240

Harvard Stem Cell Institute  

NSDL National Science Digital Library

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

2009-11-09

241

Harvard Stem Cell Institute  

NSDL National Science Digital Library

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

242

Effect of intracerebral transplantation of mesenchymal stem cells on reactivity of pial arterioles in old rats.  

PubMed

Using a TV device for studying microcirculation (160), we analyzed the responses of arterioles in the pia mater of the sensorimotor cortex in young (2-3 months) and old (22-24 months) rats after local application of a vasoconstrictor (norepinephrine, 10(-6) M) or vasodilator (acetylcholine, 10(-6) M). The responses of the arterioles were evaluated by changes in their diameter and by the number of responding vessels in the field of view. The constrictor responses of the pial arteries to norepinephrine did not significantly differ in intact young and old rats. The number and degree of dilatory responses to acetylcholine in old rats were lower than in young animals by 14 and 30%, respectively. Intracerebral transplantation of mesenchymal stem cells to old rats had practically no effect on reactivity of pial arterioles to acetylcholine, while the number of constricted vessels in response to norepinephrine increased by ~20%. PMID:25257436

Sokolova, I B; Sergeev, I V; Anisimov, S V; Puzanov, M V; Dvoretskii, D P

2014-09-01

243

Angiogenic Effect of Mesenchymal Stem Cells as a Therapeutic Target for Enhancing Diabetic Wound Healing.  

PubMed

Impaired wound-healing activity in diabetes could result from several factors, including severely damaged angiogenic responses, which can affect wound healing process to cause delayed wound repair. Mesenchymal stem cells (MSCs) have been shown to enhance wound healing via multiple effects, including promoting angiogenesis both in vitro and in vivo; however, the mechanisms involved in enhancing diabetic wound healing are barely understood. This article reviews the recent literatures on MSCs treatment for promoting angiogenesis or vascularization in diabetic wounds and the potential mechanisms involved, with an emphasis on the role of paracrine soluble factors. Meanwhile, the potential benefits and related risks associated with the therapeutic use of MSCs have been presented and may lead to better understanding of the influence of MSCs without increasing potential risks. Further investigation will be required to determine the molecular basis of paracrine mechanisms and regulated angiogenesis of MSCs for its rational manipulation for impaired angiogenesis repair and diabetic wound healing. PMID:24861091

Gu, Chengwei; Huang, Sha; Gao, Dongyun; Wu, Yan; Li, Jiwei; Ma, Kui; Wu, Xu; Fu, Xiaobing

2014-05-25

244

Neurorescue effects and stem properties of chorionic villi and amniotic progenitor cells.  

PubMed

The capability to integrate into degenerative environment, release neurotrophic cytokines, contrast oxidative stress and an inherent differentiation potential towards siteappropriate phenotypes are considered crucial for the use of stem cells in tissue repair and regeneration. Nave human chorial villi- (hCVCs) and amniotic fluid- (hAFCs) derived cells, whose properties and potentiality have not been extensively investigated, may represent two novel foetal cell sources for stem cell therapy. We previously described that long-term transplantation of hAFCs in the lateral ventricles of wobbler and healthy mice was feasible and safe. In the present study we examine the in vitro intrinsic stem potential of hCVCs and hAFCs for future therapeutic applications in neurodegenerative disorders. Presence of stem lineages was evaluated assessing the expression pattern of relevant candidate markers by flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. Release of cytokines that may potentialy sustain endogenous neurogenesis and/or activate neuroprotective pathways was quantified by enzyme-linked immunosorbent assays (ELISAs). We also performed an in vitro neurorescue assay, wherein a neuroblastoma cell line damaged by 6-hydroxydopamine (6-OHDA) was treated with hCVC/hAFC-derived conditioned medium (CM). Nave hCVCs/hAFCs show a neurogenic/angiogenic predisposition. Both cell types express several specific neural stem/progenitor markers, such as nestin and connexin 43, and release significant amounts of brain-derived neurotrophic factor, as well as vascular endothelial growth factor. hCVC and hAFC populations comprise several interesting cell lineages, including mesenchymal stem cells (MSCs) and cells with neural-like phenotypes. Moreover, although CMs obtained from both cell cultures actively sustained metabolic activity in a 6-OHDA-induced Parkinson's disease (PD) cell model, only hCVC-derived CMs significantly reduced neurotoxin-induced apoptosis. In conclusion, this study demonstrates that nave hAFCs and hCVCs may enhance cell-recovery following neuronal damage through multiple rescue mechanisms, and may provide a suitable means of stem cell therapy for neurodegenerative disorders including PD. PMID:23291343

Calzarossa, C; Bossolasco, P; Besana, A; Manca, M P; De Grada, L; De Coppi, P; Giardino, D; Silani, V; Cova, L

2013-03-27

245

New Technology, New Law: Stem Cell Products  

E-print Network

management system and to comply with FDA regulations pertaining to safety andsafety of stem cell products through its risk-reduction and risk-management system.safety and effectiveness of their products. Honest participation in the risk- management system

Munzer, Stephen R.

2013-01-01

246

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

PubMed

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

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

2005-01-01

247

Effect of ascorbic acid on bone marrow-derived mesenchymal stem cell proliferation and differentiation.  

PubMed

Mesenchymal stem cells (MSCs) derived from bone marrow are an important tool in tissue engineering and cell-based therapies because of their multipotent capacity. Majority of studies on MSCs have investigated the roles of growth factors, cytokines, and hormones. Antioxidants such as ascorbic acid can be used to expand MSCs while preserving their differentiation ability. Moreover, ascorbic acid can also stimulate MSC proliferation without reciprocal loss of phenotype and differentiation potency. In this study, we evaluated the effects of ascorbic acid on the proliferation, differentiation, extracellular matrix (ECM) secretion of MSCs. The MSCs were cultured in media containing various concentrations (0-500 microM) of L-ascorbate-2-phosphate (Asc-2-P) for 2 weeks, following which they were differentiated into adipocytes and osteoblasts. Ascorbic acid stimulated ECM secretion (collagen and glycosaminoglycan) and cell proliferation. Moreover, the phenotypes of the experimental groups as well as the differentiation potential of MSCs remained unchanged. The apparent absence of decreased cell density or morphologic change is consistent with the toxicity observed with 5-250 microM concentrations of Asc-2-P. The results demonstrate that MSC proliferation or differentiation depends on ascorbic acid concentration. PMID:18640597

Choi, Kyung-Min; Seo, Young-Kwon; Yoon, Hee-Hoon; Song, Kye-Yong; Kwon, Soon-Yong; Lee, Hwa-Sung; Park, Jung-Keug

2008-06-01

248

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

PubMed Central

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

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

2014-01-01

249

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.

250

The effect of gold nanoparticle size on osteogenic differentiation of adipose-derived stem cells.  

PubMed

There have been many medical applications based on gold nanoparticles (GNPs) over the past several centuries. Recently, researchers have focused on bone tissue engineering applications utilizing GNPs. The effect of various sizes of gold nanoparticles on the differentiation of human adipose-derived stem cells (ADSCs) into osteoblasts was investigated. The concentration of gold nanoparticles was fixed at 1?M and varying sizes of 15, 30, 50, 75 and 100nm (spherical GNPs) were used. The lack of cytotoxicity was confirmed by establishing viability of ADSCs using cell counting kit-8 (CCK-8) and live/dead assays. The results showed that each size of GNPs had no significant toxicity on ADSCs during 1week of incubation. Osteogenic differentiation of ADSCs was confirmed by alkaline phosphatase (ALP) staining, ALP activity, calcium deposition, and real time PCR experiments. It was found, through dark field assays and microscope cell images, that 30nm and 50nm GNPs were preferentially up taken into the ADSCs. As expected, all sizes of gold nanoparticles promoted the differentiation of ADSCs toward osteoblasts more than control. Among all sizes, 30 and 50nm GNPs appeared to have the highest differentiation rates. The data consistently demonstrated that 30 and 50nm GNPs are the most effective in promoting osteogenic differentiation of ADSCs. PMID:25454427

Ko, Wan-Kyu; Heo, Dong Nyoung; Moon, Ho-Jin; Lee, Sang Jin; Bae, Min Soo; Lee, Jung Bok; Sun, In-Cheol; Jeon, Hoon Bong; Park, Hun Kuk; Kwon, Il Keun

2015-01-15

251

Stem cells for spine surgery.  

PubMed

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

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

2015-01-26

252

Stem cells for spine surgery  

PubMed Central

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

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

2015-01-01

253

Regulating the leukaemia stem cell.  

PubMed

Leukaemia 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 centre on the frequencies of cancer stem cells, their potential hierarchical organisation and their degree of maturation. LSCs in acute myeloid leukaemia (AML) have recently been studied using mouse syngeneic models of leukaemia induced by MLL oncogenes. These studies have revealed that LSCs are more analogous to progenitor cells and employ embryonic stem cell-like genetic programmes 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

2009-12-01

254

Bioprinting for stem cell research.  

PubMed

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

Tasoglu, Savas; Demirci, Utkan

2013-01-01

255

Effects of melatonin on the proliferation and differentiation of rat adipose-derived stem cells  

PubMed Central

Background: Osteogenesis driven by adipose-derived stem cells (ADSCs) is regulated by physiological and pathological factors. Accumulating evidence from in vitro and in vivo experiments suggests that melatonin may have an influence on bone formation. However, little is known about the effects of melatonin on osteogenesis, which thus remains to be elucidated. This study was performed to determine whether melatonin at physiological concentrations (0.01-10 nM) could affect the in vitro proliferation and osteogenic differentiation of rat ADSCs. Materials and Methods: ADSCs were isolated from the fat of adult rats. After cell expansion in culture media and through three passages, osteogenesis was induced in a monolayer culture using osteogenic medium with or without melatonin at physiological concentrations (0.01-10 nM). After four weeks, the cultures were examined for mineralization by Alizarin Red S and von Kossa staining and for alkaline phosphatase (ALP) activity using an ALP kit. Cell viability and apoptosis were also assayed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay and flow cytometry, respectively. Results: The results indicated that at physiological concentrations, melatonin suppressed proliferation and differentiation of ADSCs. These data indicate that ADSCs exposed to melatonin, had a lower ALP activity in contrast to the cells exposed to osteogenic medium alone. Similarly, mineral deposition (calcium level) also decreased in the presence of melatonin. Flow cytometry confirmed that cell growth had decreased and that the numbers of apoptotic cells had increased. Conclusion: These results suggest that the physiological concentration of melatonin has a negative effect on ADSC osteogenesis. PMID:19753194

Zaminy, Arash; Kashani, Iraj Ragerdi; Barbarestani, Mohammad; Hedayatpour, Azim; Mahmoudi, Reza; Vardasbi, Safoura; Shokrgozar, Mohammad Ali

2008-01-01

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

Cell Stem Cell CNS-Resident Glial Progenitor/Stem Cells  

E-print Network

to this rule and provides a striking example of stem/precursor cell-mediated regeneration. RemyelinationCell 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 Regenerative

Richardson, William D.

258

Differentiation therapy: sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma  

PubMed Central

Background Recent studies have demonstrated that side population (SP) cells isolated from various cancer cell lines and primary tumors possess stem cell-like properties. Sesamin, a food-derived agent, possesses anti-cancer activities both in vitro and in vivo. The present study was designed to determine whether sesamin also have effects on cancer stem-like SP cells from gallbladder cancer (GBC). Methods In this study, we sorted SP cells by flow cytometry. SP cells were cultured and treated with sesamin. Tumor-sphere formation, colony formation, Matrigel invasion and tumorigenic potential were determined. Expression of nuclear NF-?B, IL-6, p-Stat3, Twist, E-cadherin and Vimentin was measured by Western blot, immunofluorescence staining or RT-PCR analysis. Nuclear NF-?B activity and IL-6 protein level were assessed with ELISA. Xenograft tumors were generated in nude mice. Results After treated with sesamin, SP cells differentiated into cells expressing the epithelial marker (E-cadherin). Sesamin effectively affected SP cells stem cell-like characteristics (i.e., tumor-sphere formation, colony-formation, Matrigel invasion), weakened the drug-resistance of SP cells and inhibited tumor growth both in vitro and in vivo. Treatment with sesamin significantly reduced the expression of nuclear NF-?B, IL-6, p-Stat3, Twist and Vimentin (a mesenchymal marker) in SP cells. Nuclear NF-?B activity and IL-6 level were also decreased after treatment with sesamin. Conclusion Food-derived sesamin directs the epithelial differentiation of cancer stem-like SP cells from GBC, which is associated with attenuation of NF-?B-IL-6-Stat3-Twist signal pathway. PMID:25038821

2014-01-01

259

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

260

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

261

Federal Policy on Stem Cell Research  

MedlinePLUS

... U.S. policy? More FAQs Links to related resources Stem Cell Research Center for Regenerative Medicine NIH Stem Cell Unit ... of Health (NIH) can support and conduct human stem cell research. The HHS Secretary, through the NIH Director, is ...

262

What's It Like to Donate Stem Cells?  

MedlinePLUS

... learn more Whats 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 ...

263

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 ...

264

Comparative effects of chlorhexidine and essential oils containing mouth rinse on stem cells cultured on a titanium surface.  

PubMed

Chlorhexidine (CHX) and Listerine (LIS), an essential oil compound, are the two commonly used adjunctive agents for mechanical debridement, for reducing the bacterial load in the treatment of peri-implant inflammation. However, antimicrobial agents have been reported to be cytotoxic to the alveolar bone cells and gingival epithelial cells. The present study was performed to examine the effects of antiseptics CHX and LIS, on the morphology and proliferation of stem cells. Stem cells derived from the buccal fat pad were grown on machined titanium discs. Each disc was immersed in CHX or LIS for 30 sec, 1.5 min or 4.5 min. Cell morphology was evaluated with a confocal laser microscope and the viability of the cells was quantitatively analyzed with the cell counting kit-8 (CCK-8). The untreated cells attached to the titanium discs demonstrated well-organized actin cytoskeletons. No marked alterations in the cytoskeletal organization were observed in any of the treated groups. The treatment with CHX and LIS of the titanium discs decreased the viability of the cells grown on the treated discs (P<0.05). The stem cells derived from the buccal fat pad were sensitive to CHX and LIS, and a reduction in cellular viability was observed when these agents were applied to the discs for 30 sec. Further studies are required to determine the optimal application time and concentration of this antimicrobial agent for maximizing the reduction of the bacterial load and minimizing the cytotoxicity to the surrounding cells. PMID:24567172

Park, Jun-Beom; Lee, Gil; Yun, Byeong Gon; Kim, Chang-Hyen; Ko, Youngkyung

2014-04-01

265

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

PubMed

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

2014-05-01

266

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, neurogenesisthe process of generating mature granule cells from adult neural stem cellsoccurs 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

267

Mesenchymal stem cells in immunoregulation  

Microsoft Academic Search

Mesenchymal stem cells are present within the bone marrow cavity and serve as a reservoir for the continuous renewal of various mesenchymal tissues. Recent studies suggest that mesenchymal stem cells modulate immune reactions in vitro and escape from immune surveillance in vivo. We provide herein a discussion of issues including the current research progress on the in vitro interactions of

Xi Chen; Marilyn Ann Armstrong; Gang Li

2006-01-01

268

A double mechanism for the mesenchymal stem cells' positive effect on pancreatic islets.  

PubMed

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

269

Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome  

Microsoft Academic Search

Parainfluenza virus (PIV) infections may be significant causes of morbidity and mortality in patients undergoing stem cell transplantation, but data regarding their impact on transplant-related mortality is limited. This study sought to determine the risk factors of PIV acquisition and progression to lower respiratory tract in- fection, their impact on transplant-related mortality, and the effectiveness of antivi- ral therapy. A

W. Garrett Nichols; Lawrence Corey; Ted Gooley; Chris Davis; Michael Boeckh

2001-01-01

270

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

Microsoft Academic Search

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

Rokhaya Diop; Song Li

2011-01-01

271

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

PubMed

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

272

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

273

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

PubMed

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

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

2014-05-01

274

Stem cell mechanics: Auxetic nuclei  

NASA Astrophysics Data System (ADS)

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

Wang, Ning

2014-06-01

275

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

PubMed

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

Ortega-Martnez, Sylvia; Trejo, Jos L

2015-02-15

276

Combination therapy of mesenchymal stem cells and serelaxin effectively attenuates renal fibrosis in obstructive nephropathy.  

PubMed

Chronic kidney disease (CKD) results from the development of fibrosis, ultimately leading to end-stage renal disease (ESRD). Although human bone marrow-derived mesenchymal stem cells (MSCs) can accelerate renal repair following acute injury, the establishment of fibrosis during CKD may affect their potential to influence regeneration capacity. Here we tested the novel combination of MSCs with the antifibrotic serelaxin to repair and protect the kidney 7 d post-unilateral ureteral obstruction (UUO), when fibrosis is established. Male C57BL6 mice were sham-operated or UUO-inured (n = 4-6) and received vehicle, MSCs (1 10(6)), serelaxin (0.5 mg/kg per d), or the combination of both. In vivo tracing studies with luciferin/enhanced green fluorescent protein (eGFP)-tagged MSCs showed specific localization in the obstructed kidney where they remained for 36 h. Combination therapy conferred significant protection from UUO-induced fibrosis, as indicated by hydroxyproline analysis (P < 0.001 vs. vehicle, P < 0.05 vs. MSC or serelaxin alone). This was accompanied by preserved structural architecture, decreased tubular epithelial injury (P < 0.01 vs. MSCs alone), macrophage infiltration, and myofibroblast localization in the kidney (both P < 0.01 vs. vehicle). Combination therapy also stimulated matrix metalloproteinase (MMP)-2 activity over either treatment alone (P < 0.05 vs. either treatment alone). These results suggest that the presence of an antifibrotic in conjunction with MSCs ameliorates established kidney fibrosis and augments tissue repair to a greater extent than either treatment alone.-Huuskes, B. M., Wise, A. F., Cox, A. J., Lim, E. X., Payne, N. L., Kelly, D. J., Samuel, C. S., Ricardo, S. D. Combination therapy of mesenchymal stem cells and serelaxin effectively attenuates renal fibrosis in obstructive nephropathy. PMID:25395452

Huuskes, Brooke M; Wise, Andrea F; Cox, Alison J; Lim, Ee X; Payne, Natalie L; Kelly, Darren J; Samuel, Chrishan S; Ricardo, Sharon D

2014-11-13

277

Effect of fgf-2 on collagen tissue regeneration by human vertebral bone marrow stem cells.  

PubMed

The effects of fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration by human bone marrow stem cells (hBMSCs) were investigated. hBMSCs were isolated from human vertebral body bone marrow during vertebral surgery and a population of hBMSCs with the characteristics of mesenchymal stem cells was observed. The FGF-2 treatment (5?ng/mL) affected on the colony-forming efficiency, proliferation, and in vitro differentiation of hBMSCs. Insoluble/soluble collagen and hydroxyproline synthesis was significantly enhanced in hBMSCs expanded with FGF-2 and the treatment of FGF-2 caused a reduction in the mRNA expression of collagen type I, but an increase of collagen types II and III along with lysyl oxidase family genes. Collagen formation was also examined using an in vivo assay model by transplanting hBMSCs into immunocompromised mice (n=4) and the histologic and immunohistochemical results revealed that significantly more collagen with a well-organized structure was formed by FGF-2-treated hBMSCs at 8 weeks posttransplantation (P<0.05). The DNA microarray assay demonstrated that genes related to extracellular matrix formation were significantly upregulated. To elucidate the underlying mechanism, chemical inhibitors against extracellular-signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) were treated and following downstream expression was observed. Collectively, FGF-2 facilitated the collagen-producing potency of hBMSCs both in vitro and in vivo, rendering them more suitable for use in collagen regeneration in the clinical field. PMID:25122057

Park, Dong-Soo; Park, Jung-Chul; Lee, Jung-Seok; Kim, Tae-Wan; Kim, Ki-Joon; Jung, Byung-Joo; Shim, Eun-Kyung; Choi, Eun-Young; Park, So-Yon; Cho, Kyoo-Sung; Kim, Chang-Sung

2015-01-15

278

Effects of Whartons jelly-derived mesenchymal stem cells on neonatal neutrophils  

PubMed Central

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

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

2015-01-01

279

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

280

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 didnt 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

281

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

282

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

PubMed

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

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

2014-08-01

283

Effect of reduced culture temperature on antioxidant defences of mesenchymal stem cells.  

PubMed

Mesenchymal stem cells (MSC) promise to be valuable therapeutic tools but, due to their low numbers, require considerable in vitro expansion before use. This leads to in vitro aging, the accumulation of intracellular oxidative damage, and subsequently a decreased potential for proliferation and differentiation. Optimised culture conditions might help to reduce oxidative damage in MSC in vitro, and therefore, as reduced temperature is known to reduce oxidative stress in other somatic cells, we have investigated the effect of reduced temperature on rat MSC viability, differentiation, and oxidative damage. Temperature reduction did not affect MSC viability but increased differentiation and reduced apoptosis. Oxidative-damage-related indices were improved; reactive oxide species, nitric oxide, thiobarbituric acid reactive substances, carbonyl, and lipofuscin levels were reduced and glutathione peroxidase and superoxide dimutase levels increased. Levels of antiapoptotic heat shock proteins (HSP-27, -70, and -90) were raised and levels of the proapoptotic HSP-60 reduced. These data demonstrate that culturing MSC at reduced temperature decreases the accumulation of oxidative damage and therefore would probably improve long-term viability and successful engraftment of MSC used for tissue engineering or cell therapeutic purposes. PMID:16814114

Stolzing, Alexandra; Scutt, Andrew

2006-07-15

284

STEM CELL NICHE: Structure and Function  

Microsoft Academic Search

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

Linheng Li; Ting Xie

2005-01-01

285

Effect of Mechanical Loading on Three-Dimensional Cultures of Embryonic Stem Cell-Derived Cardiomyocytes  

PubMed Central

Cardiomyocytes selected from murine embryonic stem cells (ESCs) using the cardiac-specific promoter alpha-myosin heavy chain were embedded into collagen and fibronectin scaffolds. A custom-built device was used to expose these constructs to mechanical loading (10% stretch at 1, 2, or 3 Hz) or no loading. Constructs were evaluated using reverse transcriptase polymerase chain reaction, histology, and immunohistochemistry. Mechanical loading significantly affected gene expression, and these changes were dependent on the frequency of stretch. A 1 Hz cyclical stretch resulted in significantly lower gene expression, whereas a 3 Hz cyclical stretch resulted in significantly greater gene expression than in unstretched controls. These constructs also developed cardiac-specific cell structures similar to those found in vivo. This study describes a 3-dimensional model to examine the direct effect of mechanical loading on the differentiation of ESC-derived cardiomyocytes embedded in a defined extracellular matrix scaffold. A technique was also developed to isolate the areas within the constructs undergoing the most homogeneous strain so that the effect of mechanical loading on gene expression could be directly evaluated. These experiments emphasize that ESC-derived cardiomyocytes are actively responding to cues from their environment and that those cues can drive phenotypic control and cardiomyocyte differentiation. PMID:18333804

SHIMKO, VALERIE F.; CLAYCOMB, WILLIAM C.

2008-01-01

286

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

287

Allogeneic stem cell transplantation.  

PubMed

Allogeneic stem cell transplantation (HSCT) requires the harvest of an adequate number of stem cells (SC) from a histocompatible donor and their infusion into a patient following a conditioning regimen. During the past 35 years, the role of HSCT has changed from an experimental procedure for terminally ill patients to a curative treatment. In 2003, 1170 procedures were registered in Italy (Italian Group for Blood and Marrow Transplantation). The main reported indications were as follows: leukemia, lymphoproliferative diseases, myelodysplasia, and nonmalignant diseases such as thalassemia and severe aplastic anemia. Important changes have been observed in the last 5 years: the shift from bone marrow to peripheral blood as the SC source, the increasing number of alternative donors such as unrelated, partially matched family donors and cord blood SC, and the new extra-hematological indications including solid tumors. Moreover, the development of nonmyeloablative conditioning regimens have allowed physicians to perform HSCT in patients with advanced age or important comorbidities. In contrast, the availability of the Tyrosine kinase inhibitor (STI-571) for treatment of patients affected by chronic myelogenous leukemia, which was formerly the main indication for HSCT, has produced a dramatic decrease in the number of transplantations in this setting. HSCT performed in the early phases of disease and in young patients offers more than a 50% cure rate. The transplant-related mortality still represents the greatest obstacle, ranging from 20%-30%, despite the less toxic conditioning regimens, high-resolution HLA typing, and better supportive care. GvHD and infections remain the main causes of morbidity. As regards relapses, they correlate with disease status at the time of transplantation. Promising results have been recently obtained with haploidentical and with cord blood SC transplantation also in adult patients. PMID:16182779

Bosi, A; Bartolozzi, B; Guidi, S

2005-01-01

288

Advances in Stem Cell Mobilization  

PubMed Central

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

Hopman, Rusudan K.; DiPersio, John F.

2014-01-01

289

PBS Online NewsHour: Adult Stem Cells  

NSDL National Science Digital Library

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

290

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

291

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 subjects 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

292

Gastrointestinal Side Effects and Adequacy of Enteral Intake in Hematopoietic Stem Cell Transplant Patients.  

PubMed

Background: Patients undergoing hematopoietic stem cell transplant (HSCT) can experience gastrointestinal (GI) side effects as a complication of the treatment. Limited research exists describing how the duration and severity of GI side effects influence the consumption of adequate calorie intake in this population. The purpose of this study was to assess differences in GI side effects between patients who consumed adequate calories compared with those who did not. Methods: The MD Anderson Symptom Inventory-Gastrointestinal (MDASI-GI) tool was used to record daily GI side effects of 72 HSCT patients. Daily calorie intake was determined via calorie counts. Data were collected from day of transplant until engraftment. Results: Median percentage of caloric needs consumed for all patients was 49.2% (interquartile range, 35.1-66.6). Calorie intake decreased from baseline to transplant day 8 as severity of GI symptoms increased. An inverse relationship between percentage of caloric needs met and MDASI-GI component score, MDASI-GI symptom score, and lack of appetite score was observed. The only significant difference in MDASI-GI symptom scores between those who consumed adequate calories and those who consumed inadequate calories was for diarrhea; subjects who consumed >60% of caloric needs had significantly lower median diarrhea scores. Conclusion: Most patients consumed <60% of their caloric needs from time of transplant to time of engraftment. More research is needed to provide insight into strategies to increase intake and to describe the implications of prolonged inadequate intake in HSCT patients. PMID:25227122

Walrath, Maegan; Bacon, Cheryl; Foley, Sharon; Fung, Henry C

2014-09-16

293

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

294

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

295

Coping and support effects on mothers' stress responses to their child's hematopoietic stem cell transplantation  

Microsoft Academic Search

A hematopoietic stem cell transplantation (HSCT) is used as a treatment for cancer or nonmalignant hematological disorders in children. Little information is known about how an HSCT affects the mothers of these patients. The purposes of this repeated measures study were to examine the stress responses of mothers at four times during their child's hospitalization for an HSCT and to

Audrey E Nelson; Margaret Shandor Miles; Michael J Belyea

1997-01-01

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 (35 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 Jordo; Nascimento-dos-Santos, Gabriel; Gubert, Fernanda; de Figueirdo, Ana Beatriz Padilha; Torres, Ana Luiza; Paredes, Bruno D.; Teixeira, Camila; Tovar-Moll, Fernanda; Mendez-Otero, Rosalia; Santiago, Marcelo F.

2014-01-01

297

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

PubMed Central

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

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

2015-01-01

298

The effect of temperature on the viability of human mesenchymal stem cells  

PubMed Central

Introduction Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs. Methods The viability of human MSCs was measured after incubating them at temperatures of 38C, 48C and 58C; durations 45seconds, 80seconds and 150seconds. A control group was kept at 37C and 5% carbon dioxide for the duration of the investigation (7days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlue assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnetts test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlue) and cell viability (Trypan Blue). Results Results showed that cell metabolism was not severely affected up to 48C/150seconds, while cells in the 58C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48C/150seconds were compared with the control group. Conclusions The study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48C for 150seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations. PMID:24238300

2013-01-01

299

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

300

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

SciTech Connect

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

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

2011-07-01

301

Effect of nano-structured bioceramic surface on osteogenic differentiation of adipose derived stem cells.  

PubMed

Tissue engineering strategies to construct vascularized bone grafts potentially revolutionize the treatment of massive bone loss. The surface topography of the grafts plays critical roles on bone regeneration, while adipose derived stem cells (ASCs) are known for their capability to promote osteogenesis and angiogenesis when applied to bone defects. In the present study, the effects of hydroxyapatite (HAp) bioceramic scaffolds with nanosheet, nanorod, and micro-nano-hybrid (the hybrid of nanorod and microrod) surface topographies on attachment, proliferation and osteogenic differentiation, as well as the expression of angiogenic factors of rat ASCs were systematically investigated. The results showed that the HAp bioceramic scaffolds with the micro-/nano-topography surfaces significantly enhanced cell attachment and viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteogenic markers and angiogenic factors of ASCs. More importantly, the biomimetic feature of the hierarchical micro-nano-hybrid surface topography showed the highest stimulatory effect. The activation in Akt signaling pathway was observed in ASCs cultured on HAp bioceramics with nanorod, and micro-nano-hybrid surface topographies. Moreover, these induction effects could be repressed by Akt signaling pathway inhibitor LY294002. Finally, the in vivo bone regeneration results of rat critical-sized calvarial defect models confirmed that the combination of the micro-nano-hybrid surface and ASCs could significantly enhance both osteogenesis and angiogenesis as compared with the control HAp bioceramic scaffold with traditional smooth surface. Our results suggest that HAp bioceramic scaffolds with micro-nano-hybrid surface can act as cell carrier for ASCs, and consequently combine with ASCs to construct vascularized tissue-engineered bone. PMID:25002263

Xia, Lunguo; Lin, Kaili; Jiang, Xinquan; Fang, Bing; Xu, Yuanjin; Liu, Jiaqiang; Zeng, Deliang; Zhang, Maolin; Zhang, Xiuli; Chang, Jiang; Zhang, Zhiyuan

2014-10-01

302

Polyester ?-assay chip for stem cell studies  

PubMed Central

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

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

2012-01-01

303

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

Microsoft Academic Search

The bone marrow is an important dose-limiting cell renewal tissue for chemotherapy, wide-field irradiation, and autologous bone marrow transplantion. Over the past 510 years a great deal has been discovered about the hematopoietic stem cell compartment. Although the toxicity associated with prolonged myelosuppression continues to limit the wider use of chemotherapy and irradiation, ways are being discovered to circumvent this

Peter Mauch; Louis Constine; Joel Greenberger; William Knospe; Jessie Sullivan; Jane L. Liesveld; H. Joachim Deeg

1995-01-01

304

The effect of X-rays and C-ions on pluripotent embryonic stem cells  

PubMed Central

Embryonic stem cells (ESC) are characterized by both the capacity of infinite self-renewal and the ability to give rise to all the three germ layers emphasizing the need to strictly control the genetic integrity. To date, ESC are a powerful tool in disease modeling, tissue engineering and drug testing. However, in the field of radiation research, their potential has not been exploited. We used the mouse ESC line D3 as a model to examine the effects of X-rays or C-ions (spread out Bragg peak, energy 106147MeV/u, average LET=75 keV/m) [ 1]. Doses of 0.55Gy were applied and endpoints such as cell cycle progression (measured by flow cytometry), apoptosis (microscopic analysis of cell nucleus morphology), induction of chromosome aberrations (mFISH analysis), presence of pluripotency markers Oct3/4 and SOX2 (western blotting) and differentiation capacity by means of an embryoid body formation assay were analyzed up to 17 days post-irradiation. The experiments show that cells undergo a transient G2 arrest following exposure. After G2 checkpoint release, an increase in the apoptotic index is observed for both radiation types (3.7-fold increase for 2Gy X-ray and 2.4-fold increase for 2Gy C-ions). C-ions induce more structural chromosomal aberrations in first cycle cells than X-rays. During subsequent cell divisions, the frequency of chromosome aberrations declines: After >7 population doublings (8 days after exposure), the aberration frequency in the progeny of X-ray exposed cells returns to the control level (7% aberrant cells), while the progeny of C-ion exposed cells still harbor significantly more aberrations than control cells, which is mainly due to transmissible translocations. The expression of pluripotency markers is maintained in cells surviving X-ray or C-ion exposure. This finding is supported by examining the differentiation capacity of ESC through the formation of embryoid bodies. Our experiments show that after X-ray or C-ion exposure, cells are able to develop spontaneous beating activity, indicating the differentiation ability into mesodermal cell lineages, i.e. beating cardiomyocytes. However, following C-ion exposure, the formation of beating clusters was delayed compared with control cells. Moreover, our chromosome studies revealed that unexposed cells carry a high frequency of numerical aberrations. These comprise trisomies of chromosome 8 and 11 with a frequency of 298% and 266% respectively, as well as nullisomy of chromosome Y with a frequency of 353%. Aneuploidy is a typical feature of mouse ESC and has been related to cell culture methods [ 2] and passage number. Because aneuploidy may affect gene expression and influence the properties of a cell population, the relevance of experiments based on mouse ESC is limited. To overcome this problem, we recently extended our studies to human ESC. Human ESC are known to be cytogenetically more stable than mouse ESC, and represent a model that is closer to human embryonic development. Indeed, first investigations revealed a lower faction of cells with numerical and structural aberrations in the human ESC line H9 [ 3] compared with the mouse ESC line D3 (2% vs. 73% and 3% vs. 7%, respectively).

Luft, Sabine; Pignalosa, Diana; Arrizabalaga, Onetsine; Nasonova, Elena; Helm, Alexander; Durante, Marco; Ritter, Sylvia

2014-01-01

305

Microbioreactors for Stem Cell Research  

NASA Astrophysics Data System (ADS)

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

Freytes, Donald O.; Vunjak-Novakovic, Gordana

306

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

307

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

PubMed

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

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

2013-01-01

308

Effect of Cr(VI) and Ni(II) metal ions on human adipose derived stem cells.  

PubMed

Environmental exposure of Cr(VI) and Ni(II) due to rapid industrialization causes adverse effects in living tissues. Small quantities of these ions also find their way into tissues when metal alloys are used as implants. Even though considerable research has been done on the effects due to their exposure in animal cells, there are only very few reports on how they can affect stem cells which have been shown to be found in adult tissues as well, albeit in small quantities. Hence this study was aimed at understanding how Cr(VI) and Ni(II) affect human adipose derived stem cells (hADSCs) in a cell culture environment. Our results indicate that both ions induce apoptosis in a concentration and time dependent manner with loss of mitochondrial membrane potential (MMP) and corresponding increase in caspase-3 activity. With regard to Ni(II), apoptosis seems to occur only in a small percentage of cells while necrosis is predominant. It can be inferred that the long term exposure of these metals may cause adverse effects in stem cell proliferation and differentiation. PMID:25326906

Indra, R; Purna Sai, K; Rajaram, A; Rajaram, Rama

2015-02-01

309

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

PubMed Central

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

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

2013-01-01

310

Synergistic effect of laminin and mesenchymal stem cells on tracheal mucosal regeneration.  

PubMed

Although several studies have been successfully undertaken of tracheal reconstruction in terms of the maintaining the framework of the graft, most cases of reconstruction failure have resulted from delayed mucosal regeneration. The purposes of this study were to evaluate whether laminin-coated asymmetrically porous membrane (APM) scaffold enhances mucosal regeneration, to compare the mucosalization capability with mesenchymal stem cell (MSC) seeded APM, and to determine whether laminin coating and MSC seeding has a synergistic effect on mucosal regeneration. We reconstructed the full-thickness anterior tracheal defect of 36 New Zealand White rabbits with the APM scaffold. MSCs were isolated from the rabbit's inguinal fat. The animals were divided into 4 groups by the presence of laminin coating on APM and application of MSC [Group I,-/- (laminin/MSC); Group II,-/+; Group III,+/-; Group IV,+/+]. Endoscopy and histologic evaluation were performed and the results were compared among the groups. The results showed that ciliated columnar epithelium was regenerated earlier in groups II and III than in group I. Furthermore, the application of laminin and MSC had synergistic effects on tracheal epithelial regeneration. These results demonstrate that tracheal reconstruction by laminin-coated APM seeded with MSCs is most effective in enhancing tracheal mucosalization, and appears to be promising strategy in the regenerative treatment of tracheal defects. PMID:25617133

Lee, Doh Young; Lee, Jin Ho; Ahn, Hee-Jin; Oh, Se Heang; Kim, Tae Ho; Kim, Hee-Bok; Park, Seok-Won; Kwon, Seong Keun

2015-03-01

311

Molecular Pathways: Stem Cell Quiescence  

PubMed Central

Adult stem cells are maintained in a quiescent state, but are able to exit quiescence and rapidly expand and differentiate in response to stress. The quiescent state appears to be necessary for preserving self-renewal of stem cells and a critical factor in resistance of cancer stem cells (CSC) to chemotherapy and targeted therapies. Limited knowledge of quiescence mechanisms has prevented significant advance in targeting of drug resistant quiescent CSC populations in the clinic. Thus improved understanding of the molecular mechanisms of quiescence in adult stem cells is critical for development of molecularly targeted therapies against quiescent CSC in different cancers. Recent studies have provided a better understanding of intrinsic and extrinsic regulatory mechanisms that control stem cell quiescence. It is now appreciated that the p53 gene plays a critical role in regulating stem cell quiescence. Other intrinsic regulatory mechanisms include the FoxO,, HIF-1? and NFATc1 transcription factors, and signaling through ATM and mTOR. Extrinsic microenvironmental regulatory mechanisms include Angiopoietin-1, TGF-?, BMP, TPO, N-Cadherin and integrin adhesion receptors, Wnt/?-catenin signaling and osteopontin. In this article, we review current advances in understanding normal stem cell quiescence, their significance for CSC quiescence and drug resistance, and the potential clinical applications of these findings. PMID:21593194

Li, Ling; Bhatia, Ravi

2011-01-01

312

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

PubMed

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

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

2015-01-01

313

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

PubMed Central

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

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

2014-01-01

314

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

PubMed

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

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

2014-08-01

315

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

316

Effects of valproic acid on gene expression during human embryonic stem cell differentiation into neurons.  

PubMed

The widely used antiepileptic drug valproic acid (VPA) is known to exhibit teratogenicity in the form of a failure of the neural tube in humans. Embryonic stem cells (ESCs) are reported to be a promising cell source for evaluating chemical teratogenicity, because they are capable of reproducing embryonic developmental model and enable reduction in the number of experimental animals used. We previously investigated 22 genes for which expressions are altered by teratogens, specifically focusing on neural differentiation of mouse ESCs. In the present study, expressions of the investigated genes were evaluated by quantitative real-time PCR and compared during differentiation of human ESCs into neurons with or without VPA. Under the conditions, almost all gene expressions significantly changed in VPA-containing culture. Specifically, in neural development-related genes such as DCX, ARX, MAP2, and NNAT, more than 2-fold expression was observed. The findings suggest that the genes focused on in this study may help to elucidate the teratogenic effects of VPA and might be a useful tool to analyze embryotoxic potential of chemicals in humans. PMID:24849673

Ehashi, Tomo; Suzuki, Noriyuki; Ando, Satoshi; Sumida, Kayo; Saito, Koichi

2014-06-01

317

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

PubMed Central

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

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

2013-01-01

318

Heterogeneity in cancer stem cells.  

PubMed

Accumulating evidence suggests that cancer stem cells (CSCs) are heterogeneous populations and their phenotypes are unstable. A number of intrinsic and extrinsic mechanisms contribute to CSC phenotypic variation. The existence of various CSC subpopulations which would lead to a rapid relapse after primary treatments might pose a problem for CSC targeted therapeutics. In order to develop more effective approaches to cancer therapeutics, more CSC-related surface markers or targeting molecules, as well as some novel targeting strategies should be explored. This review summarized the origin and performance of heterogeneity in CSCs and discussed their therapeutic implications. PMID:25444897

Wang, Anxin; Chen, Lisha; Li, Chunlin; Zhu, Yimin

2015-02-01

319

Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness  

PubMed Central

Pre-leukemic mutations are thought to promote clonal expansion of haematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness1; however, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative neoplasms and leukemia2. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all prior to leukemia initiation. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed cell cycle kinetics using H2B-GFP label retention and BrdU incorporation. NrasG12D had a bimodal effect on HSCs, increasing the rate at which some HSCs divide and reducing the rate at which others divide. This mirrored bimodal effects on reconstituting potential as rarely dividing NrasG12D HSCs outcompeted wild-type HSCs while frequently dividing NrasG12D HSCs did not. NrasG12D had these effects by promoting STAT5 signaling, inducing different transcriptional responses in different subsets of HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through bimodal effects on HSC gene expression, cycling, and reconstituting potential. PMID:24284627

Li, Qing; Ng, Victor; Magee, Jeffrey; Chen, Shann-Ching; Shannon, Kevin; Morrison, Sean J.

2014-01-01

320

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

PubMed Central

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

2014-01-01

321

Sources of Stem Cells for Transplant  

MedlinePLUS

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

322

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

PubMed Central

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

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

2011-01-01

323

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.

324

Planarian Regeneration and Stem Cells  

NSDL National Science Digital Library

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

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

2007-03-31

325

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.

326

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

PubMed Central

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

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

2014-01-01

327

Hematopoietic Stem Cell Aging: Wrinkles In Stem Cell Potential  

Microsoft Academic Search

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

S. M. Chambers; M. A. Goodell

2007-01-01

328

Stem Cells . Author manuscript Astrocytes reverted to a neural progenitor-like state with transforming  

E-print Network

Keywords Animals ; Astrocytes ; drug effects ; metabolism ; radiation effects ; Brain Neoplasms ; chemically induced ; physiopathology ; Cell Dedifferentiation ; drug effects ; physiology ; radiation effects ; physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Stem Cell Transplantation ; Stem Cells ; drug effects

Paris-Sud XI, Université de

329

Effect of bone marrow mesenchymal stem cell transplantation on acute hepatic failure in rats.  

PubMed

The aim of the present study was to investigate the effectiveness of bone marrow mesenchymal stem cell (BMSC) transplantation in the treatment of acute hepatic failure (AHF) in rats. BMSCs were isolated from rat bone marrow, cultured and analyzed by flow cytometry. Following BMSC transplantation into rats with AHF, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), direct bilirubin (DBIL) and indirect bilirubin (IBIL) in the serum were measured using an automatic biochemical analyzer. Hematoxylin and eosin (H&E) staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to analyze the pathological changes and apoptosis rate. Levels of cluster of differentiation (CD)163 and interleukin (IL)-10 in the serum and liver tissue were detected by an enzyme-linked immunosorbent assay (ELISA) assay and western blot analysis. Compared with the levels in the control group, the serum levels of ALT, AST, DBIL, IBIL, CD163 and IL-10 in the BMSC transplantation groups were significantly lower at 120 and 168 h, while the serum levels of ALB were significantly higher at 168 h after BMSC transplantation. The pathological features of liver failure were alleviated by BMSC transplantation. The expression levels of CD163 and IL-10 in the liver tissue were also significantly decreased following transplantation. The results indicate that BMSCs have a therapeutic effect on AHF in rats, and CD163 and IL-10 may be used as sensitive serum prognosis indicators in the early assessment of patients following liver transplantation. PMID:25187814

Yuan, Shufang; Jiang, Tao; Zheng, Rongjiong; Sun, Lihua; Cao, Guiqiu; Zhang, Yuexin

2014-10-01

330

Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats  

PubMed Central

Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

Calatrava-Ferreras, Luca; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jimnez-Escrig, Adriano; Richart Lpez, Luis Alberto; Bazn, Eulalia

2012-01-01

331

Inhibition of Nuclear Nox4 Activity by Plumbagin: Effect on Proliferative Capacity in Human Amniotic Stem Cells  

PubMed Central

Human amniotic fluid stem cells (AFSC) with multilineage differentiation potential are novel source for cell therapy. However, in vitro expansion leads to senescence affecting differentiation and proliferative capacities. Reactive oxygen species (ROS) have been involved in the regulation of stem cell pluripotency, proliferation, and differentiation. Redox-regulated signal transduction is coordinated by spatially controlled production of ROS within subcellular compartments. NAD(P)H oxidase family, in particular Nox4, has been known to produce ROS in the nucleus; however, the mechanisms and the meaning of this function remain largely unknown. In the present study, we show that Nox4 nuclear expression (nNox4) increases during culture passages up to cell cycle arrest and the serum starvation causes the same effect. With the decrease of Nox4 activity, obtained with plumbagin, a decline of nuclear ROS production and of DNA damage occurs. Moreover, plumbagin exposure reduces the binding between nNox4 and nucleoskeleton components, as Matrin 3. The same effect was observed also for the binding with phospho-ERK, although nuclear ERK and P-ERK are unchanged. Taken together, we suggest that nNox4 regulation may have important pathophysiologic effects in stem cell proliferation through modulation of nuclear signaling and DNA damage. PMID:24489986

Guida, Marianna; Maraldi, Tullia; Resca, Elisa; Beretti, Francesca; Zavatti, Manuela; Bertoni, Laura; La Sala, Giovanni B.; De Pol, Anto

2013-01-01

332

Advances in stem cell therapy for spinal cord injury  

PubMed Central

Spinal cord injury (SCI) is a devastating condition producing great personal and societal costs and for which there is no effective treatment. Stem cell transplantation is a promising therapeutic strategy, though much preclinical and clinical research work remains. Here, we briefly describe SCI epidemiology, pathophysiology, and experimental and clinical stem cell strategies. Research in stem cell biology and cell reprogramming is rapidly advancing, with the hope of moving stem cell therapy closer to helping people with SCI. We examine issues important for clinical translation and provide a commentary on recent developments, including termination of the first human embryonic stem cell transplantation trial in human SCI. PMID:23114605

Mothe, Andrea J.; Tator, Charles H.

2012-01-01

333

Combination stem cell therapy for heart failure  

E-print Network

stem cells prolongs the survival of a semiallogeneic heart transplantstem cells: isolation, characterization, and differentiation. Cell Transplantstem cells from human umbilical cord blood. Cell Transplant

2010-01-01

334

RETINOIDS REGULATE STEM CELL DIFFERENTIATION  

PubMed Central

Retinoids are ubiquitous signaling molecules that influence nearly every cell type, exert profound effects on development, and complement cancer chemotherapeutic regimens. All-trans retinoic acid (RA) and other active retinoids are generated from vitamin A (retinol), but key aspects of the signaling pathways required to produce active retinoids remain unclear. Retinoids generated by one cell type can affect nearby cells, so retinoids also function in intercellular communication. RA induces differentiation primarily by binding to RARs, transcription factors that associate with RXRs and bind RAREs in the nucleus. Binding of RA: (1) initiates changes in interactions of RAR/RXRs with co-repressor and co-activator proteins, activating transcription of primary target genes; (2) alters interactions with proteins that induce epigenetic changes; (3) induces transcription of genes encoding transcription factors and signaling proteins that further modify gene expression (e.g., FOX03A, Hoxa1, Sox9, TRAIL, UBE2D3); and (4) results in alterations in estrogen receptor? signaling. Proteins that bind at or near RAREs include Sin3a, N-CoR1, PRAME, Trim24, NRIP1, Ajuba, Zfp423, and MN1/TEL. Interactions among retinoids, RARs/RXRs, and these proteins explain in part the powerful effects of retinoids on stem cell differentiation. Studies of this retinol signaling cascade enhance our ability to understand and regulate stem cell differentiation for therapeutic and scientific purposes. In cancer chemotherapeutic regimens retinoids can promote tumor cell differentiation and/or induce proteins that sensitize tumors to drug combinations. Mechanistic studies of retinoid signaling continue to suggest novel drug targets and will improve therapeutic strategies for cancer and other diseases, such as immune-mediated inflammatory diseases. PMID:20836077

Gudas, Lorraine J.; Wagner, John A.

2012-01-01

335

Effects of vitamin A on in vitro maturation of pre-pubertal mouse spermatogonial stem cells.  

PubMed

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(-6)M and retinol at 3.3.10(-7)M, as well as retinol 10(-6)M 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(-6)M retinol. RA and Re can control in vitro germ cell proliferation and differentiation. Re at a concentration of 10(-6)M 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; Mac, Bertrand; Cauliez, Bruno; Rives, Nathalie

2013-01-01

336

Stem cells, neural progenitors, and engineered stem cells.  

PubMed

Human pluripotent stem cellsHuman pluripotent stem cells (hPSCshPSCs ) have the unique potential to form every cell type in the body. This potential provides opportunities for generating humanhuman progenitorsprogenitors and other differentiated cell types for understanding human developmenthuman development and for use in cell type-specific therapiestherapies . Equally important is the ability to engineer stem cellsstem cells and their derived progenitors to mimic specific diseasedisease models. This chapter will focus on the propagationpropagation and characterization of human neural progenitorshuman neural progenitors (hNPshNPs ) derived from hPSCs with a particular focus on engineering hNPs to generate in vitroin vitro disease modelsdisease models for human neuro-mitochondrial disordersneuro-mitochondrial disorders . We will discuss the methodologies for culturing and characterizing hPSCs and hNPs; and protocols for engineering hNPs by using a novel mitochondrial transfectionmitochondrial transfection technology. PMID:25431071

Rao, Raj R; Iyer, Shilpa

2015-01-01

337

Effect of fibroblast growth factor 9 on the osteogenic differentiation of bone marrow stromal stem cells and dental pulp stem cells  

PubMed Central

The role of fibroblast growth factor 9 (FGF9) in bone formation may depend on gene dosage, developmental stage, cell type or interactions with other cytokines. In the present study bone marrow stromal stem cells (BMSCs) and dental pulp stem cells (DPSCs) were cultured and osteogenically induced in vitro, treated with exogenous FGF9 at varying concentrations. Alkaline phosphatase staining, alizarin red S staining, reverse transcription quantitative polymerase chain reaction and western blot analyses were performed in order to investigate the gene expression levels of osteogenic markers. The results of the present study demonstrated that FGF9 enhanced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) during osteogenic induction in BMSCs and DPSCs, which are derived from different tissues. FGF9 also inhibited the osteogenic differentiation of BMSCs and DPSCs through the activation of ERK1/2. These findings suggested that FGF9 may be an inhibitor of osteogenesis in mesenchymal stem cells in vitro and its application in vivo requires investigation in the future. PMID:25435023

LU, JINGTING; DAI, JIEWEN; WANG, XUDONG; ZHANG, MAOLIN; ZHANG, PENG; SUN, HAO; ZHANG, XIULI; YU, HONGBO; ZHANG, WENBIN; ZHANG, LEI; JIANG, XINQUAN; SHEN, STEVE GUOFANG

2015-01-01

338

Effect of fibroblast growth factor 9 on the osteogenic differentiation of bone marrow stromal stem cells and dental pulp stem cells.  

PubMed

The role of fibroblast growth factor 9 (FGF9) in bone formation may depend on gene dosage, developmental stage, cell type or interactions with other cytokines. In the present study bone marrow stromal stem cells (BMSCs) and dental pulp stem cells (DPSCs) were cultured and osteogenically induced in vitro, treated with exogenous FGF9 at varying concentrations. Alkaline phosphatase staining, alizarin red S staining, reverse transcription quantitative polymerase chain reaction and western blot analyses were performed in order to investigate the gene expression levels of osteogenic markers. The results of the present study demonstrated that FGF9 enhanced the phosphorylation of extracellular signal?regulated kinase 1/2 (ERK1/2) during osteogenic induction in BMSCs and DPSCs, which are derived from different tissues. FGF9 also inhibited the osteogenic differentiation of BMSCs and DPSCs through the activation of ERK1/2. These findings suggested that FGF9 may be an inhibitor of osteogenesis in mesenchymal stem cells in vitro and its application in vivo requires investigation in the future. PMID:25435023

Lu, Jingting; Dai, Jiewen; Wang, Xudong; Zhang, Maolin; Zhang, Peng; Sun, Hao; Zhang, Xiuli; Yu, Hongbo; Zhang, Wenbin; Zhang, Lei; Jiang, Xinquan; Shen, Steve Guofang

2015-03-01

339

BMP signaling and stem cell regulation  

Microsoft Academic Search

Stem cells play an essential role in cellular specialization and pattern formation during embryogenesis and in tissue regeneration in adults. This is mainly due to a stem cell's ability to replenish itself (self-renewal) and, at the same time, produce differentiated progeny. Realization of these special stem cell features has changed the prospective of the field. However, regulation of stem cell

Jiwang Zhang; Linheng Li

2005-01-01

340

Stem Cell Research: Elephants in the Room  

Microsoft Academic Search

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

NEIL D. THEISE

2003-01-01

341

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

342

Protective effect of acetyl-L-carnitine on propofol-induced toxicity in embryonic neural stem cells.  

PubMed

Propofol is a widely used general anesthetic. A growing body of data suggests that perinatal exposure to general anesthetics can result in long-term deleterious effects on brain function. In the developing brain there is evidence that general anesthetics can cause cell death, synaptic remodeling, and altered brain cell morphology. Acetyl-L-carnitine (L-Ca), an anti-oxidant dietary supplement, has been reported to prevent neuronal damage from a variety of causes. To evaluate the ability of L-Ca to protect against propofol-induced neuronal toxicity, neural stem cells were isolated from gestational day 14 rat fetuses and on the eighth day in culture were exposed for 24h to propofol at 10, 50, 100, 300 and 600 ?M, with or without L-Ca (10 ?M). Markers of cellular proliferation, mitochondrial health, cell death/damage and oxidative damage were monitored to determine: (1) the effects of propofol on neural stem cell proliferation; (2) the nature of propofol-induced neurotoxicity; (3) the degree of protection afforded by L-Ca; and (4) to provide information regarding possible mechanisms underlying protection. After propofol exposure at a clinically relevant concentration (50 ?M), the number of dividing cells was significantly decreased, oxidative DNA damage was increased and a significant dose-dependent reduction in mitochondrial function/health was observed. No significant effect on lactase dehydrogenase (LDH) release was observed at propofol concentrations up to 100 ?M. The oxidative damage at 50 ?M propofol was blocked by L-Ca. Thus, clinically relevant concentrations of propofol induce dose-dependent adverse effects on rat embryonic neural stem cells by slowing or stopping cell division/proliferation and causing cellular damage. Elevated levels of 8-oxoguanine suggest enhanced oxidative damage [reactive oxygen species (ROS) generation] and L-Ca effectively blocks at least some of the toxicity of propofol, presumably by scavenging oxidative species and/or reducing their production. PMID:24704589

Liu, Fang; Rainosek, Shuo W; Sadovova, Natalya; Fogle, Charles M; Patterson, Tucker A; Hanig, Joseph P; Paule, Merle G; Slikker, William; Wang, Cheng

2014-05-01

343

Immunotargeting of cancer stem cells  

PubMed Central

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

G?bka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

2015-01-01

344

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

345

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

346

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.

347

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

348

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

349

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

350

Programmable Mechanobioreactor for Exploration of the Effects of Periodic Vibratory Stimulus on Mesenchymal Stem Cell Differentiation  

PubMed Central

Abstract A programmable bioreactor using a voice-coil actuator was developed to enable research on the effects of periodic vibratory stimulus on human and porcine mesenchymal stem cells (MSCs). We hypothesized that low frequency vibrations would result in a cartilage phenotype and higher frequency vibrations would result in a bone phenotype. The mechanical stimulation protocol is adjusted from a computer external to the incubator via a USB cable. Once programmed, the embedded microprocessor and sensor system on the bioreactor execute the protocol independent of the computer. In each test, a sinusoidal stimulus was applied to a culture plate in 1-min intervals with a 15-min rest following each, for a total of 15?h per day for 10 days. Frequencies of 1 and 100?Hz were applied to cultures of both human and porcine umbilical cordderived 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.

2014-01-01

351

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

352

Effect of CNT on collagen fiber structure, stiffness assembly kinetics and stem cell differentiation.  

PubMed

Collagen is a native one-dimensional nanomaterial. Carbon nanotube (CNT) was found to interface with biological materials and show promising applications in creating reinforced scaffolds for tissue engineering and regenerative medicine. In this study, we examined the unique role of CNT in collagen fiber structure, mechanical strength and assembly kinetics. The results imply that CNT interacts with collagen at the molecular level. It relaxes the helical coil of collagen fibrils and has the effect of flattening the fibers leading to the elongation of D-period, the characteristic banding feature of collagen fibers. The surface charge of oxidized CNT leads to enhanced local ionic strength during collagen fibrillogenesis, accounting for the slower kinetics of collagen-CNT (COL-CNT) fiber assembly and the formation of thicker fibers. Due to the rigidity of CNT, the addition of CNT increases the fiber stiffness significantly. When applied as a matrix for human decidua parietalis placental stem cells (hdpPSCs) differentiation, COL-CNT was found to support fast and efficient neural differentiation ascribed to the elongated D-period. These results highlight the superiority of CNT to modulate collagen fiber assembly at the molecular level. The study also exemplifies the use of CNT to enhance the functionality of collagen for biological and biomedical applications. PMID:25686951

Kim, Taeyoung; Sridharan, Indumathi; Zhu, Bofan; Orgel, Joseph; Wang, Rong

2015-04-01

353

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

Microsoft Academic Search

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

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

354

Effect of Cyclic Strain on Cardiomyogenic Differentiation of Rat Bone Marrow Derived Mesenchymal Stem Cells  

Microsoft Academic Search

Mesenchymal stem cells (MSCs) are a potential source of material for the generation of tissue-engineered cardiac grafts because of their ability to transdifferentiate into cardiomyocytes after chemical treatments or co-culture with cardiomyocytes. Cardiomyocytes in the body are subjected to cyclic strain induced by the rhythmic heart beating. Whether cyclic strain could regulate rat bone marrow derived MSC (rBMSC) differentiation into

Yan Huang; Lisha Zheng; Xianghui Gong; Xiaoling Jia; Wei Song; Meili Liu; Yubo Fan

2012-01-01

355

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

356

[Effect of hydroxyurea on the number of hematopoietic stem cells, stromal cell precursors and cell precursors of thymus lymphoid tissue in the bone marrow of mice during aging].  

PubMed

The concentration of hemopoietic stem cells (colony-forming cells in the spleen - CFC-S) decreases in the bone marrow of CBA mice during ageing, whereas the concentration of precursors for stromal fibroblasts (colony-forming cells for fibroblasts-CFC-F) increases. The total numbers of nucleated cells, CFC-S and CFC-F in the bone marrow of old mice essentially increase. Hydroxyurea, administered in vivo, does not effect the concentration of CFC-S, but it increases CFC-F concentration in the bone marrow of mice. Hydroxyurea produces just the same suppressive effect on the numbers of nucleated cells, CFC-S and CFC-F in the mice of different ages, and stimulates the capacity of bone marrow donors to repopulate the thymus of the irradiated young recipients. PMID:6485091

Sidorenko, A V; Andrianova, L F

1984-07-01

357

Stem cells in veterinary medicine.  

PubMed

The stem cell field in veterinary medicine continues to evolve rapidly both experimentally and clinically. Stem cells are most commonly used in clinical veterinary medicine in therapeutic applications for the treatment of musculoskeletal injuries in horses and dogs. New technologies of assisted reproduction are being developed to apply the properties of spermatogonial stem cells to preserve endangered animal species. The same methods can be used to generate transgenic animals for production of pharmaceuticals or for use as biomedical models. Small and large animal species serve as valuable models for preclinical evaluation of stem cell applications in human beings and in veterinary patients in areas such as spinal cord injury and myocardial infarction. However, these applications have not been implemented in the clinical treatment of veterinary patients. Reviews on the use of animal models for stem cell research have been published recently. Therefore, in this review, animal model research will be reviewed only in the context of supporting the current clinical application of stem cells in veterinary medicine. PMID:21371354

Fortier, Lisa A; Travis, Alexander J

2011-01-01

358

Progress and prospects in stem cell therapy  

PubMed Central

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future. PMID:23736002

Xu, Xiu-ling; Yi, Fei; Pan, Hui-ze; Duan, Shun-lei; Ding, Zhi-chao; Yuan, Guo-hong; Qu, Jing; Zhang, Hai-chen; Liu, Guang-hui

2013-01-01

359

Evaluation of a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay (SOT)  

EPA Science Inventory

The Embryonic Stem Cell Test (EST) has been used to evaluate the effects of xenobiotics using three endpoints, stem cell differentiation, stem cell viability and 3T3-cell viability. Our research goal is to establish amodel system that would evaluate chemical effects using a singl...

360

[Stem cell factor production from cultured nasal epithelial cells--effect on SCF production by drugs].  

PubMed

We studied whether epithelial cells cultured in serum-free medium contained other cells or not, there were differences in SCF production from cultured nasal epithelial cells between groups of nonallergic and allergic patients, and among degrees of serum mite-CAP RAST classes of allergic patients, and how drugs inhibited SCF production. As a result, no other contaminating cells except mast cell existed in cultured cells. There was a significant difference in SCF production of cultured cells between nonallergic and class 1-2, 3-4, 5-6, and between class 1-2 and 3-4, 5-6 of mite CAP-RAST class. Cyclosporin, prednisolone, fluticasone, ketotifen, and clemastine inhibited SCF production from cultured epithelial cells, but cromoglicate and suplatast did not. Inhibition means the reduction of SCF from cells, not the growth of cultured nasal epithelial cells. PMID:11905054

Koyama, Mamoru; Otsuka, Hirokuni; Kusumi, Taeko; Yamauchi, Yoko

2002-02-01

361

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. ...

362

Future Research in Adipose Stem Cell Engineering  

Microsoft Academic Search

\\u000a Adipose stem cells have a bright prospect in regenerative medicine for tissue\\/organ engineering. However, some hurdles may\\u000a hinder the progress of adipose stem cell engineering. Therefore this chapter highlights the advances in adipose stem cell\\u000a researches, and focuses on prospective researches that are needed to overcome the hurdles in adipose stem cell engineering,\\u000a i.e., to identify the various stem cells

Jeanne Adiwinata Pawitan

363

Mesenchymal stem cells for cardiac cell therapy.  

PubMed

Despite refinements of medical and surgical therapies, heart failure remains a fatal disease. Myocardial infarction is the most common cause of heart failure, and only palliative measures are available to relieve symptoms and prolong the patient's life span. Because mammalian cardiomyocytes irreversibly exit the cell cycle at about the time of birth, the heart has traditionally been considered to lack any regenerative capacity. This paradigm, however, is currently shifting, and the cellular composition of the myocardium is being targeted by various regeneration strategies. Adult progenitor and stem cell treatment of diseased human myocardium has been carried out for more than 10 years (Menasche et al., 2001; Stamm et al., 2003), and it has become clear that, in humans, the regenerative capacity of hematopoietic stem cells and endothelial progenitor cells, despite potent proangiogenic effects, is limited (Stamm et al., 2009). More recently, mesenchymal stem cells (MSCs) and related cell types are being evaluated in preclinical models of heart disease as well as in clinical trials (see Published Clinical Trials, below). MSCs have the capacity to self-renew and to differentiate into lineages that normally originate from the embryonic mesenchyme (connective tissues, blood vessels, blood-related organs) (Caplan, 1991; Prockop, 1997; Pittenger et al., 1999). The current definition of MSCs includes plastic adherence in cell culture, specific surface antigen expression (CD105(+)/CD90(+)/CD73(+), CD34(-)/CD45(-)/CD11b(-) or CD14(-)/CD19(-) or CD79?(-)/HLA-DR1(-)), and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic) (Dominici et al., 2006 ). If those criteria are not met completely, the term "mesenchymal stromal cells" should be used for marrow-derived adherent cells, or other terms for MSC-like cells of different origin. For the purpose of this review, MSCs and related cells are discussed in general, and cell type-specific properties are indicated when appropriate. We first summarize the preclinical data on MSCs in models of heart disease, and then appraise the clinical experience with MSCs for cardiac cell therapy. PMID:21062128

Choi, Yeong-Hoon; Kurtz, Andreas; Stamm, Christof

2011-01-01

364

Dose dependent side effect of superparamagnetic iron oxide nanoparticle labeling on cell motility in two fetal stem cell populations.  

PubMed

Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies. PMID:24244310

Diana, Valentina; Bossolasco, Patrizia; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

2013-01-01

365

Dose Dependent Side Effect of Superparamagnetic Iron Oxide Nanoparticle Labeling on Cell Motility in Two Fetal Stem Cell Populations  

PubMed Central

Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies. PMID:24244310

Diana, Valentina; Bossolasco, Patrizia; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

2013-01-01

366

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.

367

Biomaterials for stem cell differentiation  

Microsoft Academic Search

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

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

2008-01-01

368

Effects of low frequency electromagnetic fields on the chondrogenic differentiation of human mesenchymal stem cells.  

PubMed

Electromagnetic fields (EMF) have been shown to exert beneficial effects on cartilage tissue. Nowadays, differentiated human mesenchymal stem cells (hMSCs) are discussed as an alternative approach for cartilage repair. Therefore, the aim of this study was to examine the impact of EMF on hMSCs during chondrogenic differentiation. HMSCs at cell passages five and six were differentiated in pellet cultures in vitro under the addition of human fibroblast growth factor 2 (FGF-2) and human transforming growth factor-?(3) (TGF-?(3) ). Cultures were exposed to homogeneous sinusoidal extremely low-frequency magnetic fields (5?mT) produced by a solenoid or were kept in a control system. After 3 weeks of culture, chondrogenesis was assessed by toluidine blue and safranin-O staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR) for cartilage-specific proteins, and a DMMB dye-binding assay for glycosaminoglycans. Under EMF, hMSCs showed a significant increase in collagen type II expression at passage 6. Aggrecan and SOX9 expression did not change significantly after EMF exposure. Collagen type X expression decreased under electromagnetic stimulation. Pellet cultures at passage 5 that had been treated with EMF provided a higher glycosaminoglycan (GAG)/DNA content than cultures that had not been exposed to EMF. Chondrogenic differentiation of hMSCs may be improved by EMF regarding collagen type II expression and GAG content of cultures. EMF might be a way to stimulate and maintain chondrogenesis of hMSCs and, therefore, provide a new step in regenerative medicine regarding tissue engineering of cartilage. PMID:21452358

Mayer-Wagner, Susanne; Passberger, Alice; Sievers, Birte; Aigner, Joachim; Summer, Burkhard; Schiergens, Tobias S; Jansson, Volkmar; Mller, Peter E

2011-05-01

369

Effects of Different Doses of Bone Morphogenetic Protein 4 on Viability and Proliferation Rates of Mouse Embryonic Stem Cells  

Microsoft Academic Search

Received: 20\\/Jul\\/2008, Accepted: 2\\/Nov\\/2008 Objective: In this study, we examined the effect of different doses of bone morpho- genetic protein 4 (BMP4) on CCE mouse embryonic stem cells (ESCs) viability and proliferation rates in order to improve the outcome of induction processes and make a system with highest viability and proliferation rates for further studies on BMP4 roles in multiple

Zohreh Makoolati; Mansoureh Movahedin; Mehdi Forouzandeh-Moghadam

2009-01-01

370

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation  

Microsoft Academic Search

Ovarian failure after allogeneic stem cell transplant (allo-SCT) is an important risk factor for development of osteoporosis. We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT. A total of 60 women with osteoporosis or osteopenia were divided randomly into four groups of 15 women each. Group 1 was treated with calcium and

L Tauchmanov; G De Simone; T Musella; F Orio; P Ricci; C Nappi; G Lombardi; A Colao; B Rotoli; C Selleri

2006-01-01

371

Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells  

PubMed Central

Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed. PMID:24212632

Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

2011-01-01

372

Cell Stem Cell Wnt Proteins Are Self-Renewal Factors  

E-print Network

Cell Stem Cell Article Wnt Proteins Are Self-Renewal Factors for Mammary Stem Cells and Promote.03.020 SUMMARY Adult stem cells have the ability to self-renew and to generate specialized cells. Self the organ develops postnatally, arises from stem cells, and is readily generated from transplanted cells. We

Bejerano, Gill

373

Ferreting out stem cells from their niches  

Microsoft Academic Search

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

Valerie Horsley; Elaine Fuchs

2011-01-01

374

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

PubMed Central

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

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

2014-01-01

375

Effects of the Endocrine-Disrupting Chemical DDT on Self-Renewal and Differentiation of Human Mesenchymal Stem Cells  

PubMed Central

Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear. Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology. Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs. Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPAR?), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells. Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs. Citation: Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK, McLachlan JA, Nephew KP, Burow ME, Bunnell BA. 2015. Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human mesenchymal stem cells. Environ Health Perspect 123:4248;?http://dx.doi.org/10.1289/ehp.1408188 PMID:25014179

Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F.B.; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth P.

2014-01-01

376

Effects of nucleus pulposus cell-derived acellular matrix on the differentiation ofmesenchymal stem cells.  

PubMed

Recent attempts to treat disc degeneration with mesenchymal stem cells (MSCs) showed encouraging results. Differentiating MSCs towards nucleus pulposus cell (NPC)-like lineages represents a speculative mechanism. Niche factors including hypoxia, growth factors and cell-cell interactions have been suggested but the matrix niche factor has not been studied. Our collagen microencapsulation provides a 3D model to study matrix niche as it enables the encapsulated cells to remodel the template matrix. We previously demonstrated the chondro-inductive role of of chondrocytes-derived matrix in MSCs and showed that NPCs maintained their phenotype and remodeled the template matrix of collagen microspheres into a glycosaminoglycan (GAG)-rich one. Here we aim to study the effects of NPC-derived matrix on MSC differentiation towards NPC-like lineages by firstly producing an NPC-derived matrix in collagen microspheres, secondly optimizing a decellularization protocol to discard NPCs yet retaining the matrix, thirdly repopulating the acellular NPC-derived matrix with MSCs and fourthly evaluating their phenotype. Finally, we injected these microspheres in a pilot rabbit disc degeneration model. Results showed that NPCs survived, maintained their phenotypic markers and produced GAGs. A decellularization protocol with maximal removal of the NPCs, minimal loss in major matrix components and partial retention of NPC-specific markers was identified. The resulting acellular matrix supported MSC survival and matrix production, and up-regulated the gene expression of NPC markers including type II collagen and glypican 3. Finally, injection of MSC in these microspheres in rabbit degenerative disc better maintained hydration level with more pronounced staining of GAGs and type II collagen than controls. PMID:23465833

Yuan, Minting; Yeung, Chiu Wai; Li, Yuk Yin; Diao, Huajia; Cheung, K M C; Chan, D; Cheah, K; Chan, Pui Barbara

2013-05-01

377

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.

378

Effects of nanostructurized silicon on proliferation of stem and cancer cell.  

PubMed

In vitro experiments showed that stem and cancer cells retained their viability on the surface of porous silicon with 10-100 nm nanostructures, but their proliferation was inhibited. Silicon nanoparticles of 100 nm in size obtained by mechanical grinding of porous silicon films or crystal silicon plates in a concentration below 1 mg/ml in solution did not modify viability and proliferation of mouse fibroblast and human laryngeal cancer cells. Additional ultrasonic exposure of cancer cells in the presence of 1 mg/ml silicon nanoparticles added to nutrient medium led to complete destruction of cells or to the appearance of membrane defects blocking their proliferation and initiating their apoptotic death. PMID:22442808

Osminkina, L A; Luckyanova, E N; Gongalsky, M B; Kudryavtsev, A A; Gaydarova, A Kh; Poltavtseva, R A; Kashkarov, P K; Timoshenko, V Yu; Sukhikh, G T

2011-05-01

379

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

380

Human Stem Cells for Craniomaxillofacial Reconstruction  

PubMed Central

Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction. PMID:24564584

Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor

2014-01-01

381

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

382

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

383

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; 36 years old; 7.213.1 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. Rsum Contexte Les cellules souches adultes ont t largement tudies dans les approches de bio-ingnierie pour la thrapie de rparation tissulaire. Nous valuons l'efficacit clinique et la scurit de l'application de cellules souches msenchymateuses allogniques en culture drives de moelle osseuse (MSCs) pour le traitement de plaies cutanes dans un modle canin. Hypothse La transplantation de MSC allognique topique peut acclrer la fermeture en toute paisseur de plaies cutanes exprimentales et attnuer l'inflammation locale. Sujets Des chiens beagles adultes sains (n = 10; 36 ans; 7.213.1 kg) ont t tudis. Mthodes Des plaies cutanes en pleine paisseur ont t cres sur la face dorsale des beagles sains et des MSCs allognes ont t injectes par voie intradermique. Le taux de cicatrisation et le degr de production de collagne ont t analyss sur le plan histologique par colorations l'hmatoxyline et osine et par trichrome. Le degr de prolifration cellulaire et d'angiognse ont t valus par immunohistochimie l'aide d'anticorps spcifiques d'antigne nuclaire de prolifration cellulaire, de vimentine et d'actine de muscle lisse ?. Les taux d'expression local d'ARNm d'interleukine-2, d'interfron-?, du facteur de croissance basique de fibroblaste et de mtalloprotinase-2 de matrice, ont t valus par RT-PCR. Rsultats Compar avec les plaies traites par excipient, les plaies traites par les MSCs ont montr une plus rapide cicatrisation et une augmentation de synthse de collagne, de prolifration cellulaire er d'angiognse. En outre, Les plaies traites au MSC ont montr une expression diminue de cytokines pro-inflammatoires (interleukine-2 et interfron-?) et des facteurs lis 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

384

Curative effect and safety of intrathecal transplantation of neural stem cells for the treatment of cerebral hemorrhage.  

PubMed

In this study, we aimed to explore the curative effect and safety of neural stem cell intrathecal transplantation for the treatment of cerebral hemorrhage. We transplanted 4.0 x 10(8) neural stem cells per procedure into the subarachnoid space by lumbar puncture 7 days after cerebral hemorrhage, twice a week, a total of 4 times. NIHSS scores and brain CT scans were conducted to assess neural functions and the volume of perihematoma lesions in patients on days 1, 7, 14, 21, and 28. We found that the NIHSS scores and the volume of the perihematoma lesions were significantly reduced after day 14. The differences before and after treatment were highly significant