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Sample records for affect stem cell

  1. Genetic background affects susceptibility to tumoral stem cell reprogramming

    PubMed Central

    García-Ramírez, Idoia; Ruiz-Roca, Lucía; Martín-Lorenzo, Alberto; Blanco, Óscar; García-Cenador, María Begoña; García-Criado, Francisco Javier; Vicente-Dueñas, Carolina; Sánchez-García, Isidro

    2013-01-01

    The latest studies of the interactions between oncogenes and its target cell have shown that certain oncogenes may act as passengers to reprogram tissue-specific stem/progenitor cell into a malignant cancer stem cell state. In this study, we show that the genetic background influences this tumoral stem cell reprogramming capacity of the oncogenes using as a model the Sca1-BCRABLp210 mice, where the type of tumor they develop, chronic myeloid leukemia (CML), is a function of tumoral stem cell reprogramming. Sca1-BCRABLp210 mice containing FVB genetic components were significantly more resistant to CML. However, pure Sca1-BCRABLp210 FVB mice developed thymomas that were not seen in the Sca1-BCRABLp210 mice into the B6 background. Collectively, our results demonstrate for the first time that tumoral stem cell reprogramming fate is subject to polymorphic genetic control. PMID:23839033

  2. Stem Cells

    MedlinePlus

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

  3. Low Temperature Affects Stem Cell Maintenance in Brassica oleracea Seedlings

    PubMed Central

    de Jonge, Jennifer; Kodde, Jan; Severing, Edouard I.; Bonnema, Guusje; Angenent, Gerco C.; Immink, Richard G. H.; Groot, Steven P. C.

    2016-01-01

    Most of the above ground tissues in higher plants originate from stem cells located in the shoot apical meristem (SAM). Several plant species can suffer from spontaneous stem cell arrest resulting in lack of further shoot development. In Brassica oleracea this SAM arrest is known as blindness and occurs in an unpredictable manner leading to considerable economic losses for plant raisers and farmers. Detailed analyses of seedlings showed that stem cell arrest is triggered by low temperatures during germination. To induce this arrest reproducibly and to study the effect of the environment, an assay was developed. The role of genetic variation on the susceptibility to develop blind seedlings was analyzed by a quantitative genetic mapping approach, using seeds from a double haploid population from a cross between broccoli and Chinese kale, produced at three locations. The analysis revealed, besides an effect of the seed production location, a region on linkage group C3 associated with blindness sensitivity. A subsequent dynamic genome-wide transcriptome analysis resulted in the identification of around 3000 differentially expressed genes early after blindness induction. A large number of cell cycle genes were en masse induced early during the development of blindness, whereas shortly after, all were down-regulated. This miss-regulation of core cell cycle genes is accompanied with a strong reduction of cells reaching the DNA replication phase. From the differentially expressed genes, 90 were located in the QTL region C3. Among them are two genes belonging to the MINICHROMOSOMAL MAINTENANCE gene family, known to be involved in DNA replication, a RETINOBLASTOMA-RELATED gene, a key regulator for cell cycle initiation, and several MutS homologs genes, involved in DNA repair. These genes are potential candidates for being involved in the development of blindness in Brassica oleracea sensitive genotypes. PMID:27375654

  4. Low Temperature Affects Stem Cell Maintenance in Brassica oleracea Seedlings.

    PubMed

    de Jonge, Jennifer; Kodde, Jan; Severing, Edouard I; Bonnema, Guusje; Angenent, Gerco C; Immink, Richard G H; Groot, Steven P C

    2016-01-01

    Most of the above ground tissues in higher plants originate from stem cells located in the shoot apical meristem (SAM). Several plant species can suffer from spontaneous stem cell arrest resulting in lack of further shoot development. In Brassica oleracea this SAM arrest is known as blindness and occurs in an unpredictable manner leading to considerable economic losses for plant raisers and farmers. Detailed analyses of seedlings showed that stem cell arrest is triggered by low temperatures during germination. To induce this arrest reproducibly and to study the effect of the environment, an assay was developed. The role of genetic variation on the susceptibility to develop blind seedlings was analyzed by a quantitative genetic mapping approach, using seeds from a double haploid population from a cross between broccoli and Chinese kale, produced at three locations. The analysis revealed, besides an effect of the seed production location, a region on linkage group C3 associated with blindness sensitivity. A subsequent dynamic genome-wide transcriptome analysis resulted in the identification of around 3000 differentially expressed genes early after blindness induction. A large number of cell cycle genes were en masse induced early during the development of blindness, whereas shortly after, all were down-regulated. This miss-regulation of core cell cycle genes is accompanied with a strong reduction of cells reaching the DNA replication phase. From the differentially expressed genes, 90 were located in the QTL region C3. Among them are two genes belonging to the MINICHROMOSOMAL MAINTENANCE gene family, known to be involved in DNA replication, a RETINOBLASTOMA-RELATED gene, a key regulator for cell cycle initiation, and several MutS homologs genes, involved in DNA repair. These genes are potential candidates for being involved in the development of blindness in Brassica oleracea sensitive genotypes.

  5. Clearance kinetics of biomaterials affects stem cell retention and therapeutic efficacy.

    PubMed

    Lai, Chia Y; Wu, Pei J; Roffler, Steve R; Lee, Sho T; Hwang, Shiaw M; Wang, Shoei S; Wang, Kuan; Hsieh, Patrick C H

    2014-02-10

    The use of biomaterial carriers to improve the therapeutic efficacy of stem cells is known to augment cell delivery, retention, and viability. However, the way that carrier clearance kinetics boosts stem cell delivery and impacts stem cell function remains poorly characterized. In this study, we designed a platform to simultaneously quantify carrier clearance and stem cell retention to evaluate the impact of carrier clearance kinetics on stem cell retention. Additionally, a murine model of hindlimb ischemia was employed to investigate the effects of various cell retention profiles on mitigating peripheral arterial disease. To image the in vivo behaviors of material and cells, we used biotinylated hyaluronan with fluorescently labeled streptavidin and Discosoma sp. Red (Ds-Red)-expressing human mesenchymal stem cells. We found that the retention of transplanted stem cells was closely related to the remaining biomaterial. Furthermore, therapeutic effectiveness was also affected by stem cell retention. These results demonstrate that low-molecular-weight hyaluronan had a slow clearance and high cell retention profile, improving the therapeutic efficacy of human stem cells.

  6. Aging differentially affects male and female neural stem cell neurogenic properties

    PubMed Central

    Waldron, Jay; McCourty, Althea; Lecanu, Laurent

    2010-01-01

    Purpose Neural stem cell transplantation as a brain repair strategy is a very promising technology. However, despite many attempts, the clinical success remains very deceiving. Despite clear evidence that sexual dimorphism rules many aspects of human biology, the occurrence of a sex difference in neural stem cell biology is largely understudied. Herein, we propose to determine whether gender is a dimension that drives the fate of neural stem cells through aging. Should it occur, we believe that neural stem cell sexual dimorphism and its variation during aging should be taken into account to refine clinical approaches of brain repair strategies. Methods Neural stem cells were isolated from the subventricular zone of three- and 20-month-old male and female Long-Evans rats. Expression of the estrogen receptors, ERα and ERβ, progesterone receptor, androgen receptor, and glucocorticoid receptor was analyzed and quantified by Western blotting on undifferentiated neural stem cells. A second set of neural stem cells was treated with retinoic acid to trigger differentiation, and the expression of neuronal, astroglial, and oligodendroglial markers was determined using Western blotting. Conclusion We provided in vitro evidence that the fate of neural stem cells is affected by sex and aging. Indeed, young male neural stem cells mainly expressed markers of neuronal and oligodendroglial fate, whereas young female neural stem cells underwent differentiation towards an astroglial phenotype. Aging resulted in a lessened capacity to express neuron and astrocyte markers. Undifferentiated neural stem cells displayed sexual dimorphism in the expression of steroid receptors, in particular ERα and ERβ, and the expression level of several steroid receptors increased during aging. Such sexual dimorphism might explain, at least in part, the sex difference in neural fate we observed in young and old neural stem cells. These results suggest that sex and aging are two factors to be taken

  7. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

    SciTech Connect

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blueher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  8. Elastic modulus affects the growth and differentiation of neural stem cells

    PubMed Central

    Jiang, Xian-feng; Yang, Kai; Yang, Xiao-qing; Liu, Ying-fu; Cheng, Yuan-chi; Chen, Xu-yi; Tu, Yue

    2015-01-01

    It remains poorly understood if carrier hardness, elastic modulus, and contact area affect neural stem cell growth and differentiation. Tensile tests show that the elastic moduli of Tiansu and SMI silicone membranes are lower than that of an ordinary dish, while the elastic modulus of SMI silicone membrane is lower than that of Tiansu silicone membrane. Neural stem cells from the cerebral cortex of embryonic day 16 Sprague-Dawley rats were seeded onto ordinary dishes as well as Tiansu silicone membrane and SMI silicone membrane. Light microscopy showed that neural stem cells on all three carriers show improved adherence. After 7 days of differentiation, neuron specific enolase, glial fibrillary acidic protein, and myelin basic protein expression was detected by immunofluorescence. Moreover, flow cytometry revealed a higher rate of neural stem cell differentiation into astrocytes on Tiansu and SMI silicone membranes than on the ordinary dish, which was also higher on the SMI than the Tiansu silicone membrane. These findings confirm that all three cell carrier types have good biocompatibility, while SMI and Tiansu silicone membranes exhibit good mechanical homogenization. Thus, elastic modulus affects neural stem cell differentiation into various nerve cells. Within a certain range, a smaller elastic modulus results in a more obvious trend of cell differentiation into astrocytes. PMID:26604916

  9. Mesenchymal stem cells derived from adipose tissue are not affected by renal disease.

    PubMed

    Roemeling-van Rhijn, Marieke; Reinders, Marlies E J; de Klein, Annelies; Douben, Hannie; Korevaar, Sander S; Mensah, Fane K F; Dor, Frank J M F; IJzermans, Jan N M; Betjes, Michiel G H; Baan, Carla C; Weimar, Willem; Hoogduijn, Martin J

    2012-10-01

    Mesenchymal stem cells are a potential therapeutic agent in renal disease and kidney transplantation. Autologous cell use in kidney transplantation is preferred to avoid anti-HLA reactivity; however, the influence of renal disease on mesenchymal stem cells is unknown. To investigate the feasibility of autologous cell therapy in patients with renal disease, we isolated these cells from subcutaneous adipose tissue of healthy controls and patients with renal disease and compared them phenotypically and functionally. The mesenchymal stem cells from both groups showed similar morphology and differentiation capacity, and were both over 90% positive for CD73, CD105, and CD166, and negative for CD31 and CD45. They demonstrated comparable population doubling times, rates of apoptosis, and were both capable of inhibiting allo-antigen- and anti-CD3/CD28-activated peripheral blood mononuclear cell proliferation. In response to immune activation they both increased the expression of pro-inflammatory and anti-inflammatory factors. These mesenchymal stem cells were genetically stable after extensive expansion and, importantly, were not affected by uremic serum. Thus, mesenchymal stem cells of patients with renal disease have similar characteristics and functionality as those from healthy controls. Hence, our results indicate the feasibility of their use in autologous cell therapy in patients with renal disease.

  10. Passage number affects the pluripotency of mouse embryonic stem cells as judged by tetraploid embryo aggregation.

    PubMed

    Li, Xiang-Yun; Jia, Qing; Di, Ke-Qian; Gao, Shu-Min; Wen, Xiao-Hui; Zhou, Rong-Yan; Wei, Wei; Wang, Li-Ze

    2007-03-01

    The aim of this study was to determine whether the number of passages affected the developmental pluripotency of embryonic stem (ES) cells as measured by the attainment of adult fertile mice derived from embryonic stem (ES) cell/tetraploid embryo complementation. Thirty-six newborns were produced by the aggregation of tetraploid embryos and hybrid ES cells after various numbers of passages. These newborns were entirely derived from ES cells as judged by microsatellite DNA, coat-color phenotype, and germline transmission. Although 15 survived to adulthood, 17 died of respiratory failure, and four were eaten by their foster mother. From the 15 mice that reached adulthood and that could reproduce, none arose from ES cells at passage level 15 or more. All 15 arose from cells at passages 3-11. Our results demonstrate that the number of passages affects the developmental pluripotency of ES cells.

  11. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord.

    PubMed

    Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

    2014-09-15

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.

  12. Stem cells.

    PubMed

    Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

    2010-10-01

    Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.

  13. Types of Stem Cells

    MedlinePlus

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  14. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows.

    PubMed

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blüher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-13

    Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPARγ2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 μM) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 μM) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  15. Cell-free extract from porcine induced pluripotent stem cells can affect porcine somatic cell nuclear reprogramming.

    PubMed

    No, Jin-Gu; Choi, Mi-Kyung; Kwon, Dae-Jin; Yoo, Jae Gyu; Yang, Byoung-Chul; Park, Jin-Ki; Kim, Dong-Hoon

    2015-01-01

    Pretreatment of somatic cells with undifferentiated cell extracts, such as embryonic stem cells and mammalian oocytes, is an attractive alternative method for reprogramming control. The properties of induced pluripotent stem cells (iPSCs) are similar to those of embryonic stem cells; however, no studies have reported somatic cell nuclear reprogramming using iPSC extracts. Therefore, this study aimed to evaluate the effects of porcine iPSC extracts treatment on porcine ear fibroblasts and early development of porcine cloned embryos produced from porcine ear skin fibroblasts pretreated with the porcine iPSC extracts. The Chariot(TM) reagent system was used to deliver the iPSC extracts into cultured porcine ear skin fibroblasts. The iPSC extracts-treated cells (iPSC-treated cells) were cultured for 3 days and used for analyzing histone modification and somatic cell nuclear transfer. Compared to the results for nontreated cells, the trimethylation status of histone H3 lysine residue 9 (H3K9) in the iPSC-treated cells significantly decreased. The expression of Jmjd2b, the H3K9 trimethylation-specific demethylase gene, significantly increased in the iPSC-treated cells; conversely, the expression of the proapoptotic genes, Bax and p53, significantly decreased. When the iPSC-treated cells were transferred into enucleated porcine oocytes, no differences were observed in blastocyst development and total cell number in blastocysts compared with the results for control cells. However, H3K9 trimethylation of pronuclear-stage-cloned embryos significantly decreased in the iPSC-treated cells. Additionally, Bax and p53 gene expression in the blastocysts was significantly lower in iPSC-treated cells than in control cells. To our knowledge, this study is the first to show that an extracts of porcine iPSCs can affect histone modification and gene expression in porcine ear skin fibroblasts and cloned embryos.

  16. Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells

    PubMed Central

    Trevisan, Marta; Desole, Giovanna; Costanzi, Giulia; Lavezzo, Enrico; Palù, Giorgio; Barzon, Luisa

    2017-01-01

    Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts. The reprogramming efficiency of the methods based on episomal and Sendai virus vectors was higher than that of the retroviral vector-based approach. All human iPSC clones derived with the different methods showed the typical features of pluripotent stem cells, including the expression of alkaline phosphatase and stemness maker genes, and could give rise to the three germ layer derivatives upon embryoid bodies assay. Microarray analysis confirmed the presence of typical stem cell gene expression profiles in all iPSC clones and did not identify any significant difference among reprogramming methods. In conclusion, the use of different reprogramming methods is equivalent and does not affect gene expression profile of the derived human iPSCs. PMID:28117672

  17. Regulation of miRNAs Affects Radiobiological Response of Lung Cancer Stem Cells

    PubMed Central

    Xu, Yan-mei; Liao, Xing-yun; Chen, Xie-wan; Li, De-zhi; Sun, Jian-guo; Liao, Rong-xia

    2015-01-01

    Radiotherapy (RT) is a key therapeutic strategy for lung cancer, the most common cause of cancer-related deaths worldwide, but radioresistance often occurs and leads to failure of RT. It is therefore important to clarify the mechanism underlying radioresistance in lung cancer. Cancer stem cells (CSCs) are considered the fundamental reason for radioresistance. MicroRNAs (miRNAs) have been regarded as important regulatory molecules of CSCs, carcinogenesis, and treatment response of cancers. It is crucial to clarify how regulation of miRNAs affects repair of DNA damage, redistribution, repopulation, reoxygenation, and radiosensitivity (5R) of lung cancer stem cells (LCSCs). A thorough understanding of the regulation of miRNAs affecting 5R of LCSCs has potential impact on identifying novel targets and thus may improve the efficacy of lung cancer radiotherapy. PMID:25815339

  18. Gossypol with methyltestosterone and ethinylestradiol male does not affect rat spermatogonial stem cell differentiation.

    PubMed

    Cui, G; Zheng, W; Sun, Y; Zhang, Q; Deng, X; Chen, X

    2007-01-01

    The purpose of this study was to investigate whether administration of the regimen of gossypol at 12 mg/kg/day combined with methyltestosterone at 20 mg/kg/day and ethinylestradiol at 100 microg/kg/day for a long term of twenty-four weeks could affect the existence and differentiation of rat spermatogonial stem cell. This was assessed by conducting TdT-mediated dUTP nick end-labeling detection, spermatogonial stem cell transplantation and fertility recovery evaluation. Our results showed that spontaneous apoptosis was observed in normal rats' testes from the control group with an apoptotic index (AI) average of 10.24+/-1.52. In the regimen-treated group, the predominant apoptotic cells were spermatocytes and spermatids in the seminiferous tubules. Spermatogonia were not apoptotic (AI averaged 113.42+/-13.24). Two to three months after transplantation of spermatogonial stem cells isolated from regimen-treated rats into recipient nude mice, elongated rat spermatids were identified in the seminiferous tubules of recipient nude mice. Six weeks after withdrawal of the administration, fertility of the regimen-treated rats was recovered compared with that of the control group. The number of litters produced by females mated with regimen-treated males averaged 9.88+/-0.166 matched 10.30+/-0.171 of control group and the litters of the first generation appeared to be normal. These results indicated that the administration of this regimen did not affect the existence and differentiation potential of spermatogonial stem cells of the regimen-treated rats.

  19. Autologous peripheral blood stem cell harvest: Collection efficiency and factors affecting it

    PubMed Central

    Tiwari, Aseem K.; Pandey, Prashant; Subbaraman, Harini; Bhargava, Rahul; Rawat, Ganesh; Madiraju, Shivani; Raina, Vimarsh; Bhargava, Richa

    2016-01-01

    Background: Harvest of hematopoietic progenitor cells via leukapheresis is being used increasingly for transplants in India. Adequate yield of cells per kilogram body weight of recipient is required for successful engraftment. Collection efficiency (CE) is an objective quality parameter used to assess the quality of leukapheresis program. In this study, we calculated the CE of the ComTec cell separator (Fresenius Kabi, Germany) using two different formulae (CE1 and CE2) and analyzed various patient and procedural factors, which may affect it. Materials and Methods: One hundred and one consecutive procedures in 77 autologous donors carried out over 3 years period were retrospectively reviewed. Various characteristics like gender, age, weight, disease status, hematocrit, preprocedure total leukocyte count, preprocedure CD34 positive (CD34+) cells count, preprocedure absolute CD34+ cell count and processed apheresis volume effect on CE were compared. CE for each procedure was calculated using two different formulae, and results were compared using statistical correlation and regression analysis. Results: The mean CE1 and CE2 was 41.2 and 49.1, respectively. CE2 appeared to be more accurate indicator of overall CE as it considered the impact of continued mobilization of stem cells during apheresis procedure, itself. Of all the factors affecting CE, preprocedure absolute CD34+ was the only independent factor affecting CE. Conclusion: The only factor affecting CE was preprocedure absolute CD34+ cells. Though the mean CE2 was higher than CE1, it was not statistically significant. PMID:27011680

  20. Polyphenolic composition of grape stem extracts affects antioxidant activity in endothelial and muscle cells.

    PubMed

    Goutzourelas, Nikolaos; Stagos, Dimitrios; Spanidis, Ypatios; Liosi, Maria; Apostolou, Anna; Priftis, Alexandros; Haroutounian, Serko; Spandidos, Demetrios A; Tsatsakis, Aristidis M; Kouretas, Demetrios

    2015-10-01

    The aim of the present study was the assessment of the antioxidant effects of polyphenolic extracts derived from the stems of three Greek grape varieties (Moshomayro, Mavrotragano and Mandilaria) in endothelial (EA.hy926) and muscle (C2C12) cells. We also investigated the effects of the polyphenolic composition on the antioxidant effects of the grape stem extracts. For this purpose, the endothelial and muscle cells were treated with low non-cytotoxic concentrations of the extracts for 24 h in order to assess the effects of the extracts on cellular redox status using oxidative stress biomarkers. The oxidative stress markers were thiobarbituric acid reactive substances (TBARS), protein carbonyl (CARB) levels, reactive oxygen species (ROS) levels and glutathione (GSH) levels. The results revealed that treatment of the EA.hy926 cells with Mandilaria extract significantly decreased the TBARS levels by 14.8% and the CARB levels by 25.9 %, while it increased the GSH levels by 15.8% compared to the controls. Moreover, treatment of the EA.hy926 cells with Mavrotragano extract significantly increased the GSH levels by 20.2%, while it significantly decreased the TBARS and CARB levels by 12.5% and 16.6%, respectively. Treatment of the C2C12 cells with Mandilaria extract significantly decreased the TBARS levels by 47.3 %, the CARB levels by 39.0 % and the ROS levels by 21.8%, while it increased the GSH levels by 22.6% compared to the controls. Moreover, treatment of the C2C12 cells with Mavrotragano significantly decreased the TBARS, CARB and ROS levels by 36.2%, 35.9% and 16.5%, respectively. In conclusion, to the best of our knowledgel, our results demonstrate for the first time that treatment with grape stem extracts at low concentrations improves the redox status of endothelial and muscle cells. Thus, grape stem extracts may be used for developing antioxidant food supplements or biofunctional foods. However, it was also found that the polyphenolic composition of grape stem

  1. Molecular mechanism of extrinsic factors affecting anti-aging of stem cells.

    PubMed

    Wong, Tzyy Yue; Solis, Mairim Alexandra; Chen, Ying-Hui; Huang, Lynn Ling-Huei

    2015-03-26

    Scientific evidence suggests that stem cells possess the anti-aging ability to self-renew and maintain differentiation potentials, and quiescent state. The objective of this review is to discuss the micro-environment where stem cells reside in vivo, the secreted factors to which stem cells are exposed, the hypoxic environment, and intracellular factors including genome stability, mitochondria integrity, epigenetic regulators, calorie restrictions, nutrients, and vitamin D. Secreted tumor growth factor-β and fibroblast growth factor-2 are reported to play a role in stem cell quiescence. Extracellular matrices may interact with caveolin-1, the lipid raft on cell membrane to regulate quiescence. N-cadherin, the adhesive protein on niche cells provides support for stem cells. The hypoxic micro-environment turns on hypoxia-inducible factor-1 to prevent mesenchymal stem cells aging through p16 and p21 down-regulation. Mitochondria express glucosephosphate isomerase to undergo glycolysis and prevent cellular aging. Epigenetic regulators such as p300, protein inhibitors of activated Stats and H19 help maintain stem cell quiescence. In addition, calorie restriction may lead to secretion of paracrines cyclic ADP-ribose by intestinal niche cells, which help maintain intestinal stem cells. In conclusion, it is crucial to understand the anti-aging phenomena of stem cells at the molecular level so that the key to solving the aging mystery may be unlocked.

  2. The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel

    PubMed Central

    Mahadik, B.P.; Haba, S. Pedron; Skertich, L.J.; Harley, B.A.C.

    2015-01-01

    Hematopoietic stem cells (HSCs) are a rare stem cell population found primarily in the bone marrow and responsible for the production of the body’s full complement of blood and immune cells. Used clinically to treat a range of hematopoietic disorders, there is a significant need to identify approaches to selectively expand their numbers ex vivo. Here we describe a methacrylamide-functionalized gelatin (GelMA) hydrogel for in vitro culture of primary murine HSCs. Stem cell factor (SCF) is a critical biomolecular component of native HSC niches in vivo and is used in large dosages in cell culture media for HSC expansion in vitro. We report a photochemistry based approach to covalently immobilize SCF within GelMA hydrogels via acrylate-functionalized polyethylene glycol (PEG) tethers. PEG-functionalized SCF retains the native bioactivity of SCF but can be stably incorporated and retained within the GelMA hydrogel over 7 days. Freshly-isolated murine HSCs cultured in GelMA hydrogels containing covalently-immobilized SCF showed reduced proliferation and improved selectivity for maintaining primitive HSCs. Comparatively, soluble SCF within the GelMA hydrogel network induced increased proliferation of differentiating hematopoietic cells. We used a microfluidic templating approach to create GelMA hydrogels containing gradients of immobilized SCF that locally direct HSC response. Together, we report a biomaterial platform to examine the effect of the local presentation of soluble vs. matrix-immobilized biomolecular signals on HSC expansion and lineage specification. This approach may be a critical component of a biomaterial-based artificial bone marrow to provide the correct sequence of niche signals to grow HSCs in the laboratory. PMID:26232879

  3. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    NASA Astrophysics Data System (ADS)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (sbnd NH2), carboxyl (sbnd COOH) and methyl (sbnd CH3), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (sbnd COOH and sbnd NH2) can absorb more proteins than these modified with more hydrophobic functional group (sbnd CH3). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the sbnd NH2 modified surfaces encourage osteogenic differentiation; the sbnd COOH modified surfaces promote cell adhesion and spreading and the sbnd CH3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  4. Donor age of human platelet lysate affects proliferation and differentiation of mesenchymal stem cells.

    PubMed

    Lohmann, Michael; Walenda, Gudrun; Hemeda, Hatim; Joussen, Sylvia; Drescher, Wolf; Jockenhoevel, Stefan; Hutschenreuter, Gabriele; Zenke, Martin; Wagner, Wolfgang

    2012-01-01

    The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1), but it was significantly higher with HPLs from younger donors (<35 years) as compared to older donors (>45 years). Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal). HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1) or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation.

  5. FMR1 epigenetic silencing commonly occurs in undifferentiated fragile X-affected embryonic stem cells.

    PubMed

    Avitzour, Michal; Mor-Shaked, Hagar; Yanovsky-Dagan, Shira; Aharoni, Shira; Altarescu, Gheona; Renbaum, Paul; Eldar-Geva, Talia; Schonberger, Oshrat; Levy-Lahad, Ephrat; Epsztejn-Litman, Silvina; Eiges, Rachel

    2014-11-11

    Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from epigenetic silencing of the X-linked FMR1 gene by a CGG expansion in its 5'-untranslated region. Taking advantage of a large set of FXS-affected human embryonic stem cell (HESC) lines and isogenic subclones derived from them, we show that FMR1 hypermethylation commonly occurs in the undifferentiated state (six of nine lines, ranging from 24% to 65%). In addition, we demonstrate that hypermethylation is tightly linked with FMR1 transcriptional inactivation in undifferentiated cells, coincides with loss of H3K4me2 and gain of H3K9me3, and is unrelated to CTCF binding. Taken together, these results demonstrate that FMR1 epigenetic gene silencing takes place in FXS HESCs and clearly highlights the importance of examining multiple cell lines when investigating FXS and most likely other epigenetically regulated diseases.

  6. Diet Does Not Affect Putative Mammary Epithelial Stem Cells in Pre-weaned Holstein Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Overfeeding prepubertal heifers can impair mammary epithelial growth and development, processes that depend on stem cells. In this study we evaluated effects of diet composition on putative bovine mammary epithelial stem cell populations using a 5-bromo-2-deoxyrudine (BrdU; a thymidine analog) label...

  7. Nanog RNA-binding proteins YBX1 and ILF3 affect pluripotency of embryonic stem cells.

    PubMed

    Guo, Chuanliang; Xue, Yan; Yang, Guanheng; Yin, Shang; Shi, Wansheng; Cheng, Yan; Yan, Xiaoshuang; Fan, Shuyue; Zhang, Huijun; Zeng, Fanyi

    2016-08-01

    Nanog is a well-known transcription factor that plays a fundamental role in stem cell self-renewal and the maintenance of their pluripotent cell identity. There remains a large data gap with respect to the spectrum of the key pluripotency transcription factors' interaction partners. Limited information is available concerning Nanog-associated RNA-binding proteins (RBPs), and the intrinsic protein-RNA interactions characteristic of the regulatory activities of Nanog. Herein, we used an improved affinity protocol to purify Nanog-interacting RBPs from mouse embryonic stem cells (ESCs), and 49 RBPs of Nanog were identified. Among them, the interaction of YBX1 and ILF3 with Nanog mRNA was further confirmed by in vitro assays, such as Western blot, RNA immunoprecipitation (RIP), and ex vivo methods, such as immunofluorescence staining and fluorescent in situ hybridization (FISH), MS2 in vivo biotin-tagged RNA affinity purification (MS2-BioTRAP). Interestingly, RNAi studies revealed that YBX1 and ILF3 positively affected the expression of Nanog and other pluripotency-related genes. Particularly, downregulation of YBX1 or ILF3 resulted in high expression of mesoderm markers. Thus, a reduction in the expression of YBX1 and ILF3 controls the expression of pluripotency-related genes in ESCs, suggesting their roles in further regulation of the pluripotent state of ESCs.

  8. Marrow-inspired matrix cues rapidly affect early fate decisions of hematopoietic stem and progenitor cells

    PubMed Central

    Choi, Ji Sun; Harley, Brendan A. C.

    2017-01-01

    Hematopoiesis is the physiological process where hematopoietic stem cells (HSCs) continuously generate the body’s complement of blood and immune cells within unique regions of the bone marrow termed niches. Although previous investigations have revealed gradients in cellular and extracellular matrix (ECM) content across the marrow, and matrix elasticity and ligand type are believed to be strong regulators of stem cell fate, the impact of biophysical signals on HSC response is poorly understood. Using marrow-inspired ECM ligand–coated polyacrylamide substrates that present defined stiffness and matrix ligand cues, we demonstrate that the interplay between integrin engagement and myosin II activation processes affects the morphology, proliferation, and myeloid lineage specification of primary murine HSCs within 24 hours ex vivo. Notably, the impact of discrete biophysical signals on HSC fate decisions appears to be correlated to known microenvironmental transitions across the marrow. The combination of fibronectin and marrow matrix-associated stiffness was sufficient to maintain hematopoietic progenitor populations, whereas collagen and laminin enhanced proliferation and myeloid differentiation, respectively. Inhibiting myosin II–mediated contraction or adhesion to fibronectin via specific integrins (α5β1 and ανβ3) selectively abrogated the impact of the matrix environment on HSC fate decisions. Together, these findings indicate that adhesive interactions and matrix biophysical properties are critical design considerations in the development of biomaterials to direct HSC behavior in vitro. PMID:28070554

  9. Age affects gene expression in mouse spermatogonial stem/progenitor cells.

    PubMed

    Kokkinaki, Maria; Lee, Tin-Lap; He, Zuping; Jiang, Jiji; Golestaneh, Nady; Hofmann, Marie-Claude; Chan, Wai-Yee; Dym, Martin

    2010-06-01

    Spermatogenesis in man starts with spermatogonial stem cells (SSCs), and leads to the production of sperm in approximately 64 days, common to old and young men. Sperm from elderly men are functional and able to fertilize eggs and produce offspring, even though daily sperm production is more than 50% lower and damage to sperm DNA is significantly higher in older men than in those who are younger. Our hypothesis is that the SSC/spermatogonial progenitors themselves age. To test this hypothesis, we studied the gene expression profile of mouse SSC/progenitor cells at several ages using microarrays. After sequential enzyme dispersion, we purified the SSC/progenitors with immunomagnetic cell sorting using an antibody to GFRA1, a known SSC/progenitor cell marker. RNA was isolated and used for the in vitro synthesis of amplified and labeled cRNAs that were hybridized to the Affymetrix mouse genome microarrays. The experiments were repeated twice with different cell preparations, and statistically significant results are presented. Quantitative RT-PCR analysis was used to confirm the microarray results. Comparison of four age groups (6 days, 21 days, 60 days, and 8 months old) showed a number of genes that were expressed specifically in the older mice. Two of them (i.e. Icam1 and Selp) have also been shown to mark aging hematopoietic stem cells. On the other hand, the expression levels of the genes encoding the SSC markers Gfra1 and Plzf did not seem to be significantly altered by age, indicating that age affects only certain SSC/progenitor properties.

  10. Acute ethanol exposure affects spermatogonial stem cell homeostasis in pre-pubertal mice.

    PubMed

    Caires, Kyle C; Shima, Christina M; de Avila, Jeanene; McLean, Derek J

    2012-01-01

    Ethanol is a known modulator of neural stem cell development, but the consequences of ethanol toxicity on the cell fate decisions of spermatogonial stem cells (SSCs) is poorly understood. Using an in vivo treatment and stem cell transplantation approach, we investigated the effects of acute ethanol exposure on formation of the growing adult SSC population in neonatal and pre-pubertal mice. Treatment with a single dose of ethanol disrupted SSC homeostasis in vivo evidenced by a significant reduction (7-fold) of stem cell colonization efficiency in the testes of recipient mice following transplantation. Ethanol treatment also increased the rate of apoptosis in adult differentiating germ cells in situ. Gene expression analysis indicates that ethanol exposure has transient and long-term effects on the expression of GDNF and VEGF family molecules and supports the hypothesis that the niche microenvironment for SSCs is sensitive to ethanol toxicity during pre-pubertaland adult life.

  11. Proliferation of mouse embryonic stem cell progeny and the spontaneous contractile activity of cardiomyocytes are affected by microtopography.

    PubMed

    Biehl, Jesse K; Yamanaka, Satoshi; Desai, Tejal A; Boheler, Kenneth R; Russell, Brenda

    2009-08-01

    The niche in which stem cells reside and differentiate is a complex physicochemical microenvironment that regulates cell function. The role played by three-dimensional physical contours was studied on cell progeny derived from mouse embryonic stem cells using microtopographies created on PDMS (poly-dimethyl-siloxane) membranes. While markers of differentiation were not affected, the proliferation of heterogeneous mouse embryonic stem cell-derived progeny was attenuated by 15 microm-, but not 5 microm-high microprojections. This reduction was reversed by Rho kinase and myosin light chain kinase inhibition, which diminishes the tension generating ability of stress fibers. Purified cardiomyocytes derived from embryonic stem cells also showed significant blunting of proliferation and increased beating rates compared with cells grown on flat substrates. Thus, proliferation of stem cell-derived progeny appears to be regulated by microtopography through tension-generation of contractility in the third-dimension. These results emphasize the importance of topographic cues in the modulation of stem cell progeny behavior.

  12. Static stretch affects neural stem cell differentiation in an extracellular matrix-dependent manner

    PubMed Central

    Arulmoli, Janahan; Pathak, Medha M.; McDonnell, Lisa P.; Nourse, Jamison L.; Tombola, Francesco; Earthman, James C.; Flanagan, Lisa A.

    2015-01-01

    Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types of mechanical stimuli, such as stretch (tensile strain), occur during CNS development and trauma, but their consequences for NSPC differentiation have not been reported. We delivered a 10% static equibiaxial stretch to NSPCs and examined effects on differentiation. We found static stretch specifically impacts NSPC differentiation into oligodendrocytes, but not neurons or astrocytes, and this effect is dependent on particular extracellular matrix (ECM)-integrin linkages. Generation of oligodendrocytes from NSPCs was reduced on laminin, an outcome likely mediated by the α6 laminin-binding integrin, whereas similar effects were not observed for NSPCs on fibronectin. Our data demonstrate a direct role for tensile strain in dictating the lineage choice of NSPCs and indicate the dependence of this phenomenon on specific substrate materials, which should be taken into account for the design of biomaterials for NSPC transplantation. PMID:25686615

  13. Static stretch affects neural stem cell differentiation in an extracellular matrix-dependent manner

    NASA Astrophysics Data System (ADS)

    Arulmoli, Janahan; Pathak, Medha M.; McDonnell, Lisa P.; Nourse, Jamison L.; Tombola, Francesco; Earthman, James C.; Flanagan, Lisa A.

    2015-02-01

    Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types of mechanical stimuli, such as stretch (tensile strain), occur during CNS development and trauma, but their consequences for NSPC differentiation have not been reported. We delivered a 10% static equibiaxial stretch to NSPCs and examined effects on differentiation. We found static stretch specifically impacts NSPC differentiation into oligodendrocytes, but not neurons or astrocytes, and this effect is dependent on particular extracellular matrix (ECM)-integrin linkages. Generation of oligodendrocytes from NSPCs was reduced on laminin, an outcome likely mediated by the α6 laminin-binding integrin, whereas similar effects were not observed for NSPCs on fibronectin. Our data demonstrate a direct role for tensile strain in dictating the lineage choice of NSPCs and indicate the dependence of this phenomenon on specific substrate materials, which should be taken into account for the design of biomaterials for NSPC transplantation.

  14. Tributyltin affects adipogenic cell fate commitment in mesenchymal stem cells by a PPARγ independent mechanism.

    PubMed

    Biemann, Ronald; Fischer, Bernd; Blüher, Matthias; Navarrete Santos, Anne

    2014-05-05

    The food contaminant tributyltin (TBT) is an endocrine disrupting compound (EDC) promoting adipogenic differentiation in vitro and in vivo. Although prenatal TBT exposure has been shown to induce obesity, the underlying mechanisms and the role of the transcription factor PPARγ are not clarified yet. At different stages of adipogenesis, multipotent murine mesenchymal stem cells (MSC), C3H10T1/2, were exposed to TBT and analyzed for adipogenic differentiation, PPARγ promoter activation and PPARγ1, PPARγ2, Pref-1 and SOX9 expression. Depending on the exposure window, TBT promoted subsequent adipogenesis independently and dependently from PPARγ. In undifferentiated MSC, TBT exposure induced a transcriptional PPARγ-independent repression of Pref-1 and SOX9, which are both suppressors of adipogenic cell fate commitment. During hormonal induction TBT additionally enhanced adipogenic differentiation by PPARγ signaling. The impact of TBT on early cell fate development documents a novel mechanistic insight in the development of adipocytes derived from MSC and its susceptibility to EDC.

  15. The conflict between cell proliferation and expansion primarily affects stem organogenesis in Arabidopsis.

    PubMed

    Maeda, Saori; Gunji, Shizuka; Hanai, Kenya; Hirano, Tomonari; Kazama, Yusuke; Ohbayashi, Iwai; Abe, Tomoko; Sawa, Shinichiro; Tsukaya, Hirokazu; Ferjani, Ali

    2014-11-01

    Plant shoot organs such as stems, leaves and flowers are derived from specialized groups of stem cells organized at the shoot apical meristem (SAM). Organogenesis involves two major processes, namely cell proliferation and differentiation, whereby the former contributes to increasing the cell number and the latter involves substantial increases in cell volume through cell expansion. Co-ordination between the above processes in time and space is essential for proper organogenesis. To identify regulatory factors involved in proper organogenesis, heavy-ion beam-irradiated de-etiolated (det) 3-1 seeds have been used to identify striking phenotypes in the A#26-2; det3-1 mutant. In addition to the stunted plant stature mimicking det3-1, the A#26-2; det3-1 mutant exhibited stem thickening, increased floral organ number and a fruit shape reminiscent of clavata (clv) mutants. DNA sequencing analysis demonstrated that A#26-2; det3-1 harbors a mutation in the CLV3 gene. Importantly, A#26-2; det3-1 displayed cracks that randomly occurred on the main stem with a frequency of approximately 50%. Furthermore, the double mutants clv3-8 det3-1, clv1-4 det3-1 and clv2-1 det3-1 consistently showed stem cracks with frequencies of approximately 97, 38 and 35%, respectively. Cross-sections of stems further revealed an increase in vascular bundle number, cell number and size in the pith of clv3-8 det3-1 compared with det3-1. These findings suggest that the stem inner volume increase due to clv mutations exerts an outward mechanical stress; that in a det3-1 background (defective in cell expansion) resulted in cracking of the outermost layer of epidermal cells.

  16. Stem Cell Information: Glossary

    MedlinePlus

    ... cells (skeletal stem cells) Cell-based therapies Cell culture Cell division Chromosome Clone Cloning Cord blood stem cells Culture medium Differentiation Directed differentiation DNA Ectoderm Embryo Embryoid ...

  17. Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose.

    PubMed

    Jia, De-yong; Liu, Hui-juan; Wang, Fu-wu; Liu, Shang-ming; Ling, Eng-Ang; Liu, Kai; Hao, Ai-jun

    2008-07-25

    Folic acid (FA) supplementation has been shown to be extremely effective in reducing the occurrence of neural tube defects (NTDs), one of the most common birth defects associated with diabetic pregnancy. However, the antiteratogenic mechanism of FA in diabetes-induced NTDs is unclear. This study investigated the neuroprotective mechanism of FA in neural stem cells (NSCs) exposed to high glucose in vitro. The undifferentiated or differentiated NSCs were cultured in normal D-glucose concentration (NG) or high D-glucose concentration (HG) with or without FA. FA supplementation significantly decreased apoptosis induced by HG and lowered the expression of p53 in the nucleus of undifferentiated NSCs exposed to HG. Administration of FA in differentiated NSCs did not alter their precocious differentiation induced by HG. The increased mRNA expression levels of the basic helix-loop-helix factors including Neurog1, Neurog2, NeuroD2, Mash1, Id1, Id2, and Hes5 in the presence of HG were not significantly affected by FA. The present results provided a cellular mechanism by which FA supplementation may have a potential role in prevention of NTDs in diabetic pregnancies. On the other hand, FA increased the mRNA expression levels of the above transcription factors and accelerated the differentiation of NSCs in the NG medium, suggesting that it may adversely affect the normal differentiation of NSCs. Therefore, the timing and dose of FA would be critical factors in considering FA supplementation in normal maternal pregnancy.

  18. Therapeutic potential of mesenchymal stem cells in acute kidney injury is affected by administration timing.

    PubMed

    Liu, Xiaoyan; Cai, Jieru; Jiao, Xiaoyan; Yu, Xiaofang; Ding, Xiaoqiang

    2017-03-10

    Mesenchymal stem cell (MSC) transplantation is a promising therapy for acute kidney injury; however, the efficacy is limited due to poor survival after transplantation. In this study, we investigated how MSC transplantation timing affected the survival and therapeutic potential of MSCs in the kidney ischemia-reperfusion (I/R) injury model. After kidney I/R injury, the inflammatory process and tissue damage were characterized over 1 week post-I/R, we found that inflammation peaked at 12-24 h post-I/R (h.p.i.), and urine  neutrophil gelatinase-associated lipocalin (NGAL) measurements correlated highly with measures of inflammation. We cultured MSCs with supernatants from I/R injured kidney tissue homogenates collected at different time points and found that kidney homogenates from 12 and 24 h.p.i. were most toxic to MSCs, whereas homogenates from 1 h.p.i. were not as cytotoxic as those from 12 and 24 h.p.i. Compared with MSCs administered at 12, or 24 h.p.i., cells administered immediately after ischemia or 1 h.p.i. yielded the highest renoprotective and anti-inflammatory effects. Our findings indicate that MSC treatment for acute kidney injury is most effective when applied prior to the development of a potent inflammatory microenvironment, and urine NGAL may be helpful for detecting inflammation and selecting MSC transplantation timing in I/R kidney injury.

  19. Stem Cell Basics

    MedlinePlus

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  20. Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by osteoinductive calcium phosphate ceramics.

    PubMed

    Tang, Zhurong; Wang, Zhe; Qing, Fangzhu; Ni, Yilu; Fan, Yujiang; Tan, Yanfei; Zhang, Xingdong

    2015-03-01

    Porous calcium phosphate ceramics (CaP ceramics) could induce ectopic bone formation which was regulated by various signal molecules. In this work, bone marrow mesenchymal stem cells (MSCs) were cultured on the surface of osteoinductive hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramics in comparison with control (culture plate) for up to 14 days to detect the signal molecules which might be affected by the CaP ceramics. Without adding osteogenic factors, MSCs cultured on HA and BCP both expressed higher Runx2, Osterix, collagen type I, osteopontin, bone sialoprotein, and osteocalcin at various stages compared with control, thus confirmed the osteoblastic differentiation of MSCs. Later study demonstrated the messenger RNA level of bone morphogenetic protein 2 (BMP2) and BMP4 were also significantly enhanced by HA and BCP. Furthermore, Smad1, 4, 5, and Dlx5, the main molecules in the BMP/Smads signaling pathway, were upregulated by HA and BCP. Moreover, the higher expression of Smads and BMP2, 4 in BCP over HA, corresponded to the better performance of BCP in stimulating in vitro osteoblastic differentiation of MSCs. This was in accordance with the better osteoinductivity of BCP over HA in vivo. Altogether, these results implied that the CaP ceramics may initiate the osteoblastic differentiation of MSCs by influencing the expression of molecules in BMP/Smads pathway.

  1. Dietary calcium restriction affects mesenchymal stem cell activity and bone development in neonatal pigs.

    PubMed

    Mahajan, Avanika; Alexander, Lindsey S; Seabolt, Brynn S; Catrambone, Daniel E; McClung, James P; Odle, Jack; Pfeiler, T Wayne; Loboa, Elizabeth G; Stahl, Chad H

    2011-03-01

    The effects of dietary calcium (Ca) deficiency on skeletal integrity are well characterized in growing and mature mammals; however, less is known about Ca nutrition during the neonatal period. In this study, we examined the effects of neonatal Ca nutrition on bone integrity, endocrine hormones, and mesenchymal stem cell (MSC) activity. Neonatal pigs (24 ± 6 h of age) received either a Ca-adequate (1.2 g/100 g) or an ~40% Ca-deficient diet for 18 d. Ca deficiency reduced (P < 0.05) bone flexural strength and bone mineral density without major differences in plasma indicators of Ca status. There were no meaningful differences in plasma Ca, phosphate (PO(4)), parathyroid hormone, or 1,25-dihydroxycholecalciferol due to Ca nutrition throughout the study. Calcium deficiency also reduced (P < 0.05) the in vivo proliferation of MSC by ~50%. In vitro studies utilizing homologous sera demonstrated that MSC activity was affected (P < 0.05) by both the Ca status of the pig and the sera as well as by their interaction. The results indicate that neonatal Ca nutrition is crucial for bone integrity and suggest that early-life Ca restriction may have long-term effects on bone integrity via programming of MSC.

  2. Comparison of Periodontal Ligament Stem Cells Isolated from the Periodontium of Healthy Teeth and Periodontitis-Affected Teeth

    PubMed Central

    Soheilifar, Sara; Amiri, Iraj; Bidgoli, Mohsen; Hedayatipanah, Morad

    2016-01-01

    Objectives: Stem cell (SC) therapy is a promising technique for tissue regeneration. This study aimed to compare the viability and proliferation ability of periodontal ligament stem cells (PDLSCs) isolated from the periodontium of healthy and periodontitis-affected teeth to obtain an autologous, easily accessible source of SCs for tissue regeneration in periodontitis patients. Materials and Methods: The PDLSCs were isolated from the roots of clinically healthy premolars extracted for orthodontic purposes and periodontally involved teeth with hopeless prognosis (with and without phase I periodontal treatment). Cells were cultured and viability and proliferation ability of third passage cells in each group were evaluated using the methyl thiazol tetrazolium assay. The results were statistically analyzed using t-test. Results: No SCs could be obtained from periodontitis-affected teeth without phase I periodontal treatment. The viability of cells was 0.86±0.13 OD/540 in healthy group and 0.4±0.25 OD/540 in periodontitis-affected group (P=0.035). The proliferation ability (population doubling time) of cells obtained from healthy teeth was 4.22±1.23 hours. This value was 2.3±0.35 hours for those obtained from periodontitis-affected teeth (P=0.02). Conclusions: Viability and proliferation ability of cells isolated from the periodontium of healthy teeth were significantly greater than those of cells isolated from the periodontitis-affected teeth. PMID:28127319

  3. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1-60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  4. Derivation of Huntington Disease affected Genea091 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea091 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 98% SSEA4 and gave a Pluritest pluripotency score of 38.36, Novelty of 1.35. The cell line was negative for Mycoplasma and visible contamination.

  5. Derivation of Huntington Disease affected Genea089 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea089 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 41 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a PluriTest Pluripotency score of 39.28, Novelty of 1.2. The cell line was negative for Mycoplasma and visible contamination.

  6. Derivation of Huntington disease affected Genea020 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Peura, Teija; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1.43 and demonstrated alkaline phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  7. Derivation of Huntington Disease affected Genea018 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea018 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 46 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 75% of cells expressed Nanog, 91% Oct4, 73% Tra1-60 and 96% SSEA4, gave a Pluritest pluripotency score of 31.12, Novelty of 1.45, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.

  8. Methanolic extracts of bitter melon inhibit colon cancer stem cells by affecting energy homeostasis and autophagy.

    PubMed

    Kwatra, Deep; Subramaniam, Dharmalingam; Ramamoorthy, Prabhu; Standing, David; Moran, Elizabeth; Velayutham, Ravichandiran; Mitra, Ashim; Umar, Shahid; Anant, Shrikant

    2013-01-01

    Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit (BMW) and skin (BMSk) extracts showed significant inhibition of cell proliferation and colony formation, with BMW showing greater efficacy. In addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were undergoing autophagy and not apoptosis. Further confirmation of autophagy was obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7 and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with activation of AMP activated protein kinase; on the other hand, exogenous additions of ATP lead to revival of cell proliferation. Finally, BMW treatment results in a dose-dependent reduction in the number and size of colonospheres. The extracts also decreased the expression of DCLK1 and Lgr5, markers of quiescent, and activated stem cells. Taken together, these results suggest that the extracts of bitter melon can be an effective preventive/therapeutic agent for colon cancer.

  9. Generation of Human Induced Pluripotent Stem Cells from Extraembryonic Tissues of Fetuses Affected by Monogenic Diseases.

    PubMed

    Spitalieri, Paola; Talarico, Rosa V; Botta, Annalisa; Murdocca, Michela; D'Apice, Maria Rosaria; Orlandi, Augusto; Giardina, Emiliano; Santoro, Massimo; Brancati, Francesco; Novelli, Giuseppe; Sangiuolo, Federica

    2015-08-01

    The generation of human induced pluripotent stem cells (hiPSCs) derived from an autologous extraembryonic fetal source is an innovative personalized regenerative technology that can transform own-self cells into embryonic stem-like ones. These cells are regarded as a promising candidate for cell-based therapy, as well as an ideal target for disease modeling and drug discovery. Thus, hiPSCs enable researchers to undertake studies for treating diseases or for future applications of in utero therapy. We used a polycistronic lentiviral vector (hSTEMCCA-loxP) encoding OCT4, SOX2, KLF4, and cMYC genes and containing loxP sites, excisible by Cre recombinase, to reprogram patient-specific fetal cells derived from prenatal diagnosis for several genetic disorders, such as myotonic dystrophy type 1 (DM1), β-thalassemia (β-Thal), lymphedema-distichiasis syndrome (LDS), spinal muscular atrophy (SMA), cystic fibrosis (CF), as well as from wild-type (WT) fetal cells. Because cell types tested to create hiPSCs influence both the reprogramming process efficiency and the kinetics, we used chorionic villus (CV) and amniotic fluid (AF) cells, demonstrating how they represent an ideal cell resource for a more efficient generation of hiPSCs. The successful reprogramming of both CV and AF cells into hiPSCs was confirmed by specific morphological, molecular, and immunocytochemical markers and also by their teratogenic potential when inoculated in vivo. We further demonstrated the stability of reprogrammed cells over 10 and more passages and their capability to differentiate into the three embryonic germ layers, as well as into neural cells. These data suggest that hiPSCs-CV/AF can be considered a valid cellular model to accomplish pathogenesis studies and therapeutic applications.

  10. Derivation of Huntington Disease affected Genea017 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea017 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1.27, demonstrated alkaline phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.

  11. Derivation of FSHD1 affected human embryonic stem cell line Genea049.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea049 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 5 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 90% of cells expressed Nanog, 96% Oct4, 80% Tra1-60 and 99% SSEA4, gave a Pluritest Pluripotency score of 23.16, Novelty of 1.43 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  12. JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

    SciTech Connect

    Das, Amitabh; Chai, Jin Choul; Jung, Kyoung Hwa; Das, Nando Dulal; Kang, Sung Chul; Lee, Young Seek; Seo, Hyemyung; Chai, Young Gyu

    2014-11-01

    JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53{sup −/−} NE-4Cs). We determined the effect of LPS as a model of inflammation in p53{sup −/−} NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53{sup −/−} NE-4Cs and in LPS-stimulated JMJD2A-kd p53{sup −/−} NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. - Highlights: • Significant up-regulation of epigenetic modifier JMJD2A mRNA upon LPS treatment. • Inhibition of JMJD2A attenuated key inflammatory and tumourigenic genes. • Establishing IPA based functional genomics in JMJD2A-attenuated p53{sup

  13. Stem Cell Sciences plc.

    PubMed

    Daniels, Sebnem

    2006-09-01

    Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

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

    SciTech Connect

    Rauner, Gat; Barash, Itamar

    2014-10-15

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

  15. Measuring stem cell circadian rhythm.

    PubMed

    Hrushesky, William; Rich, Ivan N

    2015-01-01

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

  16. The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation

    PubMed Central

    Isernhagen, Antje; Malzahn, Dörthe; Viktorova, Elena; Elsner, Leslie; Monecke, Sebastian; von Bonin, Frederike; Kilisch, Markus; Wermuth, Janne Marieke; Walther, Neele; Balavarca, Yesilda; Stahl-Hennig, Christiane; Engelke, Michael; Walter, Lutz; Bickeböller, Heike; Kube, Dieter; Wulf, Gerald; Dressel, Ralf

    2015-01-01

    The MHC class I chain-related molecule A (MICA) is a highly polymorphic ligand for the activating natural killer (NK)-cell receptor NKG2D. A single nucleotide polymorphism causes a valine to methionine exchange at position 129. Presence of a MICA-129Met allele in patients (n = 452) undergoing hematopoietic stem cell transplantation (HSCT) increased the chance of overall survival (hazard ratio [HR] = 0.77, P = 0.0445) and reduced the risk to die due to acute graft-versus-host disease (aGVHD) (odds ratio [OR] = 0.57, P = 0.0400) although homozygous carriers had an increased risk to experience this complication (OR = 1.92, P = 0.0371). Overall survival of MICA-129Val/Val genotype carriers was improved when treated with anti-thymocyte globulin (HR = 0.54, P = 0.0166). Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon-γ release, and faster co-stimulation of CD8+ T cells. The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8+ T cells than the MICA-129Val isoform. The reduced cell surface expression of NKG2D in response to engagement by MICA-129Met variants appeared to reduce the severity of aGVHD. PMID:26483398

  17. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  18. Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPARγ Expression and Activation in Differentiating Mesenchymal Stem Cells

    PubMed Central

    Rivas, Daniel; Akter, Rahima; Duque, Gustavo

    2007-01-01

    Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPARγ2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPARγ, and SREBP-1 were determined by western blot. Finally, DNA binding PPARγ activity was determined using an ELISA-based PPARγ activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPARγ expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPARγ activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPARγ expression and activity. PMID:18274630

  19. Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPARgamma Expression and Activation in Differentiating Mesenchymal Stem Cells.

    PubMed

    Rivas, Daniel; Akter, Rahima; Duque, Gustavo

    2007-01-01

    Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPARgamma2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPARgamma, and SREBP-1 were determined by western blot. Finally, DNA binding PPARgamma activity was determined using an ELISA-based PPARgamma activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPARgamma expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPARgamma activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPARgamma expression and activity.

  20. FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons

    PubMed Central

    Errichelli, Lorenzo; Dini Modigliani, Stefano; Laneve, Pietro; Colantoni, Alessio; Legnini, Ivano; Capauto, Davide; Rosa, Alessandro; De Santis, Riccardo; Scarfò, Rebecca; Peruzzi, Giovanna; Lu, Lei; Caffarelli, Elisa; Shneider, Neil A.; Morlando, Mariangela; Bozzoni, Irene

    2017-01-01

    The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUSP525L mutation associated with ALS. PMID:28358055

  1. FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons.

    PubMed

    Errichelli, Lorenzo; Dini Modigliani, Stefano; Laneve, Pietro; Colantoni, Alessio; Legnini, Ivano; Capauto, Davide; Rosa, Alessandro; De Santis, Riccardo; Scarfò, Rebecca; Peruzzi, Giovanna; Lu, Lei; Caffarelli, Elisa; Shneider, Neil A; Morlando, Mariangela; Bozzoni, Irene

    2017-03-30

    The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUS(P525L) mutation associated with ALS.

  2. The Tumorigenicity of Multipotent Adult Germline Stem Cells Transplanted into the Heart Is Affected by Natural Killer Cells and by Cyclosporine A Independent of Its Immunosuppressive Effects

    PubMed Central

    Hübscher, Daniela; Kaiser, Diana; Elsner, Leslie; Monecke, Sebastian; Dressel, Ralf; Guan, Kaomei

    2017-01-01

    Transplantation of stem cells represents an upcoming therapy for many degenerative diseases. For clinical use, transplantation of pluripotent stem cell-derived cells should lead to integration of functional grafts without immune rejection or teratoma formation. Our previous studies showed that the risk of teratoma formation is highly influenced by the immune system of the recipients. In this study, we have observed a higher teratoma formation rate when undifferentiated so-called multipotent adult germline stem cells (maGSCs) were transplanted into the heart of T, B, and natural killer (NK) cell-deficient RAG2−/−γc−/− mice than in RAG2−/− mice, which still have NK cells. Notably, in both strains, the teratoma formation rate was significantly reduced by the immunosuppressive drug cyclosporine A (CsA). Thus, CsA had a profound effect on teratoma formation independent of its immunosuppressive effects. The transplantation into RAG2−/− mice led to an activation of NK cells, which reached the maximum 14 days after transplantation and was not affected by CsA. The in vivo-activated NK cells efficiently killed YAC-1 and also maGSC target cells. This NK cell activation was confirmed in C57BL/6 wild-type mice whether treated with CsA or not. Sham operations in wild-type mice indicated that the inflammatory response to open heart surgery rather than the transplantation of maGSCs activated the NK cell system. An activation of NK cells during the transplantation of stem cell-derived in vitro differentiated grafts might be clinically beneficial by reducing the risk of teratoma formation by residual pluripotent cells. PMID:28220117

  3. Liver cancer stem cells.

    PubMed

    Sell, Stewart; Leffert, Hyam L

    2008-06-10

    In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

  4. Sirtinol, a Sir2 protein inhibitor, affects stem cell maintenance and root development in Arabidopsis thaliana by modulating auxin-cytokinin signaling components

    PubMed Central

    Singh, Sharmila; Singh, Alka; Yadav, Sandeep; Gautam, Vibhav; Singh, Archita; Sarkar, Ananda K.

    2017-01-01

    In Arabidopsis thaliana, besides several key transcription factors and chromatin modifiers, phytohormones auxin and cytokinin play pivotal role in shoot and root meristem maintenance, and lateral root (LR) development. Sirtinol, a chemical inhibitor of Sir2 proteins, is known to promote some auxin induced phenotypes in Arabidopsis. However, its effect on plant stem cell maintenance or organ formation remained unaddressed. Here we show that sirtinol affects meristem maintenance by altering the expression of key stem cell regulators, cell division and differentiation by modulating both auxin and cytokinin signaling in Arabidopsis thaliana. The expression of shoot stem cell niche related genes WUSCHEL (WUS) and CLAVATA3 (CLV3) was upregulated, whereas SHOOT MERISTEMLESS (STM) was downregulated in sirtinol treated seedlings. The expression level and domain of key root stem cell regulators PLETHORA (PLTs) and WUS-Related Homeobox 5 (WOX5) were altered in sirtinol treated roots. Sirtinol affects LR development by disturbing proper auxin transport and maxima formation, similar to 2,4-dichlorophenoxyacetic acid (2,4-D). Sirtinol also affects LR formation by altering cytokinin biosynthesis and signaling genes in roots. Therefore, sirtinol affects shoot and root growth, meristem maintenance and LR development by altering the expression of cytokinin-auxin signaling components, and regulators of stem cells, meristems, and LRs. PMID:28195159

  5. Stem Cell Transplant

    MedlinePlus

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  6. Stem cell regulation: Implications when differentiated cells regulate symmetric stem cell division.

    PubMed

    Høyem, Marte Rørvik; Måløy, Frode; Jakobsen, Per; Brandsdal, Bjørn Olav

    2015-09-07

    We use a mathematical model to show that if symmetric stem cell division is regulated by differentiated cells, then changes in the population dynamics of the differentiated cells can lead to changes in the population dynamics of the stem cells. More precisely, the relative fitness of the stem cells can be affected by modifying the death rate of the differentiated cells. This result is interesting because stem cells are less sensitive than differentiated cells to environmental factors, such as medical therapy. Our result implies that stem cells can be manipulated indirectly by medical treatments that target the differentiated cells.

  7. Aging, metabolism and stem cells: Spotlight on muscle stem cells.

    PubMed

    García-Prat, Laura; Muñoz-Cánoves, Pura

    2017-04-15

    All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population.

  8. Plant stem cell niches.

    PubMed

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  9. Nail stem cells.

    PubMed

    Sellheyer, Klaus

    2013-03-01

    Our knowledge on stem cells of the hair follicle has increased exponentially after the bulge was characterized as the stem cell niche two decades ago. In contrast, little is known about stem cells in the nail unit. Whereas hair follicles are plentiful and easy to access, the human body has only twenty nails and they are rarely biopsied. Therefore, examining fetal material offers unique advantages. In the following mini-review, our current knowledge on nail stem cells is summarized and analogies to the hair follicle stem cells are drawn.

  10. Does the Harvesting Technique Affect the Properties of Adipose-Derived Stem Cells?-The Comparative Biological Characterization.

    PubMed

    Bajek, Anna; Gurtowska, Natalia; Olkowska, Joanna; Maj, Małgorzata; Kaźmierski, Łukasz; Bodnar, Magdalena; Marszałek, Andrzej; Dębski, Robert; Drewa, Tomasz

    2017-05-01

    The objective of this study was to evaluate complex biological properties of human stem cells isolated from adipose tissue (ASCs) harvested utilizing different methods: surgical resection (R), power-assisted liposuction (PAL), and laser-assisted liposuction (LAL). ASCs were isolated from healthy donors, due to surgical resection, power-, and laser-assisted liposuction. Isolated cells were characterized by their clonogenicity, proliferation rate, doubling time, multilineage differentiation, and senescence potential. The average number of ASCs from 1g/1 ml of solid adipose tissue/lipoaspirate was 2.9 × 10(5)  ± 2.4 × 10(5) , 1.1 × 10(5)  ± 0.8 × 10(5) , and 1.2 × 10(5)  ± 0.7 × 10(5) , respectively, for ASCsR, ASCsPAL, and ASCsLAL. However, number of colonies formed by ASCsR and ASCsPAL was significantly higher compared to the average number of colonies formed by ASCsLAL. Also, in comparison to other analyzed cell groups, ASCsPAL obtained the highest proliferative activity. All analyzed cells were characterized by stable expression of CD90 and CD44 markers during prolonged culture. Expression of CD34 and CD45 markers was decreasing in subsequent passages. Presented study shows that different ASCs collection method affects some basic characteristics of these cells, such as number of isolated cells, clonogeneity, or doubling time. J. Cell. Biochem. 118: 1097-1107, 2017. © 2016 Wiley Periodicals, Inc.

  11. Learn About Stem Cells

    MedlinePlus

    ... develops and ages, the number and type of stem cells changes. Totipotent cells are no longer present after dividing into the cells that generate the placenta and umbilical cord. Pluripotent cells ... organs and tissues. The stem cells that stay in your body throughout your ...

  12. Stem cell mitochondria during aging.

    PubMed

    Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Shyh-Chang, Ng

    2016-04-01

    Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future.

  13. Stress and stem cells.

    PubMed

    Tower, John

    2012-01-01

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

  14. Chemo-Predictive Assay for Targeting Cancer Stem-Like Cells in Patients Affected by Brain Tumors

    PubMed Central

    Nande, Rounak; Neto, Walter; Lawrence, Logan; McCallister, Danielle R.; Denvir, James; Kimmey, Gerrit A.; Mogul, Mark; Oakley, Gerard; Denning, Krista L.; Dougherty, Thomas; Valluri, Jagan V.; Claudio, Pier Paolo

    2014-01-01

    Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID), which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1) and a 5-month female (patient 2), affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC) greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity of CSLCs as

  15. Addition of plerixafor to mobilization regimens in autologous peripheral blood stem cell transplants does not affect the correlation of preharvest hematopoietic precursor cell enumeration with first-harvest CD34+ stem cell yield.

    PubMed

    Villa, Carlos H; Shore, Tsiporah; Van Besien, Koen; Cushing, Melissa

    2012-12-01

    The CXCR4 antagonist plerixafor is increasingly used in the mobilization regimens for autologous peripheral blood stem cell (PBSC) transplantation. This agent may mobilize a different subset of the stem cell population than traditional regimens, such as growth factors (with and without chemotherapy). Thus, it is important to determine whether plerixafor has an effect on the utility of measurements used to predict the yield of CD34(+) cells, usually either preharvest peripheral blood CD34(+) enumeration by flow cytometry or hematopoietic precursor cell (HPC) enumeration by automated hematology analysis. Although HPC enumeration has a weaker correlation with first-harvest CD34(+) cell yield, this parameter still plays an important role in the timing of apheresis procedures for autologous PBSC transplantation because of its technical simplicity and low cost. In the present study, we retrospectively examined the correlation of HPC measurements with CD34(+) cell yields in patients with multiple myeloma and lymphoma undergoing autologous PBSC transplantation, and investigated how the mobilization regimen affected these results. We found that the correlation coefficients ranged from 0.5877 to 0.7668 and were not significantly impacted by differences in diagnosis or inclusion of plerixafor in the mobilization regimen. The predictive ability of HPC enumeration for various target yields was also examined, and receiver-operating characteristic curves were generated. An HPC cutoff of 20 should result in adequate initial CD34(+) cell yields (>2.5 × 10(6) cell/kg) in >80% of autologous donors with or without plerixafor. This study confirms the utility of HPC enumeration in prediction of adequate initial cell yields, and demonstrates that this utility is maintained regardless of whether or not plerixafor is included in the mobilization regimen.

  16. Colorectal cancer stem cells.

    PubMed

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  17. Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments

    PubMed Central

    Barrachina, Laura; Remacha, Ana Rosa; Romero, Antonio; Vázquez, Francisco José; Albareda, Jorge; Prades, Marta; Ranera, Beatriz; Zaragoza, Pilar; Martín-Burriel, Inmaculada

    2017-01-01

    Mesenchymal stem cells (MSCs) are gaining relevance for treating equine joint injuries because of their ability to limit inflammation and stimulate regeneration. Because inflammation activates MSC immunoregulatory function, proinflammatory priming could improve MSC efficacy. However, inflammatory molecules present in synovial fluid or added to the culture medium might have deleterious effects on MSCs. Therefore, this study was conducted to investigate the effects of inflammatory synovial fluid and proinflammatory cytokines priming on viability and plasticity of equine MSCs. Equine bone marrow derived MSCs (eBM-MSCs) from three animals were cultured for 72 h in media supplemented with: 20% inflammatory synovial fluid (SF); 50 ng/mL IFN-γ and TNF-α (CK50); and 20 ng/mL IFN-γ and TNF-α (CK20). Proliferation assay and expression of proliferation and apoptosis-related genes showed that SF exposed-eBM-MSCs maintained their viability, whereas the viability of CK primed-eBM-MSCs was significantly impaired. Tri-lineage differentiation assay revealed that exposure to inflammatory synovial fluid did not alter eBM-MSCs differentiation potential; however, eBM-MSCs primed with cytokines did not display osteogenic, adipogenic or chondrogenic phenotype. The inflammatory synovial environment is well tolerated by eBM-MSCs, whereas cytokine priming negatively affects the viability and differentiation abilities of eBM-MSCs, which might limit their in vivo efficacy. PMID:27297420

  18. Collagen Substrate Stiffness Anisotropy Affects Cellular Elongation, Nuclear Shape, and Stem Cell Fate toward Anisotropic Tissue Lineage.

    PubMed

    Islam, Anowarul; Younesi, Mousa; Mbimba, Thomas; Akkus, Ozan

    2016-09-01

    Rigidity of substrates plays an important role in stem cell fate. Studies are commonly carried out on isotropically stiff substrate or substrates with unidirectional stiffness gradients. However, many native tissues are anisotropically stiff and it is unknown whether controlled presentation of stiff and compliant material axes on the same substrate governs cytoskeletal and nuclear morphology, as well as stem cell differentiation. In this study, electrocompacted collagen sheets are stretched to varying degrees to tune the stiffness anisotropy (SA) in the range of 1 to 8, resulting in stiff and compliant material axes orthogonal to each other. The cytoskeletal aspect ratio increased with increasing SA by about fourfold. Such elongation was absent on cellulose acetate replicas of aligned collagen surfaces indicating that the elongation was not driven by surface topography. Mesenchymal stem cells (MSCs) seeded on varying anisotropy sheets displayed a dose-dependent upregulation of tendon-related markers such as Mohawk and Scleraxis. After 21 d of culture, highly anisotropic sheets induced greater levels of production of type-I, type-III collagen, and thrombospondin-4. Therefore, SA has direct effects on MSC differentiation. These findings may also have ramifications of stem cell fate on other anisotropically stiff tissues, such as skeletal/cardiac muscles, ligaments, and bone.

  19. Developmental exposure to T-2 toxin reversibly affects postnatal hippocampal neurogenesis and reduces neural stem cells and progenitor cells in mice.

    PubMed

    Tanaka, Takeshi; Abe, Hajime; Kimura, Masayuki; Onda, Nobuhiko; Mizukami, Sayaka; Yoshida, Toshinori; Shibutani, Makoto

    2016-08-01

    To determine the developmental exposure effects of T-2 toxin on postnatal hippocampal neurogenesis, pregnant ICR mice were provided a diet containing T-2 toxin at 0, 1, 3, or 9 ppm from gestation day 6 to day 21 on weaning after delivery. Offspring were maintained through postnatal day (PND) 77 without T-2 toxin exposure. In the hippocampal dentate gyrus of male PND 21 offspring, GFAP(+) and BLBP(+) type-1 stem cells and PAX6(+) and TBR2(+) type-2 progenitor cells decreased in the subgranular zone (SGZ) at 9 and ≥3 ppm, respectively, in parallel with increased apoptosis at ≥3 ppm. In the dentate hilus, reelin(+) γ-aminobutyric acid (GABA)-ergic interneurons increased at 9 ppm, suggesting reflection of neuronal mismigration. T-2 toxin decreased transcript levels of cholinergic and glutamate receptor subunits (Chrna4, Chrnb2 and Gria2) and glutamate transporter (Slc17a6) in the dentate gyrus, suggesting decreased cholinergic signals on hilar GABAergic interneurons innervating type-2 cells and decreased glutamatergic signals on type-1 and type-2 cells. T-2 toxin decreased SGZ cells expressing stem cell factor (SCF) and increased cells accumulating malondialdehydes. Neurogenesis-related changes disappeared on PND 77, suggesting that T-2 toxin reversibly affects neurogenesis by inducing apoptosis of type-1 and type-2 cells with different threshold levels. Decreased cholinergic and glutamatergic signals may decrease type-2 cells at ≥3 ppm. Additionally, decreased SCF/c-Kit interactions and increased oxidative stress may decrease type-1 and type-2 cells at 9 ppm. The no-observed-adverse-effect level for offspring neurogenesis was determined to be 1 ppm (0.14-0.49 mg/kg body weight/day).

  20. Intraoperative Stem Cell Therapy

    PubMed Central

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

    2013-01-01

    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

  1. Co-precipitation of DEAE-dextran coated SPIONs: how synthesis conditions affect particle properties, stem cell labelling and MR contrast.

    PubMed

    Barrow, Michael; Taylor, Arthur; García Carrión, Jaime; Mandal, Pranab; Park, B Kevin; Poptani, Harish; Murray, Patricia; Rosseinsky, Matthew J; Adams, Dave J

    2016-09-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents for stem cell tracking using magnetic resonance imaging (MRI). The total mass of iron oxide that can be internalised into cells without altering their viability or phenotype is an important criterion for the generation of contrast, with SPIONs designed for efficient labelling of stem cells allowing for an increased sensitivity of detection. Although changes in the ratio of polymer and iron salts in co-precipitation reactions are known to affect the physicochemical properties of SPIONs, particularly core size, the effects of these synthesis conditions on stem cell labelling and magnetic resonance (MR) contrast have not been established. Here, we synthesised a series of cationic SPIONs with very similar hydrodynamic diameters and surface charges, but different polymer content. We have investigated how the amount of polymer in the co-precipitation reaction affects core size and modulates not only the magnetic properties of the SPIONs but also their uptake into stem cells. SPIONs with the largest core size and lowest polymer content presented the highest magnetisation and relaxivity. These particles also had the greatest uptake efficiency without any deleterious effect on either the viability or function of the stem cells. However, for all particles internalised in cells, the T2 and T2(*) relaxivity was independent of the SPION's core size. Our results indicate that the relative mass of iron taken up by cells is the major determinant of MR contrast generation and suggest that the extent of SPION uptake can be regulated by the amount of polymer used in co-precipitation reactions. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Myeloproliferative neoplasm stem cells.

    PubMed

    Mead, Adam J; Mullally, Ann

    2017-03-23

    Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC.

  3. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  4. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants A ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  5. ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential

    SciTech Connect

    Carcamo-Orive, Ivan; Tejados, Naiara; Delgado, Jesus; Gaztelumendi, Ainhoa; Otaegui, David; Lang, Valerie; Trigueros, Cesar

    2008-05-01

    Human Mesenchymal Stem Cells (hMSC), derived mainly from adult bone marrow, are valuable models for the study of processes involved in stem cell self-renewal and differentiation. As the Extracellular signal-Regulated Kinase (ERK) signalling pathway is a major contributor to cellular growth, differentiation and survival, we have studied the functions of this kinase in hMSC activity. Ablation of ERK2 gene expression (but not ERK1) by RNA interference significantly reduced proliferation of hMSC. This reduction was due to a defect in Cyclin D1 expression and subsequent arrest in the G0/G1 phase of the cell cycle. hMSC growth is enhanced through culture medium supplementation with growth factors (GFs) such as Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF) or Epidermal Growth Factor (EGF). However, these supplements could not rescue the defect observed after ERK2 knockdown, suggesting a common signalling pathway used by these GFs for proliferation. In contrast, ERK1/2 may be dissociated from chemotactic signalling induced by the same GFs. Additionally, hMSCs were capable of differentiating into adipocytes even in the absence of either ERK1 or ERK2 proteins. Our data show that hMSCs do not require cell division to enter the adipogenic differentiation process, indicating that clonal amplification of these cells is not a critical step. However, cell-cell contact seems to be an essential requirement to be able to differentiate into mature adipocytes.

  6. Stem cell strategies, future and beyond.

    PubMed

    Sugaya, Kiminobu

    2003-01-01

    The use of stem cells for neuroreplacement therapy is no longer science fiction--it is science fact. We have succeeded in the development of neural and mesenchymal stem cell transplantation to produce neural cells in the brain. We have seen the improvement of cognitive function in a memory-impaired aged animal model following stem cell transplantation. These results may promise a bright future for stem cell strategies. Before we begin to think about clinical applications beyond the present preclinical studies or even consider the pathophysiological environments of individual diseases, we must address and weigh the factors that may affect stem cell biology. Here, we not only show the potential for therapeutic applications for stem cell strategies in neuropathological conditions, but we also discuss the effects on the biology of stem cells of those factors that are altered under disease conditions.

  7. Hematopoietic Stem Cells Therapies.

    PubMed

    Chivu-Economescu, Mihaela; Rubach, Martin

    2017-01-01

    Stem cell-based therapies are recognized as a new way to treat various diseases and injuries, with a wide range of health benefits. The goal is to heal or replace diseased or destroyed organs or body parts with healthy new cells provided by stem cell transplantation. The current practical form of stem cell therapy is the hematopoietic stem cells transplant applied for the treatment of hematological disorders. There are over 2100 clinical studies in progress concerning hematopoietic stem cell therapies. All of them are using hematopoietic stem cells to treat various diseases like: cancers, leukemia, lymphoma, cardiac failure, neural disorders, auto-immune diseases, immunodeficiency, metabolic or genetic disorders. Several challenges are to be addressed prior to developing and applying large scale cell therapies: 1) to explain and control the mechanisms of differentiation and development toward a specific cell type needed to treat the disease, 2) to obtain a sufficient number of desired cell type for transplantation, 3) to overcome the immune rejection and 4) to show that transplanted cells fulfill their normal functions in vivo after transplants.

  8. Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors.

    PubMed

    Karamitros, Dimitris; Patmanidi, Alexandra L; Kotantaki, Panoraia; Potocnik, Alexandre J; Bähr-Ivacevic, Tomi; Benes, Vladimir; Lygerou, Zoi; Kioussis, Dimitris; Taraviras, Stavros

    2015-01-01

    Balancing stem cell self-renewal and initiation of lineage specification programs is essential for the development and homeostasis of the hematopoietic system. We have specifically ablated geminin in the developing murine hematopoietic system and observed profound defects in the generation of mature blood cells, leading to embryonic lethality. Hematopoietic stem cells (HSCs) accumulated in the fetal liver following geminin ablation, while committed progenitors were reduced. Genome-wide transcriptome analysis identified key HSC transcription factors as being upregulated upon geminin deletion, revealing a gene network linked with geminin that controls fetal hematopoiesis. In order to obtain mechanistic insight into the ability of geminin to regulate transcription, we examined Hoxa9 as an example of a key gene in definitive hematopoiesis. We demonstrate that in human K562 cells geminin is associated with HOXA9 regulatory elements and its absence increases HOXA9 transcription similarly to that observed in vivo. Moreover, silencing geminin reduced recruitment of the PRC2 component SUZ12 to the HOXA9 locus and resulted in an increase in RNA polymerase II recruitment and H3K4 trimethylation (H3K4me3), whereas the repressive marks H3K9me3 and H3K27me3 were reduced. The chromatin landscape was also modified at the regulatory regions of HOXA10 and GATA1. K562 cells showed a reduced ability to differentiate to erythrocytes and megakaryocytes upon geminin silencing. Our data suggest that geminin is indispensable for fetal hematopoiesis and regulates the generation of a physiological pool of stem and progenitor cells in the fetal hematopoietic system.

  9. Stem Cell Organoid Engineering

    PubMed Central

    Yin, Xiaolei; Mead, Benjamin E.; Safaee, Helia; Langer, Robert; Karp, Jeffrey M.; Levy, Oren

    2016-01-01

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies. PMID:26748754

  10. Engineering Stem Cell Organoids.

    PubMed

    Yin, Xiaolei; Mead, Benjamin E; Safaee, Helia; Langer, Robert; Karp, Jeffrey M; Levy, Oren

    2016-01-07

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies.

  11. [On plant stem cells and animal stem cells].

    PubMed

    You, Yun; Jiang, Chao; Huang, Lu-Qi

    2014-01-01

    A comparison of plant and animal stem cells can highlight core aspects of stem-cell biology. In both kingdoms, stem cells are defined by their clonogenic properties and are maintained by intercellular signals. The signaling molecules are different in plants and animals stem cell niches, but the roles of argonaute and polycomb group proteins suggest that there are some molecular similarities.

  12. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  13. Reversing breast cancer stem cell into breast somatic stem cell.

    PubMed

    Wijaya, L; Agustina, D; Lizandi, A O; Kartawinata, M M; Sandra, F

    2011-02-01

    Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research.

  14. Low-Dose, Long-Wave UV Light Does Not Affect Gene Expression of Human Mesenchymal Stem Cells.

    PubMed

    Wong, Darice Y; Ranganath, Thanmayi; Kasko, Andrea M

    2015-01-01

    Light is a non-invasive tool that is widely used in a range of biomedical applications. Techniques such as photopolymerization, photodegradation, and photouncaging can be used to alter the chemical and physical properties of biomaterials in the presence of live cells. Long-wave UV light (315 nm-400 nm) is an easily accessible and commonly used energy source for triggering biomaterial changes. Although exposure to low doses of long-wave UV light is generally accepted as biocompatible, most studies employing this wavelength only establish cell viability, ignoring other possible (non-toxic) effects. Since light exposure of wavelengths longer than 315 nm may potentially induce changes in cell behavior, we examined changes in gene expression of human mesenchymal stem cells exposed to light under both 2D and 3D culture conditions, including two different hydrogel fabrication techniques, decoupling UV exposure and radical generation. While exposure to long-wave UV light did not induce significant changes in gene expression regardless of culture conditions, significant changes were observed due to scaffold fabrication chemistry and between cells plated in 2D versus encapsulated in 3D scaffolds. In order to facilitate others in searching for more specific changes between the many conditions, the full data set is available on Gene Expression Omnibus for querying.

  15. The Populus Class III HD ZIP transcription factor POPCORONA affects cell differentiation during secondary growth of woody stems.

    PubMed

    Du, Juan; Miura, Eriko; Robischon, Marcel; Martinez, Ciera; Groover, Andrew

    2011-02-28

    The developmental mechanisms regulating cell differentiation and patterning during the secondary growth of woody tissues are poorly understood. Class III HD ZIP transcription factors are evolutionarily ancient and play fundamental roles in various aspects of plant development. Here we investigate the role of a Class III HD ZIP transcription factor, POPCORONA, during secondary growth of woody stems. Transgenic Populus (poplar) trees expressing either a miRNA-resistant POPCORONA or a synthetic miRNA targeting POPCORONA were used to infer function of POPCORONA during secondary growth. Whole plant, histological, and gene expression changes were compared for transgenic and wild-type control plants. Synthetic miRNA knock down of POPCORONA results in abnormal lignification in cells of the pith, while overexpression of a miRNA-resistant POPCORONA results in delayed lignification of xylem and phloem fibers during secondary growth. POPCORONA misexpression also results in coordinated changes in expression of genes within a previously described transcriptional network regulating cell differentiation and cell wall biosynthesis, and hormone-related genes associated with fiber differentiation. POPCORONA illustrates another function of Class III HD ZIPs: regulating cell differentiation during secondary growth.

  16. Low-Dose, Long-Wave UV Light Does Not Affect Gene Expression of Human Mesenchymal Stem Cells

    PubMed Central

    Wong, Darice Y.; Ranganath, Thanmayi; Kasko, Andrea M.

    2015-01-01

    Light is a non-invasive tool that is widely used in a range of biomedical applications. Techniques such as photopolymerization, photodegradation, and photouncaging can be used to alter the chemical and physical properties of biomaterials in the presence of live cells. Long-wave UV light (315 nm–400 nm) is an easily accessible and commonly used energy source for triggering biomaterial changes. Although exposure to low doses of long-wave UV light is generally accepted as biocompatible, most studies employing this wavelength only establish cell viability, ignoring other possible (non-toxic) effects. Since light exposure of wavelengths longer than 315 nm may potentially induce changes in cell behavior, we examined changes in gene expression of human mesenchymal stem cells exposed to light under both 2D and 3D culture conditions, including two different hydrogel fabrication techniques, decoupling UV exposure and radical generation. While exposure to long-wave UV light did not induce significant changes in gene expression regardless of culture conditions, significant changes were observed due to scaffold fabrication chemistry and between cells plated in 2D versus encapsulated in 3D scaffolds. In order to facilitate others in searching for more specific changes between the many conditions, the full data set is available on Gene Expression Omnibus for querying. PMID:26418040

  17. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2009-01-23

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

  18. Multipotent Stem Cell and Reproduction.

    PubMed

    Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sobhani, Aligholi

    2016-01-01

    Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. The accessibility and adaptability of these amazing cells create them a great therapeutic choice for different part of medical approaches, and it becomes interesting topic in the scientific researches to found obvious method for the most advantageous use of MSC-based therapies. Recent studies in the field of stem cell biology have provided new perspectives and opportunities for the treatment of infertility disorders.

  19. Stem cell mobilization.

    PubMed

    Cottler-Fox, Michele H; Lapidot, Tsvee; Petit, Isabelle; Kollet, Orit; DiPersio, John F; Link, Dan; Devine, Steven

    2003-01-01

    Successful blood and marrow transplant (BMT), both autologous and allogeneic, requires the infusion of a sufficient number of hematopoietic progenitor/stem cells (HPCs) capable of homing to the marrow cavity and regenerating a full array of hematopoietic cell lineages in a timely fashion. At present, the most commonly used surrogate marker for HPCs is the cell surface marker CD34, identified in the clinical laboratory by flow cytometry. Clinical studies have shown that infusion of at least 2 x 10(6) CD34(+) cells/kg recipient body weight results in reliable engraftment as measured by recovery of adequate neutrophil and platelet counts approximately 14 days after transplant. Recruitment of HPCs from the marrow into the blood is termed mobilization, or, more commonly, stem cell mobilization. In Section I, Dr. Tsvee Lapidot and colleagues review the wide range of factors influencing stem cell mobilization. Our current understanding focuses on chemokines, proteolytic enzymes, adhesion molecules, cytokines and stromal cell-stem cell interactions. On the basis of this understanding, new approaches to mobilization have been designed and are now starting to undergo clinical testing. In Section II, Dr. Michele Cottler-Fox describes factors predicting the ability to mobilize the older patient with myeloma. In addition, clinical approaches to improving collection by individualizing the timing of apheresis and adjusting the volume of blood processed to achieve a desired product are discussed. Key to this process is the daily enumeration of blood CD34(+) cells. Newer methods of enumerating and mobilizing autologous blood HPCs are discussed. In Section III, Dr. John DiPersio and colleagues provide data on clinical results of mobilizing allogeneic donors with G-CSF, GM-CSF and the combination of both as relates to the number and type of cells collected by apheresis. Newer methods of stem cell mobilization as well as the relationship of graft composition on immune reconstitution

  20. Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

    PubMed Central

    Bravenboer, Nathalie

    2016-01-01

    During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs). hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL) for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold), as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair. PMID:27667999

  1. Cloning of Mammary Stem Cells

    DTIC Science & Technology

    2001-11-01

    these parity-induced cells do represent a totipotent mammary stem cell population per se, but these cells might support stem cell maintenance as... Stem Cells PRINCIPAL INVESTIGATOR: Dr. Kay-Uwe Wagner CONTRACTING ORGANIZATION: University of Nebraska Medical Center Omaha, Nebraska 68198-6810 REPORT...Mammary Stem Cells DAMD17-00-1-0641 6. AUTHOR(S) Dr. Kay-Uwe Wagner 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT

  2. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

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

  3. Does minor histocompatibility antigen HA‐1 disparity affect the occurrence of graft‐versus‐host disease in tunisian recipients of hematopoietic stem cells?

    PubMed Central

    Sellami, Mohamed Hichem; Torjemane, Lamia; de Arias, Alejandro Espadas; Kaabi, Houda; Ladeb, Saloua; Poli, Francesca; Othmane, Tarek Ben; Hmida, Slama

    2010-01-01

    INTRODUCTION: Minor histocompatibility antigen HA‐1 (MiHAg‐HA‐1) disparity between a patient and his or her human leukocyte antigen (HLA) genoidentical donor has been widely associated with an increased risk of graft‐versus‐host disease following allogeneic hematopoietic stem cell transplantation. OBJECTIVE: To examine the effect of HA‐1 disparity on the incidence of both acute and chronic graft‐versus‐host disease in Tunisian recipients of hematopoietic stem cells. METHODS: A total of 60 patients and their 60 respective sibling hematopoietic stem cell donors were enrolled in this study. All patients prophylactically received cyclosporine A and/or methotrexate for graft‐versus‐host disease. An HA‐1 genotyping assay was performed with the SSP‐PCR method, and HLA‐A*0201‐ and/or HLA‐A*0206‐positive samples were identified using the Luminex HLA typing method. RESULTS: The Luminex HLA typing assay showed that 54 patients were positive for either the HLA‐A*0201 or HLA‐A*0206 alleles. Among these cases, six pairs were mismatched for MiHAg‐HA‐1. Both acute and chronic graft‐versus‐host disease occurred in four mismatched patients (Fisher's p‐values were 0.044 and 0.170, respectively). A univariate logistic regression model analysis showed that only acute graft‐versus‐host disease may be affected by recipient MiHAg‐HA‐1 disparity (p: 0.041, OR: 6.727), while chronic graft‐versus‐host disease correlates with both age and recipient/donor sex mismatch (p: 0.014, OR: 8.556 and p: 0.033, OR: 8.664, respectively). CONCLUSION: Our findings support previously reported data suggesting a significant association between HA‐1 disparity and the risk of acute graft‐versus‐host disease following hematopoietic stem cell transplantation. PMID:21243279

  4. Fifth Annual Stem Cell Summit.

    PubMed

    Knowlton, Daniel

    2010-04-01

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

  5. Bone Regeneration Mediated by BMP4-Expressing Muscle-Derived Stem Cells Is Affected by Delivery System

    PubMed Central

    Usas, Arvydas; Ho, Andrew M.; Cooper, Gregory M.; Olshanski, Anne; Peng, Hairong

    2009-01-01

    This study investigated the delivery of bone morphogenetic protein (BMP)4-secreting muscle-derived stem cells (MDSC-B4) capable of inducing bone formation in mice using collagen gel (CG), fibrin sealant (FS), and gelatin sponge carriers. After implanting these various cell-loaded scaffolds intramuscularly or into critical-size skull defects, we measured the extent of heterotopic ossification and calvarial defect healing over a 6-week period via radiographic, radiomorphometric, histological, and micro-computed tomography analyses. As expected, in the absence of MDSC-B4, there was no ectopic ossification and only minimal calvarial regeneration using each type of scaffold. Although CG and gelatin sponges loaded with BMP4-secreting cells produced the most ectopic bone, FS constructs produced bone with comparably less mineralization. In the mouse calvaria, we observed MDSC-B4-loaded scaffolds able to promote bone defect healing to a variable degree, but there were differences between these implants in the volume, shape, and morphology of regenerated bone. MDSC-B4 delivery in a gelatin sponge produced hypertrophic bone, whereas delivery in a CG and FS healed the defect with bone that closely resembled the quantity and configuration of native calvarium. In summary, hydrogels are suitable carriers for osteocompetent MDSCs in promoting bone regeneration, especially at craniofacial injury sites. PMID:19061430

  6. Iatrogenic limbal stem cell deficiency.

    PubMed Central

    Holland, E J; Schwartz, G S

    1997-01-01

    PURPOSE: To describe a group of patients with limbal stem cell (SC) deficiency without prior diagnosis of a specific disease entity known to be causative of SC deficiency. METHODS: We performed a retrospective review of the records of all patients with ocular surface disease presenting to the University of Minnesota between 1987 and 1996. Patients were categorized according to etiology of limbal deficiency. Patients who did not have a specific diagnosis previously described as being causative for limbal deficiency were analyzed. Risk factors, clinical findings and sequelae were evaluated. RESULTS: Eight eyes of six patients with stem cell deficiency not secondary to a known diagnosis were described. All eyes had prior ocular surgery involving the corneoscleral limbus. Six eyes had been on chronic topical medications and all eyes had concurrent external disease such as pterygium, keratoconjunctivitis sicca, rosacea or herpes simplex virus keratitis. All eyes had superior quadrants affected corresponding to areas of prior limbal surgery. Sequelae of disease included corneal scarring and neo-vascularization, and five eyes had with visual acuity of 20/200 or worse. CONCLUSIONS: Because the epitheliopathy started peripherally and extended centrally in all patients, we feel it represents a stem cell deficiency. The fact that all patients were affected superiorly, at sites of a prior limbal surgical incision, points to surgical trauma to the SC as the likely major etiologic factor for the deficiency. The surgical trauma to the limbal SC probably made these cells more susceptible to damage from other external disease influences and toxicity from chronic topical medications. Because the stem cell deficiency is secondary to prior ocular surgery and chronic topical medications, we propose the term "iatrogenic limbal stem cell deficiency". Images FIGURE 1 FIGURE 2A FIGURE 2B FIGURE 3A FIGURE 3B PMID:9440165

  7. Stem Cell Transplants (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Stem Cell Transplants KidsHealth > For Parents > Stem Cell Transplants A A A What's in this article? ... Recovery Coping en español Trasplantes de células madre Stem cells are cells in the body that have the ...

  8. Stem cells and transplant arteriosclerosis.

    PubMed

    Xu, Qingbo

    2008-05-09

    Stem cells can differentiate into a variety of cells to replace dead cells or to repair damaged tissues. Recent evidence indicates that stem cells are involved in the pathogenesis of transplant arteriosclerosis, an alloimmune initiated vascular stenosis that often results in transplant organ failure. Although the pathogenesis of transplant arteriosclerosis is not yet fully understood, recent developments in stem cell research have suggested novel mechanisms of vascular remodeling in allografts. For example, stem cells derived from the recipient may repair damaged endothelial cells of arteries in transplant organs. Further evidence suggests that stem cells or endothelial progenitor cells may be released from both bone marrow and non-bone marrow tissues. Vascular stem cells appear to replenish cells that died in donor vessels. Concomitantly, stem/progenitor cells may also accumulate in the intima, where they differentiate into smooth muscle cells. However, several issues concerning the contribution of stem cells to the pathogenesis of transplant arteriosclerosis are controversial, eg, whether bone marrow-derived stem cells can differentiate into smooth muscle cells that form neointimal lesions of the vessel wall. This review summarizes recent research on the role of stem cells in transplant arteriosclerosis, discusses the mechanisms of stem cell homing and differentiation into mature endothelial and smooth muscle cells, and highlights the controversial issues in the field.

  9. Laser biomodulation on stem cells

    NASA Astrophysics Data System (ADS)

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

    2001-08-01

    Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

  10. Feline foamy virus adversely affects feline mesenchymal stem cell culture and expansion: implications for animal model development.

    PubMed

    Arzi, Boaz; Kol, Amir; Murphy, Brian; Walker, Naomi J; Wood, Joshua A; Clark, Kaitlin; Verstraete, Frank J M; Borjesson, Dori L

    2015-04-01

    Mesenchymal stem cells (MSCs) are a promising therapeutic option for various immune-mediated and inflammatory disorders due to their potent immunomodulatory and trophic properties. Naturally occurring diseases in large animal species may serve as surrogate animal models of human disease, as they may better reflect the complex genetic, environmental, and physiologic variation present in outbred populations. We work with naturally occurring diseases in large animal species to better understand how MSCs work and to facilitate optimal translation of MSC-based therapies. We are investigating the use of MSC therapy for a chronic oral inflammatory disease in cats. During our efforts to expand fat-derived feline MSCs (fMSCs), we observed that∼50% of the cell lines developed giant foamy multinucleated cells in later passages. These morphologic alterations were associated with proliferation arrest. We hypothesized that the cytopathic effects were caused by infection with a retrovirus, feline foamy virus (FFV). Using transmission electron microscopy, polymerase chain reaction, and in vitro assays, we determined that syncytial cell formation and proliferation arrest in fMSCs were caused by FFV strains that were highly homologous to previously reported FFV strains. We determined that the antiretroviral drug, tenofovir, may be used to support ex vivo expansion and salvage of FFV-infected fMSC lines. MSC lines derived from specific pathogen-free cats do not appear to be infected with FFV and may be a source of allogeneic fMSCs for clinical application. FFV infection of fMSC lines may hinder large-scale expansion of autologous MSC for therapeutic use in feline patients.

  11. Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

    PubMed Central

    Kol, Amir; Murphy, Brian; Walker, Naomi J.; Wood, Joshua A.; Clark, Kaitlin; Verstraete, Frank J.M.; Borjesson, Dori L.

    2015-01-01

    Abstract Mesenchymal stem cells (MSCs) are a promising therapeutic option for various immune-mediated and inflammatory disorders due to their potent immunomodulatory and trophic properties. Naturally occurring diseases in large animal species may serve as surrogate animal models of human disease, as they may better reflect the complex genetic, environmental, and physiologic variation present in outbred populations. We work with naturally occurring diseases in large animal species to better understand how MSCs work and to facilitate optimal translation of MSC-based therapies. We are investigating the use of MSC therapy for a chronic oral inflammatory disease in cats. During our efforts to expand fat-derived feline MSCs (fMSCs), we observed that∼50% of the cell lines developed giant foamy multinucleated cells in later passages. These morphologic alterations were associated with proliferation arrest. We hypothesized that the cytopathic effects were caused by infection with a retrovirus, feline foamy virus (FFV). Using transmission electron microscopy, polymerase chain reaction, and in vitro assays, we determined that syncytial cell formation and proliferation arrest in fMSCs were caused by FFV strains that were highly homologous to previously reported FFV strains. We determined that the antiretroviral drug, tenofovir, may be used to support ex vivo expansion and salvage of FFV-infected fMSC lines. MSC lines derived from specific pathogen-free cats do not appear to be infected with FFV and may be a source of allogeneic fMSCs for clinical application. FFV infection of fMSC lines may hinder large-scale expansion of autologous MSC for therapeutic use in feline patients. PMID:25404388

  12. [Stem cell colloquy: conclusion].

    PubMed

    Tubiana, Maurice

    2002-10-01

    The stem cell data presented and discussed during the symposium raise the hope that important medical progress can be made in several fields: neuro-degenerative diseases, those linked to cellular deficit, some aspects of aging linked to cellular degeneration, and the treatment of cancers that may harm normal tissues at risk of being infiltrated by malignant cells. Three main types of stem cells are available. (i) Those present in normal adult tissue: contrary to what was believed, some data suggest that certain adult stem cells have a great plasticity (they can differentiate into cells different from those in tissues from which they were taken) and can proliferate in vitro without losing their properties. Nevertheless, their use faces several obstacles: in ill or elderly subjects, then these cells can be limited in number or not multiply well in vitro. In this case, auto-grafting of the cells cannot be used. They must be sought in another subject, and allo-grafting causes difficult and sometimes insoluble problems of immunological tolerance. (ii) Embryonic stem cells from surplus human embryos, obtained by in vitro fertilisation, which the parents decide not to use: these cells have a great potential for proliferation and differentiation, but can also encounter problems of immunological intolerance. (iii) Cells obtained from cell nuclear transfer in oocytes: these cells are well tolerated, since they are genetically and immunologically identical to those of the host. All types of stem cells can be obtained with them. However, they do present problems. For obtaining them, female oocytes are needed, which could lead to their commercialization. Moreover, the first steps for obtaining these cells are identical to those used in reproductive cloning. It therefore appears that each type of cell raises difficult scientific and practical problems. More research is needed to overcome these obstacles and to determine which type of stem cell constitutes the best solution for

  13. Neural stem cells: an overview.

    PubMed

    Parati, E A; Pozzi, S; Ottolina, A; Onofrj, M; Bez, A; Pagano, S F

    2004-01-01

    Multipotent stem cells are present in the majority of mammalian tissues where they are a renewable source of specialized cells. According to the several biological portions from which multipotent stem cells can be derived, they are characterized as a) embryonic stem cells (ESCs) isolated from the pluripotent inner-cell mass of the pre-implantation blastocyste-stage embryo; b) multipotent fetal stem cells (FSCs) from aborted fetuses; and c) adult stem cells (ASCs) localized in small zones of several organs known as "niche" where a subset of tissue cells and extracellular substrates can indefinitely house one or more stem cells and control their self-renewal and progeny production in vivo. ECSs have an high self-renewing capacity, plasticity and pluripotency over the years. Pluripotency is a property that makes a stem cell able to give rise to all cell type found in the embryo and adult animals.

  14. Stem cells and healthy aging.

    PubMed

    Goodell, Margaret A; Rando, Thomas A

    2015-12-04

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.

  15. Stem Cells and Female Reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    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

  16. Inflammation and cancer stem cells.

    PubMed

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

    2014-04-10

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

  17. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  18. Senescence-Associated Molecular and Epigenetic Alterations in Mesenchymal Stem Cell Cultures from Amniotic Fluid of Normal and Fetus-Affected Pregnancy

    PubMed Central

    Savickienė, Jūratė; Baronaitė, Sandra; Zentelytė, Aistė; Treigytė, Gražina

    2016-01-01

    Human amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) are interesting for their multilineage differentiation potential and wide range of therapeutic applications due to the ease of culture expansion. However, MSCs undergo replicative senescence. So far, the molecular mechanisms that underlie fetal diseases and cell senescence are still poorly understood. Here, we analyzed senescence-associated morphologic, molecular, and epigenetic characteristics during propagation of MSCs derived from AF of normal and fetus-affected pregnancy. AF-MSCs cultures from both cell sources displayed quite similar morphology and expression of specific cell surface (CD44, CD90, and CD105) and stemness (Oct4, Nanog, Sox2, and Rex1) markers but had interindividual variability in proliferation capability and time to reach senescence. Within passages 4 and 8, senescent cultures exhibited typical morphological features, senescence-associated β-galactosidase activity, increased levels of p16, and decreased levels of miR-17 and miR-21 but showed differential expression of p21, p53, and ATM dependently on the onset of cell senescence. These differences correlated with changes in the level of chromatin modifiers (DNMT1 and HDAC1) and polycomb group proteins (EZH2, SUZ12, and BMI1) paralleling with changes in the expression of repressive histone marks (H3K9me3 and H3K27me3) and stemness markers (Oct4, Nanog, Sox2, and Rex1). Therefore epigenetic factors are important for AF-MSCs senescence process that may be related with individuality of donor or a fetus malignancy status. PMID:27803714

  19. Materials as stem cell regulators

    PubMed Central

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

    2014-01-01

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

  20. Materials as stem cell regulators

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  1. Information on Stem Cell Research

    MedlinePlus

    ... Home » Current Research » Focus on Research Focus on Stem Cell Research Stem cells possess the unique ability to differentiate into many ... they also retain the ability to produce more stem cells, a process termed self-renewal. There are multiple ...

  2. High prevalence of potential drug interactions affecting mycophenolic acid pharmacokinetics in nonmyeloablative hematopoietic stem cell transplant recipients

    PubMed Central

    Jaklič, Alenka; Collins, Carol J.; Mrhar, Aleš; Sorror, Mohamed L.; Sandmaier, Brenda M.; Bemer, Meagan J.; Locatelli, Igor; McCune, Jeannine S.

    2013-01-01

    Objective: Mycophenolic acid (MPA) exposure is associated with clinical outcomes in hematopoietic cell transplant (HCT) recipients. Various drug interaction studies, predominantly in healthy volunteers or solid organ transplant recipients, have identified medications which impact MPA pharmacokinetics. Recipients of nonmyeloablative HCT, however, have an increased burden of comorbidities, potentially increasing the number of concomitant medications and potential drug interactions (PDI) affecting MPA exposure. Thus, we sought to be the first to characterize these PDI in nonmyeloablative HCT recipients. Materials and methods: We compiled PDI affecting MPA pharmacokinetics and characterized the prevalence of PDI in nonmyeloablative HCT recipients. A comprehensive literature evaluation of four databases and PubMed was conducted to identify medications with PDI affecting MPA pharmacokinetics. Subsequently, a retrospective medication review was conducted to characterize the cumulative PDI burden, defined as the number of PDI for an individual patient over the first 21 days after allogeneic graft infusion, in 84 nonmyeloablative HCT recipients. Results: Of the 187 concomitant medications, 11 (5.9%) had a PDI affecting MPA pharmacokinetics. 87% of 84 patients had one PDI, with a median cumulative PDI burden of 2 (range 0 – 4). The most common PDI, in descending order, were cyclosporine, omeprazole and pantoprazole. Conclusion: Only a minority of medications (5.9%) have a PDI affecting MPA pharmacokinetics. However, the majority of nonmyeloablative HCT recipients had a PDI, with cyclosporine and the proton pump inhibitors being the most common. A better understanding of PDI and their management should lead to safer medication regimens for nonmyeloablative HCT recipients. PMID:23782584

  3. Familial Dysautonomia (FD) Human Embryonic Stem Cell Derived PNS Neurons Reveal that Synaptic Vesicular and Neuronal Transport Genes Are Directly or Indirectly Affected by IKBKAP Downregulation

    PubMed Central

    Kantor, Gal; Cheishvili, David; Even, Aviel; Birger, Anastasya; Turetsky, Tikva; Gil, Yaniv; Even-Ram, Sharona; Aizenman, Einat; Bashir, Nibal; Maayan, Channa; Razin, Aharon; Reubinoff, Benjamim E.; Weil, Miguel

    2015-01-01

    A splicing mutation in the IKBKAP gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we found new molecular insights for the IKAP role and the impact of the FD mutation in the human PNS lineage by using a novel and unique human embryonic stem cell (hESC) line homozygous to the FD mutation originated by pre implantation genetic diagnosis (PGD) analysis. We found that IKBKAP downregulation during PNS differentiation affects normal migration in FD-hESC derived neural crest cells (NCC) while at later stages the PNS neurons show reduced intracellular colocalization between vesicular proteins and IKAP. Comparative wide transcriptome analysis of FD and WT hESC-derived neurons together with the analysis of human brains from FD and WT 12 weeks old embryos and experimental validation of the results confirmed that synaptic vesicular and neuronal transport genes are directly or indirectly affected by IKBKAP downregulation in FD neurons. Moreover we show that kinetin (a drug that corrects IKBKAP alternative splicing) promotes the recovery of IKAP expression and these IKAP functional associated genes identified in the study. Altogether, these results support the view that IKAP might be a vesicular like protein that might be involved in neuronal transport in hESC derived PNS neurons. This function seems to be mostly affected in FD-hESC derived PNS neurons probably reflecting some PNS neuronal dysfunction observed in FD. PMID:26437462

  4. Familial Dysautonomia (FD) Human Embryonic Stem Cell Derived PNS Neurons Reveal that Synaptic Vesicular and Neuronal Transport Genes Are Directly or Indirectly Affected by IKBKAP Downregulation.

    PubMed

    Lefler, Sharon; Cohen, Malkiel A; Kantor, Gal; Cheishvili, David; Even, Aviel; Birger, Anastasya; Turetsky, Tikva; Gil, Yaniv; Even-Ram, Sharona; Aizenman, Einat; Bashir, Nibal; Maayan, Channa; Razin, Aharon; Reubinoff, Benjamim E; Weil, Miguel

    2015-01-01

    A splicing mutation in the IKBKAP gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we found new molecular insights for the IKAP role and the impact of the FD mutation in the human PNS lineage by using a novel and unique human embryonic stem cell (hESC) line homozygous to the FD mutation originated by pre implantation genetic diagnosis (PGD) analysis. We found that IKBKAP downregulation during PNS differentiation affects normal migration in FD-hESC derived neural crest cells (NCC) while at later stages the PNS neurons show reduced intracellular colocalization between vesicular proteins and IKAP. Comparative wide transcriptome analysis of FD and WT hESC-derived neurons together with the analysis of human brains from FD and WT 12 weeks old embryos and experimental validation of the results confirmed that synaptic vesicular and neuronal transport genes are directly or indirectly affected by IKBKAP downregulation in FD neurons. Moreover we show that kinetin (a drug that corrects IKBKAP alternative splicing) promotes the recovery of IKAP expression and these IKAP functional associated genes identified in the study. Altogether, these results support the view that IKAP might be a vesicular like protein that might be involved in neuronal transport in hESC derived PNS neurons. This function seems to be mostly affected in FD-hESC derived PNS neurons probably reflecting some PNS neuronal dysfunction observed in FD.

  5. Inefficiency in macromolecular transport of SCS-based microcapsules affects viability of primary human mesenchymal stem cells but not of immortalized cells.

    PubMed

    Sanz-Nogués, Clara; Horan, Jason; Thompson, Kerry; Howard, Linda; Ryan, Gerard; Kassem, Moustapha; O'Brien, Timothy

    2015-11-01

    Microcapsules made of sodium cellulose sulphate (SCS) and poly-diallyl-dimethyl-ammonium chloride (pDADMAC) have been employed to encapsulate a wide range of established cell lines for several applications. However, little is known about the encapsulation of primary cells including human mesenchymal stem cells (hMSCs). Human MSCs are of interest in regenerative medicine applications due to pro-angiogenic, anti-inflammatory and immunomodulatory properties, which result from paracrine effects of this cell type. In the present work we have encapsulated primary hMSCs and hMSC-TERT immortalized cells and compared their behavior and in vitro angiogenic potential. We found that, although both cell types were able to secret angiogenic factors such as VEGF, there was a marked reduction of primary hMSC viability compared to hMSC-TERT cells when cultured in these microcapsules. Moreover, this applied to other primary cell cultures such as primary human fibroblasts but not to other cell lines such as human embryonic kidney 293 (HEK293) cells. We found that the microcapsule membrane had a molecular weight cut-off below a critical size, which caused impairment in the diffusion of essential nutrients and had a more detrimental effect on the viability of primary cell cultures compared to cell lines and immortalized cells.

  6. Transplantation of human umbilical cord-derived mesenchymal stems cells for the treatment of Becker muscular dystrophy in affected pedigree members.

    PubMed

    Li, Pang; Cui, Kai; Zhang, Bo; Wang, Zhendan; Shen, Yangyang; Wang, Xiangyu; Zhang, Jianbo; Tong, Feng; Li, Sheng

    2015-04-01

    The regeneration of muscle tissue has been achieved using multipotent mesenchymal stem cells in mouse models of injured skeletal muscle. In the present study, the utility of multipotent human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in the treatment of Becker muscular dystrophy (BMD), a genetic disease where muscle tissue fails to regenerate, was examined in members from a pedigree affected by BMD. The disease status was evaluated in 4 affected pedigree members (II1, II2, II3 and III2; aged 50, 46, 42 and 6 years, respectively). The transplantation of the hUC‑MSCs (performed on 3 patients, I2, II3 and III2) was performed by infusion with an intravenous drip over a 30‑min period, and the patients were evaluated at 1, 3, 4 and 12 weeks following the procedure. The evaluation was based on physical characteristics, as well as on molecular testing for serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels and a histological examination of muscle biopsies. The patients suffered no adverse reactions in response to the transplantation of the hUC‑MSCs. At 1 week following transplantation all 3 patients showed improvement in the muscle force of the limbs, muscle size and daily activity. The walking gait of patient III2 had improved by 1 week post-transplantation and reached a normal status by 12 weeks. Serum CK and LDH levels were decreased relative to the baseline levels. A histological examination of muscle biopsies displayed no obvious tissue regeneration. In conclusion, the treatment of patients with BMD using hUC-MSCs was safe and of therapeutic benefit that lasted for up to 12 weeks. hUC-MSCs are, therefore, a potential cell therapy-based treatment option for patients with muscular dystrophies.

  7. Peripheral blood stem cell mobilization failure.

    PubMed

    Kurnaz, Fatih; Kaynar, Leylagül

    2015-08-01

    Autologous hematopoietic stem cell transplantation (HSCT) is an important and often life saving treatment for many hematological malignancies and selected solid tumors. To rescue hematopoiesis after high-dose chemotherapy in autologous HSCT depends on maintaining sufficient stem cells. Hematopoietic stem cells and progenitor cells expressing CD34 in the BM are mobilized into the circulation with granulocyte-colony stimulating factor ± chemotherapy prior to autologous HSCT. One of the most important factors for success of autologous HSCT is hematopoietic stem cell (HSC) count. Minimum threshold for the engraftment of hematopoietic cells is accepted as 2 × 10(6) CD34 + cells/kg especially for platelet engraftment. Below this level it is defined as stem cell mobilization failure. There are several factors affecting stem cell mobilization: prior chemotherapy (such as fludarabine, melphalan, lenalidomide) and radiotherapy, age, type of disease, bone marrow cellularity. We tried to summarize the reasons of peripheral stem cell mobilization failure.

  8. Stem cells in dentistry--part I: stem cell sources.

    PubMed

    Egusa, Hiroshi; Sonoyama, Wataru; Nishimura, Masahiro; Atsuta, Ikiru; Akiyama, Kentaro

    2012-07-01

    Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties.

  9. Breast Cancer Stem Cells

    PubMed Central

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

    2012-01-01

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

  10. Stem cells for the treatment of diabetes.

    PubMed

    Noguchi, Hirofumi

    2007-02-01

    Diabetes mellitus is a devastating disease and over 6% of the population is affected worldwide. The success achieved over the last few years with islet transplantation suggest that diabetes can be cured by the replenishment of deficient beta cells. These observations are proof of concept and have intensified interest in treating diabetes or other diseases not only by cell transplantation but also by stem cells. Work with ES cells has not yet produced cells with the phenotype of true beta cells, but there has been recent progress in directing ES cells to the endoderm. Bone marrow-derived stem cells could initiate pancreatic regeneration. Pancreatic stem/progenitor cells have been identified, and the formation of new beta cells from duct, acinar and liver cells is an active area of investigation. Some agents including glucagon-like peptide-1/exendin-4 can stimulate the regeneration of beta cells in vivo. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. New technology, known as protein transduction technology, facilitates the differentiation of stem cells into insulin-producing cells. Recent progress in the search for new sources of beta cells has opened up several possibilities for the development of new treatments for diabetes.

  11. Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood

    PubMed Central

    Llobet, Laura; Toivonen, Janne M.; Montoya, Julio; Ruiz-Pesini, Eduardo; López-Gallardo, Ester

    2015-01-01

    ABSTRACT Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system. The tested concentrations have been previously reported in human blood. Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis. PMID:26398948

  12. Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood.

    PubMed

    Llobet, Laura; Toivonen, Janne M; Montoya, Julio; Ruiz-Pesini, Eduardo; López-Gallardo, Ester

    2015-11-01

    Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system. The tested concentrations have been previously reported in human blood. Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis.

  13. (Re)defining stem cells.

    PubMed

    Shostak, Stanley

    2006-03-01

    Stem-cell nomenclature is in a muddle! So-called stem cells may be self-renewing or emergent, oligopotent (uni- and multipotent) or pluri- and totipotent, cells with perpetual embryonic features or cells that have changed irreversibly. Ambiguity probably seeped into stem cells from common usage, flukes in biology's history beginning with Weismann's divide between germ and soma and Haeckel's biogenic law and ending with contemporary issues over the therapeutic efficacy of adult versus embryonic cells. Confusion centers on tissue dynamics, whether stem cells are properly members of emerging or steady-state populations. Clarity might yet be achieved by codifying differences between cells in emergent populations, including embryonic stem and embryonic germ (ES and EG) cells in tissue culture as opposed to self-renewing (SR) cells in steady-state populations.

  14. Pancreatic cancer stem cells.

    PubMed

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

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

  15. Activation of the Tor/Myc signaling axis in intestinal stem and progenitor cells affects longevity, stress resistance and metabolism in drosophila.

    PubMed

    Strilbytska, Olha M; Semaniuk, Uliana V; Storey, Kenneth B; Edgar, Bruce A; Lushchak, Oleh V

    2017-01-01

    The TOR (target of rapamycin) signaling pathway and the transcriptional factor Myc play important roles in growth control. Myc acts, in part, as a downstream target of TOR to regulate the activity and functioning of stem cells. Here we explore the role of TOR-Myc axis in stem and progenitor cells in the regulation of lifespan, stress resistance and metabolism in Drosophila. We found that both overexpression of rheb and myc-rheb in midgut stem and progenitor cells decreased the lifespan and starvation resistance of flies. TOR activation caused higher survival under malnutrition conditions. Furthermore, we demonstrate gut-specific activation of JAK/STAT and insulin signaling pathways to control gut integrity. Both genetic manipulations had an impact on carbohydrate metabolism and transcriptional levels of metabolic genes. Our findings indicate that activation of the TOR-Myc axis in midgut stem and progenitor cells influences a variety of traits in Drosophila.

  16. Curbing stem cell tourism in South Africa.

    PubMed

    Meissner-Roloff, Madelein; Pepper, Michael S

    2013-12-01

    Stem cells have received much attention globally due in part to the immense therapeutic potential they harbor. Unfortunately, malpractice and exploitation (financial and emotional) of vulnerable patients have also drawn attention to this field as a result of the detrimental consequences experienced by some individuals that have undergone unproven stem cell therapies. South Africa has had limited exposure to stem cells and their applications and, while any exploitation is detrimental to the field of stem cells, South Africa is particularly vulnerable in this regard. The current absence of adequate legislation and the inability to enforce existing legislation, coupled to the sea of misinformation available on the Internet could lead to an increase in illegitimate stem cell practices in South Africa. Circumstances are already precarious because of a lack of understanding of concepts involved in stem cell applications. What is more, credible and easily accessible information is not available to the public. This in turn cultivates fears born out of existing superstitions, cultural beliefs, rituals and practices. Certain cultural or religious concerns could potentially hinder the effective application of stem cell therapies in South Africa and novel ways of addressing these concerns are necessary. Understanding how scientific progress and its implementation will affect each individual and, consequently, the community, will be of cardinal importance to the success of the fields of stem cell therapy and regenerative medicine in South Africa. A failure to understand the ethical, cultural or moral ramifications when new scientific concepts are introduced could hinder the efficacy and speed of bringing discoveries to the patient. Neglecting proper procedure for establishing the field would lead to long delays in gaining public support in South Africa. Understanding the dangers of stem cell tourism - where vulnerable patients are subjected to unproven stem cell therapies that

  17. Stem cell applications in military medicine

    PubMed Central

    2011-01-01

    There are many similarities between health issues affecting military and civilian patient populations, with the exception of the relatively small but vital segment of active soldiers who experience high-energy blast injuries during combat. A rising incidence of major injuries from explosive devices in recent campaigns has further complicated treatment and recovery, highlighting the need for tissue regenerative options and intensifying interest in the possible role of stem cells for military medicine. In this review we outline the array of tissue-specific injuries typically seen in modern combat - as well as address a few complications unique to soldiers - and discuss the state of current stem cell research in addressing each area. Embryonic, induced-pluripotent and adult stem cell sources are defined, along with advantages and disadvantages unique to each cell type. More detailed stem cell sources are described in the context of each tissue of interest, including neural, cardiopulmonary, musculoskeletal and sensory tissues, with brief discussion of their potential role in regenerative medicine moving forward. Additional commentary is given to military stem cell applications aside from regenerative medicine, such as blood pharming, immunomodulation and drug screening, with an overview of stem cell banking and the unique opportunity provided by the military and civilian overlap of stem cell research. PMID:22011454

  18. Stem cell applications in military medicine.

    PubMed

    Christopherson, Gregory T; Nesti, Leon J

    2011-10-19

    There are many similarities between health issues affecting military and civilian patient populations, with the exception of the relatively small but vital segment of active soldiers who experience high-energy blast injuries during combat. A rising incidence of major injuries from explosive devices in recent campaigns has further complicated treatment and recovery, highlighting the need for tissue regenerative options and intensifying interest in the possible role of stem cells for military medicine. In this review we outline the array of tissue-specific injuries typically seen in modern combat - as well as address a few complications unique to soldiers--and discuss the state of current stem cell research in addressing each area. Embryonic, induced-pluripotent and adult stem cell sources are defined, along with advantages and disadvantages unique to each cell type. More detailed stem cell sources are described in the context of each tissue of interest, including neural, cardiopulmonary, musculoskeletal and sensory tissues, with brief discussion of their potential role in regenerative medicine moving forward. Additional commentary is given to military stem cell applications aside from regenerative medicine, such as blood pharming, immunomodulation and drug screening, with an overview of stem cell banking and the unique opportunity provided by the military and civilian overlap of stem cell research.

  19. The interference of Notch1 target Hes1 affects cell growth, differentiation and invasiveness of glioblastoma stem cells through modulation of multiple oncogenic targets.

    PubMed

    Cenciarelli, Carlo; Marei, Hany E; Zonfrillo, Manuela; Casalbore, Patrizia; Felsani, Armando; Giannetti, Stefano; Trevisi, Gianluca; Althani, Asma; Mangiola, Annunziato

    2017-02-02

    The invasive and lethal nature of Glioblastoma multiforme (GBM) necessitates the continuous identification of molecular targets and search of efficacious therapies to inhibit GBM growth. The GBM resistance to chemotherapy and radiation it is attributed to the existence of a rare fraction of cancer stem cells (CSC) that we have identified within the tumor core and in peritumor tissue of GBM. Since Notch1 pathway is a potential therapeutic target in brain cancer, earlier we highlighted that pharmacological inhibition of Notch1 signalling by γ-secretase inhibitor-X (GSI-X), reduced cell growth of some c-CSC than to their respective p-CSC, but produced negligible effects on cell cycle distribution, apoptosis and cell invasion. In the current study, we assessed the effects of Hes1-targeted shRNA, a Notch1 gene target, specifically on GBM CSC refractory to GSI-X. Depletion of Hes1 protein induces major changes in cell morphology, cell growth rate and in the invasive ability of shHes1-CSC in response to growth factor EGF. shHes1-CSC show a decrease of the stemness marker Nestin concurrently to a marked increase of neuronal marker MAP2 compared to pLKO.1-CSC. Those effects correlated with repression of EGFR protein and modulation of Stat3 phosphorylation at Y705 and S727 residues. In the last decade Stat3 has gained attention as therapeutic target in cancer but there is not yet any approved Stat3-based glioma therapy. Herein, we report that exposure to a Stat3/5 inhibitor, induced apoptosis either in shHes1-CSC or control cells. Taken together, Hes1 seems to be a favorable target but not sufficient itself to target GBM efficaciously, therefore a possible pharmacological intervention should provide for the use of anti-Stat3/5 drugs either alone or in combination regimen.

  20. Nuclear receptor regulation of stemness and stem cell differentiation

    PubMed Central

    Jeong, Yangsik

    2009-01-01

    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

  1. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    PubMed

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  2. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    PubMed Central

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  3. Structure and barrier properties of human embryonic stem cell-derived retinal pigment epithelial cells are affected by extracellular matrix protein coating.

    PubMed

    Sorkio, Anni; Hongisto, Heidi; Kaarniranta, Kai; Uusitalo, Hannu; Juuti-Uusitalo, Kati; Skottman, Heli

    2014-02-01

    Extracellular matrix (ECM) interactions play a vital role in cell morphology, migration, proliferation, and differentiation of cells. We investigated the role of ECM proteins on the structure and function of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells during their differentiation and maturation from hESCs into RPE cells in adherent differentiation cultures on several human ECM proteins found in native human Bruch's membrane, namely, collagen I, collagen IV, laminin, fibronectin, and vitronectin, as well as on commercial substrates of xeno-free CELLstart™ and Matrigel™. Cell pigmentation, expression of RPE-specific proteins, fine structure, as well as the production of basal lamina by hESC-RPE on different protein coatings were evaluated after 140 days of differentiation. The integrity of hESC-RPE epithelium and barrier properties on different coatings were investigated by measuring transepithelial resistance. All coatings supported the differentiation of hESC-RPE cells as demonstrated by early onset of cell pigmentation and further maturation to RPE monolayers after enrichment. Mature RPE phenotype was verified by RPE-specific gene and protein expression, correct epithelial polarization, and phagocytic activity. Significant differences were found in the degree of RPE cell pigmentation and tightness of epithelial barrier between different coatings. Further, the thickness of self-assembled basal lamina and secretion of the key ECM proteins found in the basement membrane of the native RPE varied between hESC-RPE cultured on compared protein coatings. In conclusion, this study shows that the cell culture substrate has a major effect on the structure and basal lamina production during the differentiation and maturation of hESC-RPE potentially influencing the success of cell integrations and survival after cell transplantation.

  4. Stem Cells, Redox Signaling, and Stem Cell Aging

    PubMed Central

    Liang, Raymond

    2014-01-01

    Abstract Significance: Functional stem cell decline has been postulated to result in loss of maintenance of tissue homeostasis leading to organismal decline and diseases of aging. Recent Advances: Recent findings implicate redox metabolism in the control of stem cell pool and stem cell aging. Although reactive oxygen species (ROS) are better known for their damaging properties to DNA, proteins and lipids, recent findings suggest that ROS may also be an integral physiological mediator of cellular signaling in primary cells. Critical Issues: Here we review recent published work on major signaling pathways and transcription factors that are regulated by ROS and mediate ROS regulation of stem cell fate. We will specifically focus on how alterations in this regulation may be implicated in disease and particularly in diseases of stem cell aging. In general, based on the work described here we propose a model in which ROS function as stem cell rheostat. Future Directions: Future work in elucidating how ROS control stem cell cycling, apoptotic machinery, and lineage determination should shed light on mechanisms whereby ROS may control stem cell aging. Antioxid. Redox Signal. 20, 1902–1916. PMID:24383555

  5. FACS Sorting Mammary Stem Cells.

    PubMed

    Iriondo, Oihana; Rábano, Miriam; Vivanco, María D M

    2015-01-01

    Fluorescent-activated cell sorting (FACS) represents one of the key techniques that have been used to isolate and characterize stem cells, including cells from the mammary gland. A combination of approaches, including recognition of cell surface antigens and different cellular activities, has facilitated the identification of stem cells from the healthy mammary gland and from breast tumors. In this chapter we describe the protocol to use FACS to separate breast cancer stem cells, but most of the general principles discussed could be applied to sort other types of cells.

  6. Targeting prostate cancer stem cells.

    PubMed

    Crea, Francesco; Mathews, Lesley A; Farrar, William L; Hurt, Elaine M

    2009-12-01

    Cancer stem cells are the sub-population of cells present within tumors responsible for tumorigenesis. These cells have unique biological properties including self-renewal and the ability to differentiate. Furthermore, it is thought that these cells are more resistant to conventional chemotherapy and, as a result, are responsible for patient relapse. We will discuss the identification of prostate cancer stem cells, their unique properties and how these cells may be targeted for more efficacious therapies.

  7. Stem cells for spine surgery

    PubMed Central

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

    2015-01-01

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

  8. Stem Cells behind the Barrier

    PubMed Central

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

    2013-01-01

    Epidermal stem cells sustain the adult skin for a lifetime through self-renewal and the production of committed progenitors. These stem cells generate progeny that will undergo terminal differentiation leading to the development of a protective epidermal barrier. Whereas the molecular mechanisms that govern epidermal barrier repair and renewal have been extensively studied, pathways controlling stem cell differentiation remain poorly understood. Asymmetric cell divisions, small non-coding RNAs (microRNAs), chromatin remodeling complexes, and multiple differentiation factors tightly control the balance of stem and progenitor cell proliferation and differentiation, and disruption of this balance leads to skin diseases. In this review, we summarize and discuss current advances in our understanding of the mechanisms regulating epidermal stem and progenitor cell differentiation, and explore new relationships for maintenance of skin barrier function. PMID:23812084

  9. [Stem cell therapy: an update].

    PubMed

    Coulombel, Laure

    2009-03-01

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

  10. Stem cells in pharmaceutical biotechnology.

    PubMed

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

    2011-11-01

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

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

    PubMed

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

    2010-12-01

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

  12. Extracellular matrix: A dynamic microenvironment for stem cell niche☆

    PubMed Central

    Gattazzo, Francesca; Urciuolo, Anna; Bonaldo, Paolo

    2014-01-01

    Background Extracellular matrix (ECM) is a dynamic and complex environment characterized by biophysical, mechanical and biochemical properties specific for each tissue and able to regulate cell behavior. Stem cells have a key role in the maintenance and regeneration of tissues and they are located in a specific microenvironment, defined as niche. Scope of review We overview the progresses that have been made in elucidating stem cell niches and discuss the mechanisms by which ECM affects stem cell behavior. We also summarize the current tools and experimental models for studying ECM–stem cell interactions. Major conclusions ECM represents an essential player in stem cell niche, since it can directly or indirectly modulate the maintenance, proliferation, self-renewal and differentiation of stem cells. Several ECM molecules play regulatory functions for different types of stem cells, and based on its molecular composition the ECM can be deposited and finely tuned for providing the most appropriate niche for stem cells in the various tissues. Engineered biomaterials able to mimic the in vivo characteristics of stem cell niche provide suitable in vitro tools for dissecting the different roles exerted by the ECM and its molecular components on stem cell behavior. General significance ECM is a key component of stem cell niches and is involved in various aspects of stem cell behavior, thus having a major impact on tissue homeostasis and regeneration under physiological and pathological conditions. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. PMID:24418517

  13. Concise review: limbal epithelial stem cell therapy: controversies and challenges.

    PubMed

    O'Callaghan, Anna R; Daniels, Julie T

    2011-12-01

    Limbal epithelial stem cells (LESCs) are a population of stem cells responsible for maintenance and repair of the corneal surface. Injury and disease can result in a deficiency of these stem cells, the vision affecting condition called limbal stem cell deficiency (LSCD) in which the cornea becomes opaque, vascularized, and inflamed. Cultured LESC therapy was first described in 1997;29:19231932-19231932.and LESCs cultured from either patients or donors have been used to successfully treat LSCD. In this review, some of the challenges and controversies associated with cultured LESC therapy will be discussed including alternative stem cell sources.

  14. Lasers, stem cells, and COPD

    PubMed Central

    2010-01-01

    The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed. PMID:20158898

  15. Immune privilege of stem cells.

    PubMed

    Ichiryu, Naoki; Fairchild, Paul J

    2013-01-01

    Immune privilege provides protection to vital tissues or cells of the body when foreign antigens are introduced into these sites. The modern concept of relative immune privilege applies to a variety of tissues and anatomical structures, including the hair follicles and mucosal surfaces. Even sites of chronic inflammation and developing tumors may acquire immune privilege by recruiting immunoregulatory effector cells. Adult stem cells are no exception. For their importance and vitality, many adult stem cell populations are believed to be immune privileged. A preimplantation-stage embryo that derives from a totipotent stem cell (i.e., a fertilized oocyte) must be protected from maternal allo-rejection for successful implantation and development to occur. Embryonic stem cells, laboratory-derived cell lines of preimplantation blastocyst-origin, may, therefore, retain some of the immunological properties of the developing embryo. However, embryonic stem cells and their differentiated tissue derivatives transplanted into a recipient do not necessarily have an ability to subvert immune responses to the extent required to exploit their pluripotency for regenerative medicine. In this review, an extended definition of immune privilege is developed and the capacity of adult and embryonic stem cells to display both relative and acquired immune privilege is discussed. Furthermore, we explore how these intrinsic properties of stem cells may one day be harnessed for therapeutic gain.

  16. On hematopoietic stem cell fate.

    PubMed

    Metcalf, Donald

    2007-06-01

    Multipotential hematopoietic stem cells (HSCs) maintain blood-cell formation throughout life. Here, Metcalf considers the origin and heterogeneity of HSCs, their ability to self-generate, and their commitment to the various hematopoietic lineages.

  17. Gastrointestinal stem cell up-to-date.

    PubMed

    Pirvulet, V

    2015-01-01

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

  18. Mesenchymal stem cells in regenerative rehabilitation

    PubMed Central

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-01-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future. PMID:27390452

  19. Mesenchymal stem cells in regenerative rehabilitation.

    PubMed

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-06-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient's medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future.

  20. A Comparison of Culture Characteristics between Human Amniotic Mesenchymal Stem Cells and Dental Stem Cells.

    PubMed

    Yusoff, Nurul Hidayat; Alshehadat, Saaid Ayesh; Azlina, Ahmad; Kannan, Thirumulu Ponnuraj; Hamid, Suzina Sheikh Abdul

    2015-04-01

    In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells.

  1. Germline and Pluripotent Stem Cells.

    PubMed

    Reik, Wolf; Surani, M Azim

    2015-11-02

    Epigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of the totipotent state, which in turn leads to the establishment of pluripotent cells in blastocysts. The latter are the cells from which pluripotent embryonic stem cells are derived and maintained in culture. Following blastocyst implantation, postimplantation epiblast cells develop, which give rise to all somatic cells as well as primordial germ cells, the precursors of sperm and eggs. Pluripotent stem cells in culture can be induced to undergo differentiation into somatic cells and germ cells in culture. Understanding the natural cycles of epigenetic reprogramming that occur in the germline will allow the generation of better and more versatile stem cells for both therapeutic and research purposes.

  2. Bone repair and stem cells.

    PubMed

    Ono, Noriaki; Kronenberg, Henry M

    2016-10-01

    Bones are an important component of vertebrates; they grow explosively in early life and maintain their strength throughout life. Bones also possess amazing capabilities to repair-the bone is like new without a scar after complete repair. In recent years, a substantial progress has been made in our understanding on mammalian bone stem cells. Mouse genetic models are powerful tools to understand the cell lineage, giving us better insights into stem cells that regulate bone growth, maintenance and repair. Recent findings about these stem cells raise new questions that require further investigations.

  3. Bone regeneration and stem cells

    PubMed Central

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  4. GPCRs in Stem Cell Function

    PubMed Central

    DOZE, VAN A.; PEREZ, DIANNE M.

    2013-01-01

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

  5. [Limbal stem cell deficiency management. A review].

    PubMed

    Kocaba, V; Damour, O; Auxenfans, C; Burillon, C

    2016-11-01

    Limbal stem cell deficiency is predominantly caused by severe eye burns resulting in a decreased or a complete ablation of the regenerative potential of these stem cells. The inability to reconstruct the corneal epithelium further leads conjunctivalization of the gimbal-epithelial barrier. These abnormalities collectively result in the progressive opacification of the cornea responsible for blindness that is driven by chronic corneal ulceration and neovascularization. The underlying pathology of the cornea affects the homeostasis of the neighboring conjunctiva, eyelids, and tear film. Therefore, the ocular reconstruction to treat limbal stem cell deficiency is quite prolonged and involves a continued treatment plan. The management of limbal stem cell deficiency has undergone a multitude of changes over the past several decades. The understanding of limbal anatomy and physiology, as well as therapeutic advances in the stem cell field have propelled the development of new treatments offering new hope to severely disabled patients. Cultivated limbal epithelial and oral mucosal epithelial transplantations are therefore viable alternatives that could be utilized for the treatment of limbal stem cell deficiency.

  6. Stem cell therapy without the cells

    PubMed Central

    Maguire, Greg

    2013-01-01

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

  7. Stem cells and combinatorial science.

    PubMed

    Fang, Yue Qin; Wong, Wan Qing; Yap, Yan Wen; Orner, Brendan P

    2007-09-01

    Stem cell-based technologies have the potential to help cure a number of cell degenerative diseases. Combinatorial and high throughput screening techniques could provide tools to control and manipulate the self-renewal and differentiation of stem cells. This review chronicles historic and recent progress in the stem cell field involving both pluripotent and multipotent cells, and it highlights relevant cellular signal transduction pathways. This review further describes screens using libraries of soluble, small-molecule ligands, and arrays of molecules immobilized onto surfaces while proposing future trends in similar studies. It is hoped that by reviewing both the stem cell and the relevant high throughput screening literature, this paper can act as a resource to the combinatorial science community.

  8. When size matters: differences in demineralized bone matrix particles affect collagen structure, mesenchymal stem cell behavior, and osteogenic potential.

    PubMed

    Dozza, B; Lesci, I G; Duchi, S; Della Bella, E; Martini, L; Salamanna, F; Falconi, M; Cinotti, S; Fini, M; Lucarelli, E; Donati, D

    2017-04-01

    Demineralized bone matrix (DBM) is a natural, collagen-based, osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM cytocompatibility and osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1-2 mm), medium (M, 0.5-1 mm), and small (S, <0.5 mm). After demineralization, the chemical-physical analysis clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. DBM-M displayed a preferable trend in almost all biological characteristics tested, although all DBM particles revealed an optimal cytocompatibility. Subcutaneous implantation of DBM particles into immunocompromised mice resulted in bone induction only for DBM-M. When sheep MSC were seeded onto particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. In conclusion, the collagen alteration in DBM-M is likely the best condition to promote bone induction in vivo. Furthermore, the choice of 0.5-1 mm particles may enable to obtain more efficient and consistent results among different research groups in bone tissue-engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1019-1033, 2017.

  9. Different outcomes of allogeneic hematopoietic stem cell transplant in a pair of twins affected by juvenile myelomonocytic leukemia.

    PubMed

    Cesaro, Simone; De Filippi, Paola; Di Meglio, Annamaria; Leszl, Anna; Donska, Svetlana; Zaccaron, Ada; Cagioni, Claudia; Galavotti, Roberta; Danesino, Cesare; Aprili, Fiorenza; Cugno, Chiara; te Kronnie, Geertruy; Zecca, Marco; Bresolin, Silvia

    2014-02-01

    A twin pair affected by juvenile myelomonocytic leukemia (JMML) with the same somatic PTPN11 mutation and abnormal chromosome 7 in bone marrow samples but distinct prognostic gene expression signatures, received a matched-unrelated donor and matched-unrelated cord blood transplant, respectively. Both twins fully engrafted, but after 6 months, the twin with an acute-myeloid-like (AML-like) signature at diagnosis rejected the graft and had an autologous reconstitution. A second transplant with an unrelated 5/6-HLA-matched-loci cord blood performed after 4 months from rejection was unsuccessful. After 25 months from diagnosis, the twin with the AML-like gene expression signature died of liver failure while on progression of his JMML. The other twin, who had a non-acute-myeloid-like (non-AML-like) gene expression signature at diagnosis is in complete hematological remission with full donor chimera. This observation suggests a biological diversity of JMML also in patients with a common genetic background.

  10. Stem Cells in the Lung

    PubMed Central

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

    2007-01-01

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

  11. Dental stem cells and their sources.

    PubMed

    Sedgley, Christine M; Botero, Tatiana M

    2012-07-01

    The search for more accessible mesenchymal stem cells than those found in bone marrow has propelled interest in dental tissues. Human dental stem/progenitor cells (collectively termed dental stem cells [DSCs]) that have been isolated and characterized include dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, periodontal ligament stem cells, and dental follicle progenitor cells. Common characteristics of these cell populations are the capacity for self-renewal and the ability to differentiate into multiple lineages. In vitro and animal studies have shown that DSCs can differentiate into osseous, odontogenic, adipose, endothelial, and neural-like tissues.

  12. Modeling Stem Cell Myogenic Differentiation

    PubMed Central

    Deshpande, Rajiv S.; Spector, Alexander A.

    2017-01-01

    The process of stem cell myogenesis (transformation into skeletal muscle cells) includes several stages characterized by the expression of certain combinations of myogenic factors. The first part of this process is accompanied by cell division, while the second part is mainly associated with direct differentiation. The mechanical cues are known to enhance stem cell myogenesis, and the paper focuses on the stem cell differentiation under the condition of externally applied strain. The process of stem cell myogenic differentiation is interpreted as the interplay among transcription factors, targeted proteins and strain-generated signaling molecule, and it is described by a kinetic multi-stage model. The model parameters are optimally adjusted by using the available data from the experiment with adipose-derived stem cells subjected to the application of cyclic uniaxial strains of the magnitude of 10%. The modeling results predict the kinetics of the process of myogenic differentiation, including the number of cells in each stage of differentiation and the rates of differentiation from one stage to another for different strains from 4% to 16%. The developed model can help better understand the process of myogenic differentiation and the effects of mechanical cues on stem cell use in muscle therapies. PMID:28106095

  13. Diabetes and Stem Cell Function

    PubMed Central

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

    2015-01-01

    Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer's disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment. PMID:26075247

  14. Stem cell therapy for Parkinson's disease.

    PubMed

    Takahashi, Jun

    2007-06-01

    The aim of stem cell therapy for Parkinson's disease is to reconstruct nigro-striatal neuronal pathways using endogenous neural stem/precursor cells or grafted dopaminergic neurons. As an alternative, transplantation of stem cell-derived dopaminergic neurons into the striatum has been attempted, with the aim of stimulating local synapse formation and/or release of dopamine and cytokines from grafted cells. Candidate stem cells include neural stem/precursor cells, embryonic stem cells and other stem/precursor cells. Among these, embryonic stem cells are pluripotent cells that proliferate extensively, making them a good potential donor source for transplantation. However, tumor formation and ethical issues present major problems for embryonic stem cell therapy. This review describes the current status of stem cell therapy for Parkinson's disease, as well as future research approaches from a clinical perspective.

  15. Brain stem slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture.

    PubMed

    Kaiser, Andreas; Kale, Ajay; Novozhilova, Ekaterina; Siratirakun, Piyaporn; Aquino, Jorge B; Thonabulsombat, Charoensri; Ernfors, Patrik; Olivius, Petri

    2014-05-30

    Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve.

  16. Vascular potential of human pluripotent stem cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cardiovascular disease is the number one cause of death and disability in the US. Understanding the biological activity of stem and progenitor cells, and their ability to contribute to the repair, regeneration and remodeling of the heart and blood vessels affected by pathological processes is an ess...

  17. Improving Cell Engraftment in Cardiac Stem Cell Therapy

    PubMed Central

    Xie, Xiaoyun

    2016-01-01

    Myocardial infarction (MI) affects millions of people worldwide. MI causes massive cardiac cell death and heart function decrease. However, heart tissue cannot effectively regenerate by itself. While stem cell therapy has been considered an effective approach for regeneration, the efficacy of cardiac stem cell therapy remains low due to inferior cell engraftment in the infarcted region. This is mainly a result of low cell retention in the tissue and poor cell survival under ischemic, immune rejection and inflammatory conditions. Various approaches have been explored to improve cell engraftment: increase of cell retention using biomaterials as cell carriers; augmentation of cell survival under ischemic conditions by preconditioning cells, genetic modification of cells, and controlled release of growth factors and oxygen; and enhancement of cell survival by protecting cells from excessive inflammation and immune surveillance. In this paper, we review current progress, advantages, disadvantages, and potential solutions of these approaches. PMID:26783405

  18. Neural Stem Cells and Glioblastoma

    PubMed Central

    Rispoli, Rossella; Conti, Carlo; Celli, Paolo; Caroli, Emanuela; Carletti, Sandro

    2014-01-01

    Summary Glioblastoma multiforme represents one of the most common brain cancers with a rather heterogeneous cellular composition, as indicated by the term “multiforme". Recent reports have described the isolation and identification of cancer neural stem cells from human adult glioblastoma multiforme, which possess the capacity to establish, sustain, and expand these tumours, even under the challenging settings posed by serial transplantation experiments. Our study focused on the distribution of neural cancer stem cells inside the tumour. The study is divided into three phases: removal of tumoral specimens in different areas of the tumour (centre, periphery, marginal zone) in an operative room equipped with a 1.5 T scanner; isolation and characterization of neural cancer stem cells from human adult glioblastoma multiforme; identification of neural cancer stem cell distribution inside the tumour. PMID:24750704

  19. Stem cells, tissue engineering and periodontal regeneration.

    PubMed

    Han, J; Menicanin, D; Gronthos, S; Bartold, P M

    2014-06-01

    The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.

  20. [Progress in stem cells and regenerative medicine].

    PubMed

    Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

    2015-06-01

    Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

  1. Tracking stem cells in the cardiovascular system.

    PubMed

    Chemaly, Elie R; Yoneyama, Ryuichi; Frangioni, John V; Hajjar, Roger J

    2005-11-01

    Stem cells are a promising approach to cardiovascular therapeutics. Animal experiments have assessed the fate of injected stem cells through ex vivo methods on sacrificed animals. Approaches are needed for in vivo tracking of stem cells. Various imaging techniques and contrast agents for stem cell tracking will be reviewed.

  2. Immunotargeting of cancer stem cells

    PubMed Central

    Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

    2015-01-01

    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

  3. Stem cell potential of the mammalian gonad

    PubMed Central

    Liu, Chia-Feng; Barsoum, Ivraym; Gupta, Rupesh; Hofmann, Marie-Claude; Yao, Humphrey Hung-Chang

    2010-01-01

    Stem cells have enormous potential for therapeutic application because of their ability to self-renew and differentiate into different cell types. Gonads, which consist of somatic cells and germ cells, are the only organs capable of transmitting genetic materials to the offspring. Germ-line stem cells and somatic stem cells have been found in the testis; however, the presence of stem cells in the ovary remains controversial. In this review, we discuss studies focusing on whether stem cell properties are present in the different cell types of male and female gonads and their implications on stem cell research. PMID:19482665

  4. Stem cell applications in diabetes.

    PubMed

    Noguchi, Hirofumi

    2012-01-01

    Diabetes mellitus is a devastating disease and the World Health Organization (WHO) expects that the number of diabetic patients will increase to 300 million by the year 2025. Patients with diabetes experience decreased insulin secretion that is linked to a significant reduction in the number of islet cells. Type 1 diabetes is characterized by the selective destruction of pancreatic β cells caused by an autoimmune attack. Type 2 diabetes is a more complex pathology that, in addition to β cell loss caused by apoptotic programs, includes β cell de-differentiation and peripheric insulin resistance. The success achieved over the last few years with islet transplantation suggests that diabetes can be cured by the replenishment of deficient β cells. These observations are proof of the concept and have intensified interest in treating diabetes or other diseases not only by cell transplantation but also by stem cells. An increasing body of evidence indicates that, in addition to embryonic stem cells, several potential adult stem/progenitor cells derived from the pancreas, liver, spleen, and bone marrow could differentiate into insulin-producing cells in vitro or in vivo. However, significant controversy currently exists in this field. Pharmacological approaches aimed at stimulating the in vivo/ex vivo regeneration of β cells have been proposed as a way of augmenting islet cell mass. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. A new technology, known as protein transduction, facilitates the differentiation of stem cells into insulin-producing cells. Recent progress in the search for new sources of β cells has opened up several possibilities for the development of new treatments for diabetes.

  5. New Insights into Thyroid Stem Cells

    PubMed Central

    Lin, Reigh-Yi

    2009-01-01

    Stem cells exhibit an extraordinary ability for self-renewal. They also give rise to many specialized cells. The potential of stem cells in regenerative medicine, developmental biology, and drug discovery has been well documented. Although advances in stem cell science have raised broad ethical concerns, it is clear that stem cell technology has revolutionized our thinking in modern biology and medicine and provided the basis for understanding many of the mechanisms controlling basic biological processes and disease mechanisms. This review details the nascent field of thyroid stem cell research, exploring the current status of thyroid stem cell differentiation from the perspectives of both developmental biology and cell replacement therapy. It highlights successes to date in the generation of thyroid follicular cells from embryonic stem cells in the laboratory and the identification and characterization of adult stem cells from human thyroid glands and thyroid cancers. Finally, it outlines future challenges with a focus on potential stem cell therapy for thyroid patients. PMID:17727339

  6. Stem Cells and Liver Regeneration

    PubMed Central

    DUNCAN, ANDREW W.; DORRELL, CRAIG; GROMPE, MARKUS

    2011-01-01

    One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition. PMID:19470389

  7. Coculture with embryonic stem cells improves neural differentiation of adipose tissue-derived stem cells.

    PubMed

    Bahmani, L; Taha, M F; Javeri, A

    2014-07-11

    Embryonic stem (ES) cells secrete some soluble factors which may affect the differentiation potential of adult stem cells toward different lineages. In the present study, we evaluated neural differentiation of mouse adipose tissue-derived stem cells (ADSCs) following coculture with ES cells. For this purpose, ADSCs were induced in a medium supplemented with a synthetic serum replacement and various concentrations of retinoic acid (RA). Then, third-passaged ADSCs were indirectly cocultured with ES cells, and the expression levels of pluripotency markers, OCT4 and Sox2, mesenchymal stem cell markers, CD73 and CD105, and proliferating cell nuclear antigen (PCNA), were assessed in the cocultured ADSCs. Moreover, the control and cocultured ADSCs were differentiated with or without RA treatment. We showed here that 2-week differentiated ADSCs expressed several neuron-specific genes, and RA treatment improved neural differentiation of the ADSCs. The expression levels of OCT4, Sox2 and PCNA were upregulated in the cocultured ADSCs. Moreover, coculture with the ES cells significantly improved neural differentiation of the ADSCs. Treatment of the cocultured ADSCs with RA diminished the expression of neural maturation markers. Coculture with the ES cells efficiently improves neural differentiation of the ADSCs. Non-contact coculture with the ES cells may be used as an efficient strategy to improve differentiation potential of adult stem cells for developmental studies and regenerative medicine.

  8. Stem cells in pediatric cardiology.

    PubMed

    Patel, Pranali; Mital, Seema

    2013-10-01

    The ability to reprogram virtually any cell of human origin to behave like embryonic or pluripotent stem cells is a major breakthrough in stem cell biology. Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study "disease in a dish" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. They also provide an exciting opportunity for drug discovery and drug repurposing for disorders with a known molecular basis including childhood onset heart disease, particularly cardiac genetic disorders. The review will discuss their use in drug discovery, efficacy and toxicity studies with emphasis on challenges in pediatric-focused drug discovery. Issues that will need to be addressed in the coming years include development of maturation protocols for iPSC-derived cardiac lineages, use of iPSCs to study not just cardiac but extra-cardiac phenotypes in the same patient, scaling up of stem cell platforms for high-throughput drug screens, translating drug testing results to clinical applications in the paradigm of personalized medicine, and improving both the efficiency and the safety of iPSC-derived lineages for future stem cell therapies.

  9. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors

    SciTech Connect

    Maroni, Paola; Brini, Anna Teresa; Arrigoni, Elena; Girolamo, Laura de; Niada, Stefania; Matteucci, Emanuela; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Acetylation affected hASCs osteodifferentiation through Runx2-PPAR{gamma}. Black-Right-Pointing-Pointer HDACs knocking-down favoured the commitment effect of osteogenic medium. Black-Right-Pointing-Pointer HDACs silencing early activated Runx2 and ALP. Black-Right-Pointing-Pointer PPAR{gamma} reduction and calcium/collagen deposition occurred later. Black-Right-Pointing-Pointer Runx2/PPAR{gamma} target genes were modulated in line with HDACs role in osteo-commitment. -- Abstract: The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) {gamma}. These key osteogenic and adipogenic transcription factors are oppositely involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPAR{gamma} and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPAR{gamma}/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPAR{gamma} target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal

  10. [Therapeutic use of stem cells].

    PubMed

    Uzan, Georges

    2004-09-15

    Stem cells display important capacities of self renewing, proliferation and differentiation. Because those present in the embryo have the more remarkable properties, their potential use in the therapy of until now incurable degenerative diseases have been envisioned. Embryonic stem (ES) cells are located in the inner mass of the balstocyst at early stages of the development. Even in long-term cultures they still retain their undifferentiated features. Under specific culture conditions, ES cells can be committed into a variety of differentiation pathways, giving rise to large amounts of cells corresponding to different tissues (neurones, cardiomyocytes, skeletal muscle, etc.). However, producing these tissues from already established ES cell lines would lead to immune rejection when transplanted to patients. To prevent this pitfall and using the expertise accumulated by animal cloning by nucleus transfer, it has been proposed to adapt this technique to human ES cells. The therapeutic cloning consists in transferring the nucleus of somatic stem cells isolated from the patient into an enucleated oocyte, to allow blastocyst development from which ES cells will be derived. From these stem cells, compatible tissues will be then produced. The problem is that it is in theoretically possible to reimplant the cloned blastocyst into a surrogate mother for obtaining a baby genetically identical to the donor. This is called reproductive cloning. This worrying risk raises important ethic and legal questions.

  11. Inflammation Shapes Stem Cells and Stemness during Infection and Beyond

    PubMed Central

    Michael, Stella; Achilleos, Charis; Panayiotou, Theofano; Strati, Katerina

    2016-01-01

    The outcome of an inflammatory incident can hang in the balance between restoring health and tissue integrity on the one hand, and promoting aberrant tissue homeostasis and adverse outcomes on the other. Both microbial-related and sterile inflammation is a complex response characterized by a range of innate immune cell types, which produce and respond to cytokine mediators and other inflammatory signals. In turn, cells native to the tissue in question can sense these mediators and respond by migrating, proliferating and regenerating the tissue. In this review we will discuss how the specific outcomes of inflammatory incidents are affected by the direct regulation of stem cells and cellular plasticity. While less well appreciated than the effects of inflammatory signals on immune cells and other differentiated cells, the effects are crucial in understanding inflammation and appropriately managing therapeutic interventions. PMID:27853732

  12. Epigenetics in cancer stem cells.

    PubMed

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  13. Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture

    SciTech Connect

    Wei, Yan; Li, Yuan; Chen, Chao; Stoelzel, Katharina; Kaufmann, Andreas M.

    2011-04-15

    Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of cells from human skeletal muscle that is able to proliferate for extended periods of time as floating clusters of rounded cells, termed 'myospheres' or myosphere-derived progenitor cells (MDPCs). The phenotypic characteristics and functional properties of these cells were determined using reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunocytochemistry. Our results showed that these cells are clonogenic, express skeletal progenitor cell markers Pax7, ALDH1, Myod, and Desmin and the stem cell markers Nanog, Sox2, and Oct3/4 significantly elevated over controls. They could be maintained proliferatively active in vitro for more than 20 weeks and passaged at least 18 times, despite an average donor-age of 63 years. Individual clones (4.2%) derived from single cells were successfully expanded showing clonogenic potential and sustained proliferation of a subpopulation in the myospheres. Myosphere-derived cells were capable of spontaneous differentiation into myotubes in differentiation media and into other mesodermal cell lineages in induction media. We demonstrate here that direct culture and expansion of stem cells from human skeletal muscle is straightforward and reproducible with the appropriate technique. These cells may provide a viable resource of adult stem cells for future therapies of disease affecting skeletal muscle or mesenchymal lineage derived cell types.

  14. Ocular Stem Cell Research from Basic Science to Clinical Application: A Report from Zhongshan Ophthalmic Center Ocular Stem Cell Symposium

    PubMed Central

    Ouyang, Hong; Goldberg, Jeffrey L.; Chen, Shuyi; Li, Wei; Xu, Guo-Tong; Li, Wei; Zhang, Kang; Nussenblatt, Robert B.; Liu, Yizhi; Xie, Ting; Chan, Chi-Chao; Zack, Donald J.

    2016-01-01

    Stem cells hold promise for treating a wide variety of diseases, including degenerative disorders of the eye. The eye is an ideal organ for stem cell therapy because of its relative immunological privilege, surgical accessibility, and its being a self-contained system. The eye also has many potential target diseases amenable to stem cell-based treatment, such as corneal limbal stem cell deficiency, glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa (RP). Among them, AMD and glaucoma are the two most common diseases, affecting over 200 million people worldwide. Recent results on the clinical trial of retinal pigment epithelial (RPE) cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) in treating dry AMD and Stargardt’s disease in the US, Japan, England, and China have generated great excitement and hope. This marks the beginning of the ocular stem cell therapy era. The recent Zhongshan Ophthalmic Center Ocular Stem Cell Symposium discussed the potential applications of various stem cell types in stem cell-based therapies, drug discoveries and tissue engineering for treating ocular diseases. PMID:27102165

  15. Stem cells' exodus: a journey to immortality.

    PubMed

    Zhou, Yi; Lewallen, Michelle; Xie, Ting

    2013-01-28

    Stem cell niches provide a regulatory microenvironment that retains stem cells and promotes self-renewal. Recently in Developmental Cell, Rinkevich et al. (2013) showed that cell islands (CIs) of Botryllus schlosseri, a colonial chordate, provide niches for maintaining cycling stem cells that migrate from degenerated CIs to newly formed buds.

  16. Nutritional regulation of stem and progenitor cells in Drosophila

    PubMed Central

    Shim, Jiwon; Gururaja-Rao, Shubha; Banerjee, Utpal

    2013-01-01

    Stem cells and their progenitors are maintained within a microenvironment, termed the niche, through local cell-cell communication. Systemic signals originating outside the niche also affect stem cell and progenitor behavior. This review summarizes studies that pertain to nutritional effects on stem and progenitor cell maintenance and proliferation in Drosophila. Multiple tissue types are discussed that utilize the insulin-related signaling pathway to convey nutritional information either directly to these progenitors or via other cell types within the niche. The concept of systemic control of these cell types is not limited to Drosophila and may be functional in vertebrate systems, including mammals. PMID:24255094

  17. Stem cell therapy for Alzheimer's disease.

    PubMed

    Abdel-Salam, Omar M E

    2011-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder which impairs the memory and intellectual abilities of the affected individuals. Loss of episodic as well as semantic memory is an early and principal feature. The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process. Extracellular as well as intracellular deposition of beta-amyloid or Abeta (Abeta) protein, intracellular formation of neurofibrillary tangles and neuronal loss are the neuropathological hallmarks of AD. In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems. Stem cells obtained from embryonic as well as adult tissue and grafted into the intact brain of mice or rats were mostly followed by their incorporation into the host parenchyma and differentiation into functional neural lineages. In the lesioned brain, stem cells exhibited targeted migration towards the damaged regions of the brain, where they engrafted, proliferated and matured into functional neurones. Neural precursor cells can be intravenously administered and yet migrate into brain damaged areas and induce functional recovery. Observations in animal models of AD have provided evidence that transplanted stem cells or neural precursor cells (NPCs) survive, migrate, and differentiate into cholinergic neurons, astrocytes, and oligodendrocytes with amelioration of the learning/memory deficits. Besides replacement of lost or damaged cells, stem cells stimulate endogenous neural precursors, enhance structural neuroplasticity, and down regulate proinflammatory cytokines and neuronal apoptotic death. Stem cells could also be genetically modified to express growth factors into the brain. In the last years, evidence indicated that the adult brain of mammals preserves the capacity to generate new neurons from neural stem/progenitor cells. Inefficient adult neurogenesis may contribute to the

  18. Stem-cell ecology and stem cells in motion

    PubMed Central

    Scadden, David T.

    2008-01-01

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

  19. Common stemness regulators of embryonic and cancer stem cells

    PubMed Central

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies. PMID:26516408

  20. Introduction to stem cells and regenerative medicine.

    PubMed

    Kolios, George; Moodley, Yuben

    2013-01-01

    Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent). There are several sources of stem cells with varying potencies. Pluripotent cells are embryonic stem cells derived from the inner cell mass of the embryo and induced pluripotent cells are formed following reprogramming of somatic cells. Pluripotent cells can differentiate into tissue from all 3 germ layers (endoderm, mesoderm, and ectoderm). Multipotent stem cells may differentiate into tissue derived from a single germ layer such as mesenchymal stem cells which form adipose tissue, bone, and cartilage. Tissue-resident stem cells are oligopotent since they can form terminally differentiated cells of a specific tissue. Stem cells can be used in cellular therapy to replace damaged cells or to regenerate organs. In addition, stem cells have expanded our understanding of development as well as the pathogenesis of disease. Disease-specific cell lines can also be propagated and used in drug development. Despite the significant advances in stem cell biology, issues such as ethical controversies with embryonic stem cells, tumor formation, and rejection limit their utility. However, many of these limitations are being bypassed and this could lead to major advances in the management of disease. This review is an introduction to the world of stem cells and discusses their definition, origin, and classification, as well as applications of these cells in regenerative medicine.

  1. Stem cell therapy for treatment of epilepsy.

    PubMed

    Goodarzi, Parisa; Aghayan, Hamid Reza; Soleimani, Masoud; Norouzi-Javidan, Abbas; Mohamadi-Jahani, Fereshteh; Jahangiri, Sharareh; Emami-Razavi, Seyed Hasan; Larijani, Bagher; Arjmand, Babak

    2014-01-01

    Epilepsy as one of the most common neurological disorders affects more than 50 million people worldwide with a higher prevalence rate in low-income countries. Excessive electrical discharges in neurons following neural cell damage or loss cause recurrent seizures. One of the most common and difficult to treat types of epilepsy is temporal lobe epilepsy (TLE) which results from hippocampal sclerosis. Nowadays, similar to other diseases, epilepsy also is a candidate for treatment with different types of stem cells. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. Two major roles of stem cell therapy in epilepsy are prophylaxis against chronic epilepsy and amelioration cognitive function after the occurrence of TLE. Several animal studies have supported the use of these cells for treating drug-resistant TLE. Although stem cell therapy seems like a promising approach for treatment of epilepsy in the future however, there are some serious safety and ethical concerns that are needed to be eliminated before clinical application.

  2. Multipotent Stem Cell and Current Application.

    PubMed

    Sobhani, Aligholi; Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sargolzaei Aval, Fereydoon

    2017-01-01

    Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. Multipotent Stem cells have been applying in treatment of different disorders such as spinal cord injury, bone fracture, autoimmune diseases, rheumatoid arthritis, hematopoietic defects, and fertility preservation.

  3. Stem cell cultivation in bioreactors.

    PubMed

    Rodrigues, Carlos A V; Fernandes, Tiago G; Diogo, Maria Margarida; da Silva, Cláudia Lobato; Cabral, Joaquim M S

    2011-01-01

    Cell-based therapies have generated great interest in the scientific and medical communities, and stem cells in particular are very appealing for regenerative medicine, drug screening and other biomedical applications. These unspecialized cells have unlimited self-renewal capacity and the remarkable ability to produce mature cells with specialized functions, such as blood cells, nerve cells or cardiac muscle. However, the actual number of cells that can be obtained from available donors is very low. One possible solution for the generation of relevant numbers of cells for several applications is to scale-up the culture of these cells in vitro. This review describes recent developments in the cultivation of stem cells in bioreactors, particularly considerations regarding critical culture parameters, possible bioreactor configurations, and integration of novel technologies in the bioprocess development stage. We expect that this review will provide updated and detailed information focusing on the systematic production of stem cell products in compliance with regulatory guidelines, while using robust and cost-effective approaches.

  4. Stem cells in orthopaedics and fracture healing.

    PubMed

    Alwattar, Basil J; Schwarzkopf, Ran; Kirsch, Thorsten

    2011-01-01

    Stem cell application is a burgeoning field of medicine that is likely to influence the future of orthopaedic surgery. Stem cells are associated with great promise and great controversy. For the orthopaedic surgeon, stem cells may change the way that orthopaedic surgery is practiced and the overall approach of the treatment of musculoskeletal disease. Stem cells may change the field of orthopaedics from a field dominated by surgical replacements and reconstructions to a field of regeneration and prevention. This review will introduce the basic concepts of stem cells pertinent to the orthopaedic surgeon and proceed with a more in depth discussion of current developments in the study of stem cells in fracture healing.

  5. Diffusion tensor imaging as a biomarker for assessing neuronal stem cell treatments affecting areas distal to the site of spinal cord injury.

    PubMed

    Jirjis, Michael B; Valdez, Chris; Vedantam, Aditya; Schmit, Brian D; Kurpad, Shekar N

    2017-02-01

    OBJECTIVE The aims of this study were to determine if the morphological and functional changes induced by neural stem cell (NSC) grafts after transplantation into the rodent spinal cord can be detected using MR diffusion tensor imaging (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be a biomarker for cell transplantation in spinal cord injury (SCI). METHODS A spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley rats that were separated into 4 groups, including a sham group (injury without NSC injection), NSC control group (injury with saline injection), co-injection control group (injury with Prograf), and the experimental group (injury with NSC and Prograf injection). The NSC injection was completed 1 week after injury into the site of injury and the rats in the experimental group were compared to the rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a 9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical spinal cord from the sham surgery, injury with saline injection, injury with injection of Prograf only, and injury with C17.2 NSC and Prograf injection were examined to evaluate if cellular proliferation induced by intrathoracic C17.2 engraftment was detectable in a noninvasive manner. RESULTS At 5 weeks after injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial diffusion (RD) coefficients, and MD of water (average of the RD and LD eigenvalues in the stem cell line-treated group) increased to an average of 1.44 × 10(-3) sec/mm(2) in the cervical segments, while the control groups averaged 0.98 × 10(-3) s/mm(2). Post hoc Tukey's honest significant difference tests demonstrated that the transplanted stem cells had significantly higher MD values than the other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks displayed

  6. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  7. Adult stem cell therapy: dream or reality?

    PubMed

    Moraleda, Jose M; Blanquer, Miguel; Bleda, Patricia; Iniesta, Paqui; Ruiz, Francisco; Bonilla, Sonia; Cabanes, Carmen; Tabares, Lucía; Martinez, Salvador

    2006-12-01

    Adult stem cells may be an invaluable source of plastic cells for tissue regeneration. The bone marrow contains different subpopulations of adult stem cells easily accessible for transplantation. However the therapeutic value of adult stem cell is a question of debate in the scientific community. We have investigated the potential benefits of adult hematopoietic stem cell transplantation in animal models of demyelinating and motor neuron diseases. Our results suggest that transplantation of HSC have direct and indirect neuroregenerative and neuroprotective effects.

  8. Prospect of Human Pluripotent Stem Cell-Derived Neural Crest Stem Cells in Clinical Application

    PubMed Central

    Zhu, Qian; Lu, Qiqi; Gao, Rong

    2016-01-01

    Neural crest stem cells (NCSCs) represent a transient and multipotent cell population that contributes to numerous anatomical structures such as peripheral nervous system, teeth, and cornea. NCSC maldevelopment is related to various human diseases including pigmentation abnormalities, disorders affecting autonomic nervous system, and malformations of teeth, eyes, and hearts. As human pluripotent stem cells including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can serve as an unlimited cell source to generate NCSCs, hESC/hiPSC-derived NCSCs can be a valuable tool to study the underlying mechanisms of NCSC-associated diseases, which paves the way for future therapies for these abnormalities. In addition, hESC/hiPSC-derived NCSCs with the capability of differentiating to various cell types are highly promising for clinical organ repair and regeneration. In this review, we first discuss NCSC generation methods from human pluripotent stem cells and differentiation mechanism of NCSCs. Then we focus on the clinical application potential of hESC/hiPSC-derived NCSCs on peripheral nerve injuries, corneal blindness, tooth regeneration, pathological melanogenesis, Hirschsprung disease, and cardiac repair and regeneration. PMID:28090209

  9. Human fetal mesenchymal stem cells.

    PubMed

    O'Donoghue, Keelin; Chan, Jerry

    2006-09-01

    Stem cells have been isolated at all stages of development from the early developing embryo to the post-reproductive adult organism. However, the fetal environment is unique as it is the only time in ontogeny that there is migration of stem cells in large numbers into different organ compartments. While fetal neural and haemopoietic stem cells (HSC) have been well characterised, only recently have mesenchymal stem cells from the human fetus been isolated and evaluated. Our group have characterised in human fetal blood, liver and bone marrow a population of non-haemopoietic, non-endothelial cells with an immunophenotype similar to adult bone marrow-derived mesenchymal stem cells (MSC). These cells, human fetal mesenchymal stem cells (hfMSC), are true multipotent stem cells with greater self-renewal and differentiation capacity than their adult counterparts. They circulate in first trimester fetal blood and have been found to traffic into the maternal circulation, engrafting in bone marrow, where they remain microchimeric for decades after pregnancy. Though fetal microchimerism has been implicated in the pathogenesis of autoimmune disease, the biological role of hfMSC microchimerism is unknown. Potential downstream applications of hfMSC include their use as a target cell for non-invasive pre-natal diagnosis from maternal blood, and for fetal cellular and gene therapy. Using hfMSC in fetal therapy offers the theoretical advantages of avoidance of immune rejection, increased engraftment, and treatment before disease pathology sets in. Aside from allogeneic hfMSC in utero transplantation, the use of autologous hfMSC has been brought a step forward with the development of early blood sampling techniques, efficient viral transduction and clonal expansion. Work is ongoing to determine hfMSC fate post-transplantation in murine models of genetic disease. In this review we will examine what is known about hfMSC biology, as well as discussing areas for future research. The

  10. Emerging molecular approaches in stem cell biology.

    PubMed

    Jaishankar, Amritha; Vrana, Kent

    2009-04-01

    Stem cells are characterized by their ability to self-renew and differentiate into multiple adult cell types. Although substantial progress has been made over the last decade in understanding stem cell biology, recent technological advances in molecular and systems biology may hold the key to unraveling the mystery behind stem cell self-renewal and plasticity. The most notable of these advances is the ability to generate induced pluripotent cells from somatic cells. In this review, we discuss our current understanding of molecular similarities and differences among various stem cell types. Moreover, we survey the current state of systems biology and forecast future needs and direction in the stem cell field.

  11. Notch signaling regulates gastric antral LGR5 stem cell function.

    PubMed

    Demitrack, Elise S; Gifford, Gail B; Keeley, Theresa M; Carulli, Alexis J; VanDussen, Kelli L; Thomas, Dafydd; Giordano, Thomas J; Liu, Zhenyi; Kopan, Raphael; Samuelson, Linda C

    2015-10-14

    The major signaling pathways regulating gastric stem cells are unknown. Here we report that Notch signaling is essential for homeostasis of LGR5(+) antral stem cells. Pathway inhibition reduced proliferation of gastric stem and progenitor cells, while activation increased proliferation. Notch dysregulation also altered differentiation, with inhibition inducing mucous and endocrine cell differentiation while activation reduced differentiation. Analysis of gastric organoids demonstrated that Notch signaling was intrinsic to the epithelium and regulated growth. Furthermore, in vivo Notch manipulation affected the efficiency of organoid initiation from glands and single Lgr5-GFP stem cells, suggesting regulation of stem cell function. Strikingly, constitutive Notch activation in LGR5(+) stem cells induced tissue expansion via antral gland fission. Lineage tracing using a multi-colored reporter demonstrated that Notch-activated stem cells rapidly generate monoclonal glands, suggesting a competitive advantage over unmanipulated stem cells. Notch activation was associated with increased mTOR signaling, and mTORC1 inhibition normalized NICD-induced increases in proliferation and gland fission. Chronic Notch activation induced undifferentiated, hyper-proliferative polyps, suggesting that aberrant activation of Notch in gastric stem cells may contribute to gastric tumorigenesis.

  12. Development of bioengineering system for stem cell proliferation

    NASA Astrophysics Data System (ADS)

    Park, H. S.; Shah, R.; Shah, C.

    2016-08-01

    From last decades, intensive research in the field of stem cells proliferation had been promoted due to the unique property of stem cells to self-renew themselves into multiples and has potential to replicate into an organ or tissues and so it's highly demanding though challenging. Bioreactor, a mechanical device, works as a womb for stem cell proliferation by providing nutritious environment for the proper growth of stem cells. Various factors affecting stem cells growth are the bioreactor mechanism, feeding of continuous nutrients, healthy environment, etc., but it always remains a challenge for controlling biological parameters. The present paper unveils the design of mechanical device commonly known as bioreactor in tissues engineering and biotech field, use for proliferation of stem cells and imparts the proper growing condition for stem cells. This high functional bioreactor provides automation mixing of cell culture and stem cells. This design operates in conjunction with mechanism of reciprocating motion. Compare to commercial bioreactors, this proposed design is more convenient, easy to operate and less maintenance is required as bioreactor culture bag is made of polyethylene which is single use purpose. Development of this bioengineering system will be beneficial for better growth and expansion of stem cell

  13. Mesenchymal Stem Cells as Therapeutics

    PubMed Central

    Parekkadan, Biju; Milwid, Jack M.

    2013-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID:20415588

  14. Ethics and Governance of Stem Cell Banks.

    PubMed

    Chalmers, Donald; Rathjen, Peter; Rathjen, Joy; Nicol, Dianne

    2017-01-01

    This chapter examines the ethical principles and governance frameworks for stem cell banks. Good governance of stem cell banks should balance facilitation of the clinical use of stem cells with the proper respect and protection of stem cell sample providers and stem cell recipients and ensure compliance with national regulatory requirements to foster public trust in the use of stem cell technology. Stem cell banks must develop with regard to the science, the needs of scientists, and the requirements of the public, which will benefit from this science. Given the international reach of this promising research and its clinical application, it is necessary for stem cell bank governance frameworks to be harmonized across jurisdictions.

  15. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  16. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  17. Can Stem Cell 'Patch' Help Heart Failure?

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_164475.html Can Stem Cell 'Patch' Help Heart Failure? Small improvement seen over ... Scientists report another step in the use of stem cells to help treat people with debilitating heart failure. ...

  18. Stem cell technology for neurodegenerative diseases.

    PubMed

    Lunn, J Simon; Sakowski, Stacey A; Hur, Junguk; Feldman, Eva L

    2011-09-01

    Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

  19. Modeling Stem Cell Induction Processes

    PubMed Central

    Grácio, Filipe; Cabral, Joaquim; Tidor, Bruce

    2013-01-01

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

  20. [Genetic regulation of plant shoot stem cells].

    PubMed

    Al'bert, E V; Ezhova, T A

    2013-02-01

    This article describes the main features of plant stem cells and summarizes the results of studies of the genetic control of stem cell maintenance in the apical meristem of the shoot. It is demonstrated that the WUS-CLV gene system plays a key role in the maintenance of shoot apical stem cells and the formation of adventitious buds and somatic embryos. Unconventional concepts of plant stem cells are considered.

  1. Mobilization of peripheral blood stem cells.

    PubMed

    Arslan, Onder; Moog, Rainer

    2007-10-01

    The use of peripheral blood stem cells (PBSC) as a source of hematopoietic stem cells is steadily increasing and has nearly supplanted bone marrow transplantation. The present article reviews mobilization of PBSC as well as the side effects. Under steady state conditions less than 0.05% of the white blood cells (WBC) are CD34+ cells. Chemotherapy results in a 5-15-fold increase of PBSC. Combining chemotherapy and growth factors increases CD34+ cells up to 6% of WBC. In the allogeneic setting, granulocyte-colony stimulating factor (G-CSF) is used alone for PBSC mobilization. Several factors affect the mobilization of PBSC: age, gender, type of growth factor, dose of the growth factor and in the autologous setting, the patient's diagnosis, chemotherapy regimen and number of previous chemotherapy cycles or radiation. Muscle and bone pain are frequent adverse events in allogeneic stem cell mobilization but are usually tolerated with the use of analgesics. Spleen enlargement followed by rupture is a serious complication in allogeneic donors. Large volume apheresis (LVL) with a processed volume of more than 4-fold of the patient's blood volume can be used to increase the CD34+ yield in patients with low CD34+ pre-counts, resulting in higher yields of CD34+ cells for transplantation. Processing of more blood in LVL is achieved by an increase of the blood flow rate and an altered anticoagulation regimen with the occurrence of more citrate reactions.

  2. Stem cells in kidney diseases.

    PubMed

    Soler, María José; José Tomas, Ortiz-Pérez

    2012-01-01

    Circulating bone marrow-derived endothelial progenitor cells (EPCs) seem to play a crucial role in both vasculogenesis and vascular homeostasis. Chronic kidney disease is a state of endothelial dysfunction, accelerated progression of atherosclerosis and high cardiovascular risk. As a consequence, cardiovascular disorders are the main cause of death in end-stage renal disease (ESRD). It has been shown that patients with advanced renal failure have decreased number of bone marrow-derived endothelial progenitor cells and impaired EPCs function. Moreover, in kidney transplant patients, renal graft function significantly correlated with EPC number. The reduced number of EPCs in patients with ESRD has been ascribed to the uremia. Therefore, therapies that improve the uremic status in dialysis patients such as nocturnal hemodialysis are associated with restoration of impaired EPCs number and migratory function. In fact, some of the common treatments for patients with chronic kidney disease such as erythropoietin, statins and angiotensin II receptor antagonist increase the number of EPCs. Nowadays, there is growing evidence indicating that, under pathophysiological conditions, stem cells (SCs) derived from bone marrow are able to migrate in the injured kidney, and they seem to play a role in glomerular and tubular regeneration. After acute tubular renal injury, surviving tubular epithelial cells and putative renal stem cells proliferate and differentiate into tubular epithelial cells to promote structural and functional repair. Moreover, bone marrow stem cells, including hematopoietic stem cells and mesenchymal stem cells can also participate in the repair process by proliferation and differentiation into renal lineages. For instance, mesenchymal SCs have been shown to decrease inflammation and enhance renal regeneration. The administration of ex vivo expanded bone marrow-derived mesenchymal SCs have been proved to be beneficial in various experimental models of acute

  3. Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

    PubMed

    Duelen, Robin; Sampaolesi, Maurilio

    2017-01-27

    Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation.

  4. An introduction to stem cell biology.

    PubMed

    Hemmat, Shirin; Lieberman, David M; Most, Sam P

    2010-10-01

    The field of stem cell biology has undergone tremendous expansion over the past two decades. Scientific investigation has continued to expand our understanding of these complex cells at a rapidly increasing rate. This understanding has produced a vast array of potential clinical applications. This article will serve as an overview of the current state of stem cell research as it applies to scientific and medical applications. Included in the discussion is a review of the many different types of stem cells, including but not limited to adult, embryonic, and perinatal stem cells. Also, this article describes somatic cell nuclear transfer, an exciting technology that allows the production of totipotent stem cells from fully differentiated cells, thereby eliminating the use of embryonic sources. This discussion should serve as a review of the field of stem cell biology and provide a foundation for the reader to better understand the interface of stem cell technology and facial plastic and reconstructive surgery.

  5. Stem/Progenitor cells in vascular regeneration.

    PubMed

    Zhang, Li; Xu, Qingbo

    2014-06-01

    A series of studies has been presented in the search for proof of circulating and resident vascular progenitor cells, which can differentiate into endothelial and smooth muscle cells and pericytes in animal and human studies. In terms of pluripotent stem cells, including embryonic stem cells, iPS, and partial-iPS cells, they display a great potential for vascular lineage differentiation. Development of stem cell therapy for treatment of vascular and ischemic diseases remains a major challenging research field. At the present, there is a clear expansion of research into mechanisms of stem cell differentiation into vascular lineages that are tested in animal models. Although there are several clinical trials ongoing that primarily focus on determining the benefits of stem cell transplantation in ischemic heart or peripheral ischemic tissues, intensive investigation for translational aspects of stem cell therapy would be needed. It is a hope that stem cell therapy for vascular diseases could be developed for clinic application in the future.

  6. Epidermal stem cells and their epigenetic regulation.

    PubMed

    Shen, Qi; Jin, Hongchuan; Wang, Xian

    2013-08-30

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

  7. Rejuvenating Strategies for Stem Cell-Based Therapies in Aging.

    PubMed

    Neves, Joana; Sousa-Victor, Pedro; Jasper, Heinrich

    2017-02-02

    Recent advances in our understanding of tissue regeneration and the development of efficient approaches to induce and differentiate pluripotent stem cells for cell replacement therapies promise exciting avenues for treating degenerative age-related diseases. However, clinical studies and insights from model organisms have identified major roadblocks that normal aging processes impose on tissue regeneration. These new insights suggest that specific targeting of environmental niche components, including growth factors, ECM, and immune cells, and intrinsic stem cell properties that are affected by aging will be critical for the development of new strategies to improve stem cell function and optimize tissue repair processes.

  8. College Students' Conceptions of Stem Cells, Stem Cell Research, and Cloning

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  9. Stem cells and colorectal carcinogenesis

    PubMed Central

    Stoian, M; Stoica, V; Radulian, G

    2016-01-01

    Abstract Colorectal cancer represents an important cause of mortality and morbidity. Unfortunately, the physiopathology is still under study. There are theories about carcinogenesis and it is known that not only a single factor is responsible for the development of a tumor, but several conditions. Stem cells are a promising target for the treatment of colorectal cancer, along with the environment that has an important role. It has been postulated that mutations within the adult colonic stem cells may induce neoplastic changes. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumor and therefore they are responsible for recurrence. It is important to know that a new way of treatment needs to be found, since these cells are resistant to chemotherapy and radiotherapy. PMID:27713769

  10. [Cell transplant and regenerative stem cell therapy].

    PubMed

    Prosper, F

    2008-01-01

    The derivation of the first human embryonic stem cell lines as well as the notion of the unexpected plasticity and potential of the adult stem cells has significantly impacted the biomedical research. Many of the tissues long believe to lack any regenerative capacity has demonstrated otherwise. Patients alike physicians expectations for treatment of incurable diseases have also fuelled this field and in occasions have led to unrealistic expectations. In the next pages I review some of the tissue specific stem cells that have been used either in preclinical models or even in clinical research. Despite the effort of numerous investigators, more questions that answers remain in the field of cell therapy and only careful and independent -not biased- research will allow us to translate some of this findings into clinical application.

  11. Skin Stem Cells: At the Frontier Between the Laboratory and Clinical Practice. Part 1: Epidermal Stem Cells.

    PubMed

    Pastushenko, I; Prieto-Torres, L; Gilaberte, Y; Blanpain, C

    2015-11-01

    Stem cells are characterized by their ability to self-renew and differentiate into the different cell lineages of their tissue of origin. The discovery of stem cells in adult tissues, together with the description of specific markers for their isolation, has opened up new lines of investigation, expanding the horizons of biomedical research and raising new hope in the treatment of many diseases. In this article, we review in detail the main characteristics of the stem cells that produce the specialized cells of the skin (epidermal, mesenchymal, and melanocyte stem cells) and their potential implications and applications in diseases affecting the skin. Part I deals with the principal characteristics and potential applications of epidermal stem cells in dermatology.

  12. Setting FIRES to Stem Cell Research

    ERIC Educational Resources Information Center

    Miller, Roxanne Grietz

    2005-01-01

    The goal of this lesson is to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. One of the challenges of discussing stem cell research is that the field is constantly evolving and the most current information changes almost daily. Few…

  13. Retinal stem cells and potential cell transplantation treatments.

    PubMed

    Lin, Tai-Chi; Hsu, Chih-Chien; Chien, Ke-Hung; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Chen, Shih-Jen

    2014-11-01

    The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone) and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells). The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  14. Stem Cells for Neurovascular Repair in Stroke

    PubMed Central

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

    2013-01-01

    Stem cells exert therapeutic effects against ischemic stroke via transplantation of exogenous stem cells or stimulation of endogenous stem cells within the neurogenic niches of subventricular zone and subgranular zone, or recruited from the bone marrow through peripheral circulation. In this paper, we review the different sources of stem cells that have been tested in animal models of stroke. In addition, we discuss specific mechanisms of action, in particular neurovascular repair by endothelial progenitor cells, as key translational research for advancing the clinical applications of stem cells for ischemic stroke. PMID:24077523

  15. Somatic stem cell biology and periodontal regeneration.

    PubMed

    Zhu, Bin; Liu, Yihan; Li, Dehua; Jin, Yan

    2013-01-01

    Somatic stem cells have been acknowledged for their ability to differentiate into multiple cell types and their capacity for self-renewal. Some mesenchymal stem cells play a dominant role in the repair and reconstruction of periodontal tissues. Both dental-derived and some non-dental-derived mesenchymal stem cells possess the capacity for periodontal regeneration under certain conditions with induced differentiation, proliferation, cellular secretion, and their interactions. Stem cell-based tissue engineering technology promises to bring improvements to periodontal regeneration, biologic tooth repair, and bioengineered implants. The present review discusses the roles and values of various somatic stem cells in periodontal regeneration.

  16. Cancer Stem Cells in Lung Tumorigenesis

    PubMed Central

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2011-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continued research in the field of lung cancer stem cell biology is vital, as ongoing efforts promise to yield new prognostic and therapeutic targets. PMID:20493987

  17. Notch signaling in cancer stem cells.

    PubMed

    Wang, Jialiang; Sullenger, Bruce A; Rich, Jeremy N

    2012-01-01

    Subpopulations of cancer cells with stem cell-like characteristics, termed cancer stem cells, have been identified in a wide range of human cancers. Cancer stem cells are defined by their ability to self-renew as well as recapitulate the original heterogeneity of cancer cells in culture and in serial xenotransplants. Not only are cancer stem cells highly tumorigenic, but these cells are implicated in tumor resistance to conventional chemotherapy and radiotherapy, thus highlighting their significance as therapeutic targets. Considerable similarities have been found between cancer stem cells and normal stem cells on their dependence on certain signaling pathways. More specifically, the core stem cell signaling pathways, such as the Wnt, Notch and Hedgehog pathways, also critically regulate the self-renewal and survival of cancer stem cells. While the oncogenic functions of Notch pathway have been well documented, its role in cancer stem cells is just emerging. In this chapter, we will discuss recent advances in cancer stem cell research and highlight the therapeutic potential of targeting Notch in cancer stem cells.

  18. Methods for Stem Cell Production and Therapy

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

  19. Nuclear Mechanics and Stem Cell Differentiation.

    PubMed

    Mao, Xinjian; Gavara, Nuria; Song, Guanbin

    2015-12-01

    Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

  20. Stem Cells in Prostate

    DTIC Science & Technology

    2005-03-01

    disease upon aging, specifically prostate cancer and benign prostatic hyperplasia . In order to study the cell differentiation lineage associated with...specifically prostate cancer and benign prostatic hyperplasia . In order to study the cell differentiation lineage associated with normal and diseased prostate

  1. Endometrial stem cells in regenerative medicine.

    PubMed

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

    2014-01-01

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

  2. Stem cells: are we ready for therapy?

    PubMed

    Schroeder, Insa S

    2014-01-01

    Cell therapy as a replacement for diseased or destroyed endogenous cells is a major component of regenerative medicine. Various types of stem cells are or will be used in clinical settings as autologous or allogeneic products. In this chapter, the progress that has been made to translate basic stem cell research into pharmaceutical manufacturing processes will be reviewed. Even if in public perception, embryonic stem (ES) cells and more recently induced pluripotent stem (iPS) cells dominate the field of regenerative medicine and will be discussed in great detail, it is the adult stem cells that are used for decades as therapeutics. Hence, these cells will be compared to ES and iPS cells. Finally, special emphasis will be placed on the scientific, technical, and economic challenges of developing stem cell-based in vitro model systems and cell therapies that can be commercialized.

  3. Challenges for heart disease stem cell therapy

    PubMed Central

    Hoover-Plow, Jane; Gong, Yanqing

    2012-01-01

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

  4. Embryonic stem cell patents and human dignity.

    PubMed

    Resnik, David B

    2007-09-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells.

  5. Embryonic Stem Cell Patents and Human Dignity

    PubMed Central

    Resnik, David B.

    2009-01-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. PMID:17922198

  6. Stem cell maintenance in a different niche

    PubMed Central

    Ahn, Ji Yeon; Lee, Seung Tae

    2013-01-01

    To overcome the difficulty of controlling stem cell fate and function in applications to regenerative medicine, a number of alternative approaches have been made. Recent reports demonstrate that a non-cellular niche modulating the biophysical microenvironment with chemical factors can support stem cell self-renewal. In our previous studies, early establishment was executed to optimize biophysical factors and it was subsequently found that the microgeometry of the extracellular matrix made huge differences in stem cell behavior and phenotype. We review here a three-dimensional, non-cellular niche designed to support stem cell self-renewal. The characteristics of stem cells under the designed system are further discussed. PMID:23875159

  7. Mesenchymal stem cell exosomes.

    PubMed

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Lim, Sai Kiang

    2015-04-01

    MSCs are an extensively used cell type in clinical trials today. The initial rationale for their clinical testing was based on their differentiation potential. However, the lack of correlation between functional improvement and cell engraftment or differentiation at the site of injury has led to the proposal that MSCs exert their effects not through their differentiation potential but through their secreted product, more specifically, exosomes, a type of extracellular vesicle. We propose here that MSC exosomes function as an extension of MSC's biological role as tissue stromal support cells. Like their cell source, MSC exosomes help maintain tissue homeostasis for optimal tissue function. They target housekeeping biological processes that operate ubiquitously in all tissues and are critical in maintaining tissue homeostasis, enabling cells to recover critical cellular functions and begin repair and regeneration. This hypothesis provides a rationale for the therapeutic efficacy of MSCs and their secreted exosomes in a wide spectrum of diseases. Here, we give a brief introduction of the biogenesis of MSC exosomes, review their physiological functions and highlight some of their biochemical potential to illustrate how MSC exosomes could restore tissue homeostasis leading to tissue recovery and repair.

  8. Klotho, stem cells, and aging

    PubMed Central

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders. PMID:26346243

  9. Klotho, stem cells, and aging.

    PubMed

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.

  10. Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.

    PubMed

    Widmann, Thomas; Kneer, Harald; König, Jochem; Herrmann, Markus; Pfreundschuh, Michael

    2008-01-01

    Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells after triple stem cell transplantation with prolonged stem cell replication during the first year after stem cell transplantation.

  11. Plasticity of hematopoietic stem cells.

    PubMed

    Ogawa, Makio; LaRue, Amanda C; Mehrotra, Meenal

    2015-01-01

    Almost two decades ago, a number of cell culture and preclinical transplantation studies suggested the striking concept of the tissue-reconstituting ability of hematopoietic stem cells (HSCs). While this heralded an exciting time of radically new therapies for disorders of many organs and tissues, the concept was soon mired by controversy and remained dormant. This chapter provides a brief review of evidence for HSC plasticity including our findings based on single HSC transplantation in mouse. These studies strongly support the concept that HSCs are pluripotent and may be the source for the majority, if not all, of the cell types in our body.

  12. Clinical trials for stem cell therapies

    PubMed Central

    2011-01-01

    In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun. PMID:21569277

  13. Stem Cells News Update: A Personal Perspective

    PubMed Central

    Wong, SC

    2013-01-01

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

  14. Stem cells news update: a personal perspective.

    PubMed

    Wong, Sc

    2013-12-01

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

  15. [Stem cells and tissue engineering techniques].

    PubMed

    Sica, Gigliola

    2013-01-01

    The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

  16. [Ethical aspects of embryonic stem cell research].

    PubMed

    Kostka, U

    2002-11-01

    Research using embryonic stem cells raises a variety of ethical questions, which will be explored in this article. At the core of the ethical controversy is the question of the status of the embryo and its availability for research. A range of countries have approved the use of "supernumerous" embryos from in-vitro fertilization. But ethical problems also arise in reproduction medicine, the informed consent of affected couples, and the targeted production of embryos and egg cell donation for research. The author discuss some of these neglected issues and develops suggestions for comprehensive ethical reflection.

  17. Stem Cells, Science, and Public Reasoning

    ERIC Educational Resources Information Center

    Hurlbut, J. Benjamin; Robert, Jason Scott

    2012-01-01

    These are interesting days in the scientific, social, and political debates about human embryonic stem cell research. Pluripotent stem cells--cells that can, in principle, give rise to the body's full range of cell types--were previously derivable only from human embryos that were destroyed in the process. Now, a variety of somatic cell types can…

  18. Stem cells, mitochondria and aging.

    PubMed

    Ahlqvist, Kati J; Suomalainen, Anu; Hämäläinen, Riikka H

    2015-11-01

    Decline in metabolism and regenerative potential of tissues are common characteristics of aging. Regeneration is maintained by somatic stem cells (SSCs), which require tightly controlled energy metabolism and genomic integrity for their homeostasis. Recent data indicate that mitochondrial dysfunction may compromise this homeostasis, and thereby contribute to tissue degeneration and aging. Progeroid Mutator mouse, accumulating random mtDNA point mutations in their SSCs, showed disturbed SSC homeostasis, emphasizing the importance of mtDNA integrity for stem cells. The mechanism involved changes in cellular redox-environment, including subtle increase in reactive oxygen species (H₂O₂and superoxide anion), which did not cause oxidative damage, but disrupted SSC function. Mitochondrial metabolism appears therefore to be an important regulator of SSC fate determination, and defects in it in SSCs may underlie premature aging. Here we review the current knowledge of mitochondrial contribution to SSC dysfunction and aging. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.

  19. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

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

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  20. Effects of nanotopography on stem cell phenotypes

    PubMed Central

    Ravichandran, Rajeswari; Liao, Susan; Ng, Clarisse CH; Chan, Casey K; Raghunath, Michael; Ramakrishna, Seeram

    2009-01-01

    Stem cells are unspecialized cells that can self renew indefinitely and differentiate into several somatic cells given the correct environmental cues. In the stem cell niche, stem cell-extracellular matrix (ECM) interactions are crucial for different cellular functions, such as adhesion, proliferation, and differentiation. Recently, in addition to chemical surface modifications, the importance of nanometric scale surface topography and roughness of biomaterials has increasingly becoming recognized as a crucial factor for cell survival and host tissue acceptance in synthetic ECMs. This review describes the influence of nanotopography on stem cell phenotypes. PMID:21607108

  1. Stem cell directed gene therapy.

    PubMed

    Engel, B C; Kohn, D B

    1999-05-01

    A potential therapeutic approach to HIV-1 infection is the genetic modification of cells of a patient to make them resistant to HIV-1. Hematopoietic stem cells are an attractive target for gene therapy of AIDS because of their ability to generate a broad repertoire of mature T lymphocytes, as well as the monocytic cells (macrophages, dendritic cells and microglia) which are also involved in HIV-1 pathogenesis. A number of synthetic "anti-HIV-1 genes" have been developed which inhibit HIV-1 replication. However, current methods for gene transfer into human hematopoietic stem cells, using retroviral vectors derived from the Moloney murine leukemia virus, have been minimally effective. Clinical trials performed to date in which hematopoietic cells from HIV-1-positive patients have been transduced with retroviral vectors and then reinfused have produced low to undetectable levels of gene-containing peripheral blood leukocytes. New vector delivery systems, such as lentiviral vectors, need to be developed to ensure efficient gene transfer and persistent transgene expression to provide life-long resistance to the cells targeted by HIV-1.

  2. Cancer stem cells and metastasis.

    PubMed

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

    Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

  3. Embryonic stem cells: testing the germ-cell theory.

    PubMed

    Hochedlinger, Konrad

    2011-10-25

    The exact cellular origin of embryonic stem cells remains elusive. Now a new study provides compelling evidence that embryonic stem cells, established under conventional culture conditions, originate from a transient germ-cell state.

  4. Haematopoietic stem cells: past, present and future

    PubMed Central

    Ng, Ashley P; Alexander, Warren S

    2017-01-01

    The discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as a source of haematopoietic cells capable of protecting an organism from otherwise lethal irradiation led to the intense search for their identity and characteristics. Using functional assays along with evolving techniques for isolation of haematopoietic cells, haematopoietic stem cell populations were able to be enriched and their characteristics analysed. The key haematopoietic stem cell characteristics of pluripotentiality and the ability for self-renewal have emerged as characteristics of several haematopoietic stem cell populations, including those that have recently challenged the conventional concepts of the haematopoietic hierarchy. Human allogeneic stem cell therapy relies on these functional characteristics of haematopoietic stem cells that can be isolated from peripheral blood, bone marrow or cord blood, with the additional requirement that immunological barriers need to be overcome to allow sustained engraftment while minimising risk of graft-versus-host disease developing in the recipient of transplanted stem cells. Current and future research will continue to focus on the identification of haematopoietic stem cell regulators and methods for in vitro and in vivo stem cell manipulation, including genome editing, to expand the scope, potential and safety of therapy using haematopoietic stem cells. PMID:28180000

  5. Making new beta cells from stem cells.

    PubMed

    Colman, Alan

    2004-06-01

    In 2000, Shapiro et al. provided compelling "proof of principle" data showing that the transplantation of human islets, purified from cadaveric material, could restore severely diabetic, Type 1 patients to insulin independence. This demonstration prompted renewed efforts to find an alternative and sustainable source of surrogate islet cells for cell therapy. Experiments involving adult ductal and liver "stem" cells, or embryonic stem cells, are prominent amongst these endeavors and are reviewed in this article. Whilst there are many published claims to success in converting ES cells into insulin secreting, glucose responsive cells, all require careful reinterpretation in the light of findings that cells can adsorb insulin present in growth media. It is likely that work with adult cells is less prone to this potential artifact and significant progress has been made in producing insulin-secreting cells. Assessment of in vivo function in the surrogate cells is most frequently made using cell transplantation into toxin-induced, diabetic mice, but this model is rarely used to maximal advantage. In many cases, it remains unclear whether reductions in the hyperglycemia result from insulin secretion from the transplanted cells or are due to recovery of endogenous islet function. In this latter context, experiments are reviewed where endogenous stimulation of recovery is engendered even by irradiated donor cells.

  6. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging.

    PubMed

    Marycz, Krzysztof; Kornicka, Katarzyna; Basinska, Katarzyna; Czyrek, Aleksandra

    2016-01-01

    Currently, equine metabolic syndrome (EMS), an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC). Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN) and horses suffering from EMS (ASCEMS). ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO) and reactive oxygen species (ROS) in these cells, accompanied by reduced superoxide dismutase (SOD) activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS.

  7. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging

    PubMed Central

    Marycz, Krzysztof; Kornicka, Katarzyna; Basinska, Katarzyna; Czyrek, Aleksandra

    2016-01-01

    Currently, equine metabolic syndrome (EMS), an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC). Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN) and horses suffering from EMS (ASCEMS). ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO) and reactive oxygen species (ROS) in these cells, accompanied by reduced superoxide dismutase (SOD) activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS. PMID:26682006

  8. Anti-Cancer Phytometabolites Targeting Cancer Stem Cells.

    PubMed

    Torquato, Heron F V; Goettert, Márcia I; Justo, Giselle Z; Paredes-Gamero, Edgar J

    2017-04-01

    Medicinal plants are a plentiful source of bioactive molecules with much structural diversity. In cancer treatment, molecules obtained from plants represent an attractive alternative to other treatments because several plant-derived compounds have exhibited lower toxicity and higher selectivity against cancer cells. In this review, we focus on the possible application of bioactive molecules obtained from plants against more primitive cell populations in cancers, cancer stem cells. Cancer stem cells are present in several kinds of tumors and are responsible for recurrences and metastases. Common anti-cancer drugs exhibit lower effectiveness against cancer stem cells because of their biological features. However, recently discovered natural phytometabolites exert cytotoxic effects on this rare population of cells in cancers. Therefore, this review presents the latest research on promising compounds from plants that can act as antitumor drugs and that mainly affect stem cell populations in cancers.

  9. Metronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells.

    PubMed

    Vives, Marta; Ginestà, Mireia M; Gracova, Kristina; Graupera, Mariona; Casanovas, Oriol; Capellà, Gabriel; Serrano, Teresa; Laquente, Berta; Viñals, Francesc

    2013-11-15

    In this article, the effectiveness of a multi-targeted chemo-switch (C-S) schedule that combines metronomic chemotherapy (MET) after treatment with the maximum tolerated dose (MTD) is reported. This schedule was tested with gemcitabine in two distinct human pancreatic adenocarcinoma orthotopic models and with cyclophosphamide in an orthotopic ovarian cancer model. In both models, the C-S schedule had the most favourable effect, achieving at least 80% tumour growth inhibition without increased toxicity. Moreover, in the pancreatic cancer model, although peritoneal metastases were observed in control and MTD groups, no dissemination was observed in the MET and C-S groups. C-S treatment caused a decrease in angiogenesis, and its effect on tumour growth was similar to that produced by the MTD followed by anti-angiogenic DC101 treatment. C-S treatment combined an increase in thrombospondin-1 expression with a decrease in the number of CD133+ cancer cells and triple-positive CD133+/CD44+/CD24+ cancer stem cells (CSCs). These findings confirm that the C-S schedule is a challenging clinical strategy with demonstrable inhibitory effects on tumour dissemination, angiogenesis and CSCs.

  10. Breast Cancer Stem Cells in Antiestrogen Resistance

    DTIC Science & Technology

    2013-08-01

    stimulated by antiestrogens. The effects of antiestrogens on the ER-positive breast cancer stem/progenitor involve changes of both proliferation and...self-renewal capabilities of breast cancer stem/progenitor cells. The effects of antiestrogens on the ER- positive breast cancer stem/progenitor...potent tumor-seeding efficiency. . Fig 3. The effects of antiestrogens on the differentiation of ER-positive breast cancer stem cells expressing

  11. Stem Cells in the Nervous System

    PubMed Central

    Maldonado-Soto, Angel R.; Oakley, Derek H.; Wichterle, Hynek; Stein, Joel; Doetsch, Fiona K.; Henderson, Christopher E.

    2014-01-01

    Given their capacity to regenerate cells lost through injury or disease, stem cells offer new vistas into possible treatments for degenerative diseases and their underlying causes. As such, stem cell biology is emerging as a driving force behind many studies in the field of regenerative medicine. This review focuses on our current understanding of the applications of stem cells in treating ailments of the human brain, with an emphasis on neurodegenerative diseases. Two types of neural stem cells are discussed: endogenous neural stem cells residing within the adult brain, and pluripotent stem cells capable of forming neural cells in culture. Endogenous neural stem cells give rise to neurons throughout life, but they are restricted to specialized regions in the brain. Elucidating the molecular mechanisms regulating these cells is key in determining their therapeutic potential, as well as finding mechanisms to activate dormant stem cells outside of these specialized microdomains. In parallel, patient-derived stem cells can be used to generate neural cells in culture, providing new tools for disease modeling, drug testing and cell-based therapies. Turning these technologies into viable treatments will require the integration of basic science with clinical skills in rehabilitation. PMID:24800720

  12. Engineering Stem Cells for Biomedical Applications.

    PubMed

    Yin, Perry T; Han, Edward; Lee, Ki-Bum

    2016-01-07

    Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer.

  13. Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes?

    PubMed

    Kahraman, Sevim; Okawa, Erin R; Kulkarni, Rohit N

    2016-08-01

    Diabetes is a progressive disease affecting millions of people worldwide. There are several medications and treatment options to improve the life quality of people with diabetes. One of the strategies for the treatment of diabetes could be the use of human pluripotent stem cells or induced pluripotent stem cells. The recent advances in differentiation of stem cells into insulin-secreting beta-like cells in vitro make the transplantation of the stem cell-derived beta-like cells an attractive approach for treatment of type 1 and type 2 diabetes. While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases.

  14. Reforming craniofacial orthodontics via stem cells.

    PubMed

    Mohanty, Pritam; Prasad, N K K; Sahoo, Nivedita; Kumar, Gunjan; Mohanty, Debapreeti; Sah, Sushila

    2015-01-01

    Stem cells are the most interesting cells in cell biology. They have the potential to evolve as one of the most powerful technologies in the future. The future refers to an age where it will be used extensively in various fields of medical and dental sciences. Researchers have discovered a number of sources from which stem cells can be derived. Craniofacial problems are very common and occur at all ages. Stem cells can be used therapeutically in almost every field of health science. In fact, many procedures will be reformed after stem cells come into play. This article is an insight into the review of the current researches being carried out on stem cells and its use in the field of orthodontics, which is a specialized branch of dentistry. Although the future is uncertain, there is a great possibility that stem cells will be used extensively in almost all major procedures of orthodontics.

  15. Lung stem cell update: promise and controversy.

    PubMed

    Neuringer, I P; Randell, S H

    2006-03-01

    Currently, there is great enthusiasm about potential stem cell therapies for intractable diseases. We previously reviewed the topic of stem cells in lung injury and repair, including the role of endogenous, tissue (somatic) stem cells and the contribution of circulating cells to the lung parenchyma. Our purpose here is to provide a concise update in this fast-moving field. New information and ongoing debate focus attention on basic issues in lung stem cell biology and highlight the need for additional studies to establish the feasibility of cell therapies to prevent or treat lung diseases.

  16. Stem Cells for Augmenting Tendon Repair

    PubMed Central

    Gulotta, Lawrence V.; Chaudhury, Salma; Wiznia, Daniel

    2012-01-01

    Tendon healing is fraught with complications such as reruptures and adhesion formation due to the formation of scar tissue at the injury site as opposed to the regeneration of native tissue. Stem cells are an attractive option in developing cell-based therapies to improve tendon healing. However, several questions remain to be answered before stem cells can be used clinically. Specifically, the type of stem cell, the amount of cells, and the proper combination of growth factors or mechanical stimuli to induce differentiation all remain to be seen. This paper outlines the current literature on the use of stem cells for tendon augmentation. PMID:22190960

  17. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    SciTech Connect

    Varga, Nora; Vereb, Zoltan; Rajnavoelgyi, Eva; Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs; Apati, Agota

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  18. Stem Cells in the Cornea

    PubMed Central

    Hertsenberg, Andrew J.; Funderburgh, James L.

    2017-01-01

    The cornea is the tough, transparent tissue through which light first enters the eye and functions as a barrier to debris and infection as well as two-thirds of the refractive power of the eye. Corneal damage that is not promptly treated will often lead to scarring and vision impairment. Due to the limited options currently available to treat corneal scars, the identification and isolation of stem cells in the cornea has received much attention, as they may have potential for autologous, cell-based approaches to the treatment of damaged corneal tissue. PMID:26310147

  19. Concise Review: Stem Cell Therapies for Neuropathic Pain

    PubMed Central

    Fortino, Veronica R.; Pelaez, Daniel

    2013-01-01

    Neuropathic pain is a chronic condition that is heterogeneous in nature and has different causes. Different from and more burdensome than nociceptive pain, neuropathic pain more severely affects people's quality of life. Understanding the various mechanisms of the onset and progression of neuropathic pain is important in the development of an effective treatment. Research is being done to replace current pharmacological treatments with cellular therapies that will have longer lasting effects. Stem cells present an exciting potential therapy for neuropathic pain. In this review, we describe the neuroprotective effects of stem cells along with special emphasis on the current translational research using stem cells to treat neuropathic pain. PMID:23572051

  20. What Is a Blood and Marrow Stem Cell Transplant?

    MedlinePlus

    ... and Bone Marrow Transplant Also known as hematopoietic stem cell transplant, hematopoietic cell transplant, autologous transplant, or allogeneic ... or bone marrow transplant replaces abnormal blood-forming stem cells with healthy cells. When the healthy stem cells ...

  1. PEDF & stem cells: niche vs. nurture.

    PubMed

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

    2014-01-01

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

  2. Mesenchymal dental stem cells in regenerative dentistry.

    PubMed

    Rodríguez-Lozano, Francisco-Javier; Insausti, Carmen-Luisa; Iniesta, Francisca; Blanquer, Miguel; Ramírez, María-del-Carmen; Meseguer, Luis; Meseguer-Henarejos, Ana-Belén; Marín, Noemí; Martínez, Salvador; Moraleda, José-María

    2012-11-01

    In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in the known of growth factors and signalling molecules implicated in tooth development and regeneration of different structures of teeth. Furthermore, these cells need a fabulous scaffold that facility their integration, differentiation, matrix synthesis and promote multiple specific interactions between cells. In this review, we give a brief description of tooth development and anatomy, definition and classification of stem cells, with special attention of mesenchymal stem cells, commonly used in the cellular therapy for their trasdifferentiation ability, non ethical problems and acceptable results in preliminary clinical trials. In terms of tissue engineering, we provide an overview of different types of mesenchymal stem cells that have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs), growth factors implicated in regeneration teeth and types of scaffolds for dental tissue regeneration.

  3. Infection, stem cells and cancer signals.

    PubMed

    Sell, S

    2011-02-01

    The association of cancer with preceding parasitic infections has been observed for over 200 years. Some such cancers arise from infection of tissue stem cells by viruses with insertion of viral oncogenes into the host DNA (mouse polyoma virus, mouse mammary tumor virus). In other cases the virus does not insert its DNA into the host cells, but rather commandeers the metabolism of the infected cells, so that the cells continue to proliferate and do not differentiate (human papilloma virus and cervical cancer). Cytoplasmic Epstein Barr virus infection is associated with a specific gene translocation (Ig/c-myc) that activates proliferation of affected cells (Burkitt lymphoma). In chronic osteomyelitis an inflammatory reaction to the infection appears to act through production of inflammatory cytokines and oxygen radical formation to induce epithelial cancers. Infection with Helicobacter pylori leads to epigenetic changes in methylation and infection by a parasite. Clonorchis sinensis also acts as a promoter of cancer of the bile ducts of the liver (cholaniocarcinoma). The common thread among these diverse pathways is that the infections act to alter tissue stem cell signaling with continued proliferation of tumor transit amplifying cells.

  4. Infection, Stem Cells and Cancer Signals

    PubMed Central

    Sell, S.

    2013-01-01

    The association of cancer with preceding parasitic infections has been observed for over 200 years. Some such cancers arise from infection of tissue stem cells by viruses with insertion of viral oncogenes into the host DNA (mouse polyoma virus, mouse mammary tumor virus). In other cases the virus does not insert its DNA into the host cells, but rather commandeers the metabolism of the infected cells, so that the cells continue to proliferate and do not differentiate (human papilloma virus and cervical cancer). Cytoplasmic Epstein Barr virus infection is associated with a specific gene translocation (Ig/c-myc) that activates proliferation of affected cells (Burkitt lymphoma). In chronic osteomyelitis an inflammatory reaction to the infection appears to act through production of inflammatory cytokines and oxygen radical formation to induce epithelial cancers. Infection with Helicobacter pylori leads to epigenetic changes in methylation and infection by a parasite. Clonorchis sinensis also acts as a promoter of cancer of the bile ducts of the liver (cholaniocarcinoma). The common thread among these diverse pathways is that the infections act to alter tissue stem cell signaling with continued proliferation of tumor transit amplifying cells. PMID:21044009

  5. Induced Pluripotent Stem Cells: Characteristics and Perspectives

    NASA Astrophysics Data System (ADS)

    Cantz, Tobias; Martin, Ulrich

    The induction of pluripotency in somatic cells is widely considered as a major breakthrough in regenerative medicine, because this approach provides the basis for individualized stem cell-based therapies. Moreover, with respect to cell transplantation and tissue engineering, expertise from bioengineering to transplantation medicine is now meeting basic research of stem cell biology.

  6. TGF-β1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG2 cells.

    PubMed

    Wang, Xin-Hong; Liu, Ming-Na; Sun, Xun; Xu, Chun-Huan; Liu, Jing; Chen, Jing; Xu, Rui-Ling; Li, Bao-Xin

    2016-03-01

    Liver cancer is one of the most common human malignancies, and transforming growth factor-beta (TGF-β) pathway plays a key role in its pathogenesis. To study the relationship between TGF-β pathway and the related protein expression of many signaling pathway, markers of stem cells, CK family, and others, liver cancer HepG2 cells were transfected with siRNA directed against TGF-β1 or were treated with exogenous TGF-β1. Then, these protein levels were measured by Western blotting. After siRNA transfection, TGF-β1 protein level was decreased, indicating that the siRNA against it was effective. In exogenous TGF-β1 group, the expression of smad4, smad2/3, and β-catenin proteins was increased, whereas that of p-smad2/3, CD133, cleaved Notch1, and epithelial cell adhesion molecule (EpCAM) proteins at 48 h was decreased. The expression of CK8 and CK18 proteins was increased at 24 h and was decreased at 48 and 96 h. In TGF-β1-silenced group, the expression of smad2/3, β-catenin, cleaved-notch1, and CK18 proteins was decreased, while that of smad4, p-smad2/3, CD133, EpCAM, and CK8 proteins was increased. TERT protein expression was slightly increased in exogenous TGF-β1 group at 48 h and in TGF-β1-silenced group at 96 h. TGF-β1 did not affect the protein expression of CK19 and HIF-1. Thus, TGF-β1 pathway plays an important role in cell regulation of liver cancer through the modulation of these proteins. These data will contribute to the understanding of the pathogenesis of liver cancer and the role of TGF-β pathway in this process.

  7. Proliferation control in neural stem and progenitor cells

    PubMed Central

    Homem, Catarina CF; Repic, Marko; Knoblich, Juergen A

    2015-01-01

    Neural circuit function can be drastically affected by variations in the number of cells that are produced during development or by a reduction in adult cell number due to disease. Unlike many other organs, the brain is unable to compensate for such changes by increasing cell numbers or altering the size of the cells. For this reason, unique cell cycle and cell growth control mechanisms operate in the developing and adult brain. In Drosophila melanogaster and mammalian neural stem and progenitor cells these mechanisms are intricately coordinated with the developmental age and the nutritional, metabolic and hormonal state of the animal. Defects in neural stem cell proliferation that result in the generation of incorrect cell numbers or defects in neural stem cell differentiation can cause microcephaly or megalencephaly. PMID:26420377

  8. All hematopoietic stem cells engraft in submyeloablatively irradiated mice.

    PubMed

    Forgacova, Katarina; Savvulidi, Filipp; Sefc, Ludek; Linhartova, Jana; Necas, Emanuel

    2013-05-01

    Significant controversy exists regarding the impact of hematopoietic stroma damage by irradiation on the efficiency of engraftment of intravenously transplanted stem cells. It was previously demonstrated that in normal syngenic mice, all intravenously transplanted donor stem cells, present in the bone marrow, compete equally with those of the host. In this study, we comprehensively compared the blood cell production derived from transplanted donor stem cells with that from the host stem cells surviving various doses of submyeloablative irradiation. We compared the partial chimerism resulting from transplantation with theoretical estimates that assumed transplantation efficiencies ranging from 100% to 20%. The highest level of consensus between the experimental and the theoretical results was 100% for homing and engraftment (ie, the utilization of all transplanted stem cells). These results point to a very potent mechanism through which intravenously administered hematopoietic stem cells are captured from circulation, engraft in the hematopoietic tissue, and contribute to blood cell production in irradiated recipients. The damage done to hematopoietic stroma and to the trabecular bone by submyeloablative doses of ionizing radiation does not negatively affect the homing and engraftment mechanisms of intravenously transplanted hematopoietic progenitor and stem cells.

  9. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    DTIC Science & Technology

    2015-07-01

    stem cells (CSCs)- stem cell like cells in tumors that have stem cell properties and tumor initiating ability- retain epigenetic memories of their...months showing megacephaly. Abb: ctx=cortex, cb= cerebellum, hp= hippocampus Page 5 of 12 To circumvent early lethality associated with PIK3CA

  10. ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells

    PubMed Central

    Riso, Vincenzo; Cammisa, Marco; Kukreja, Harpreet; Anvar, Zahra; Verde, Gaetano; Sparago, Angela; Acurzio, Basilia; Lad, Shraddha; Lonardo, Enza; Sankar, Aditya; Helin, Kristian; Feil, Robert; Fico, Annalisa; Angelini, Claudia; Grimaldi, Giovanna; Riccio, Andrea

    2016-01-01

    ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required. PMID:27257070

  11. Medaka haploid embryonic stem cells.

    PubMed

    Hong, Yunhan

    2010-01-01

    The appearance of diploidy, the presence of two genomes or chromosome sets, is a fundamental hallmark of eukaryotic evolution and bisexual reproduction, because diploidy offers the basis for the bisexual life cycle, allowing for oscillation between diploid and haploid phases. Meiosis produces haploid gametes. At fertilization, male and female gametes fuse to restore diploidy in a zygote, which develops into a new life. At sex maturation, diploid cells enter into meiosis, culminating in the production of haploid gametes. Therefore, diploidy ensures pluripotency, cell proliferation, and functions, whereas haploidy is restricted only to the post-meiotic gamete phase of germline development and represents the end point of cell growth. Diploidy is advantageous for evolution. Haploidy is ideal for genetic analyses, because any recessive mutations of essential genes will show a clear phenotype in the absence of a second gene copy. Recently, my laboratory succeeded in the generation of medaka haploid embryonic stem (ES) cells capable of whole animal production. Therefore, haploidy in a vertebrate is able to support stable cell culture and pluripotency. This finding anticipates the possibility to generate haploid ES cells in other vertebrate species such as zebrafish. These medaka haploid ES cells elegantly combine haploidy and pluripotency, offering a unique yeast-like system for in vitro genetic analyses of molecular, cellular, and developmental events in various cell lineages. This chapter is aimed to describe the strategy of haploid ES cell derivation and their characteristics, and illustrate the perspectives of haploid ES cells for infertility treatment, genetic screens, and analyses.

  12. Mammary stem cells have myoepithelial cell properties

    PubMed Central

    Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  13. Establishment of a Mesenchymal Stem Cell Bank

    PubMed Central

    Cooper, Khushnuma; Viswanathan, Chandra

    2011-01-01

    Adult stem cells have generated great amount of interest amongst the scientific community for their potential therapeutic applications for unmet medical needs. We have demonstrated the plasticity of mesenchymal stem cells isolated from the umbilical cord matrix. Their immunological profile makes it even more interesting. We have demonstrated that the umbilical cord is an inexhaustible source of mesenchymal stem cells. Being a very rich source, instead of discarding this tissue, we worked on banking these cells for regenerative medicine application for future use. The present paper gives a detailed account of our experience in the establishment of a mesenchymal stem cell bank at our facility. PMID:21826152

  14. Pancreatic cancer stem cells: fact or fiction?

    PubMed

    Bhagwandin, Vikash J; Shay, Jerry W

    2009-04-01

    The terms cancer-initiating or cancer stem cells have been the subject of great interest in recent years. In this review we will use pancreatic cancer as an overall theme to draw parallels with historical findings to compare to recent reports of stem-like characteristics in pancreatic cancer. We will cover such topics as label-retaining cells (side-population), ABC transporter pumps, telomerase, quiescence, cell surface stem cell markers, and epithelial-mesenchymal transitions. Finally we will integrate the available findings into a pancreatic stem cell model that also includes metastatic disease.

  15. Effect of aging on stem cells

    PubMed Central

    Ahmed, Abu Shufian Ishtiaq; Sheng, Matilda HC; Wasnik, Samiksha; Baylink, David J; Lau, Kin-Hing William

    2017-01-01

    Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of aging-associated disorders, but also in future development of novel effective stem cell-based therapies to treat aging-associated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects. PMID:28261550

  16. Patenting human genes and stem cells.

    PubMed

    Martin-Rendon, Enca; Blake, Derek J

    2007-01-01

    Cell lines and genetically modified single cell organisms have been considered patentable subjects for the last two decades. However, despite the technical patentability of genes and stem cell lines, social and legal controversy concerning their 'ownership' has surrounded stem cell research in recent years. Some granted patents on stem cells with extremely broad claims are casting a shadow over the commercialization of these cells as therapeutics. However, in spite of those early patents, the number of patent applications related to stem cells is growing exponentially. Both embryonic and adult stem cells have the ability to differentiate into several cell lineages in an organism as a result of specific genetic programs that direct their commitment and cell fate. Genes that control the pluripotency of stem cells have been recently identified and the genetic manipulation of these cells is becoming more efficient with the advance of new technologies. This review summarizes some of the recent published patents on pluripotency genes, gene transfer into stem cells and genetic reprogramming and takes the hematopoietic and embryonic stem cell as model systems.

  17. Stem cell transplantation for rheumatic autoimmune diseases

    PubMed Central

    Hügle, Thomas; van Laar, Jacob M

    2008-01-01

    Immunoablative therapy and hematopoietic stem cell transplantation (HSCT) is an intensive treatment modality aimed at 'resetting' the dysregulated immune system of a patient with immunoablative therapy and allow outgrowth of a nonautogressive immune system from reinfused hematopoietic stem cells, either from the patient (autologous HSCT) or a healthy donor (allogeneic HSCT). HSCT has been shown to induce profound alterations of the immune system affecting B and T cells, monocytes, and natural killer and dendritic cells, resulting in elimination of autoantibody-producing plasma cells and in induction of regulatory T cells. Most of the available data have been collected through retrospective cohort analyses of autologous HSCT, case series, and translational studies in patients with refractory autoimmune diseases. Long-term and marked improvements of disease activity have been observed, notably in systemic sclerosis, systemic lupus erythematosus, and juvenile idiopathic arthritis, and treatment-related morbidity and mortality have improved due to better patient selection and modifications of transplant regimens. Treatment-related mortality has decreased to approximately 7%. Prospective, randomised, controlled clinical trials are ongoing or planned in systemic sclerosis, systemic lupus erythematosus, and several nonrheumatological conditions. PMID:18947373

  18. Stem cell niche engineering through droplet microfluidics.

    PubMed

    Allazetta, Simone; Lutolf, Matthias P

    2015-12-01

    Stem cells reside in complex niches in which their behaviour is tightly regulated by various biochemical and biophysical signals. In order to unveil some of the crucial stem cell-niche interactions and expedite the implementation of stem cells in clinical and pharmaceutical applications, in vitro methodologies are being developed to reconstruct key features of stem cell niches. Recently, droplet-based microfluidics has emerged as a promising strategy to build stem cell niche models in a miniaturized and highly precise fashion. This review highlights current advances in using droplet microfluidics in stem cell biology. We also discuss recent efforts in which microgel technology has been interfaced with high-throughput analyses to engender screening paradigms with an unparalleled potential for basic and applied biological studies.

  19. Stem cells in the light of evolution

    PubMed Central

    Chakraborty, Chiranjib; Agoramoorthy, Govindasamy

    2012-01-01

    All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells. PMID:22825600

  20. Of Microenvironments and Mammary Stem Cells

    SciTech Connect

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  1. [Bioethical challenges of stem cell tourism].

    PubMed

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

    2013-08-01

    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.

  2. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche.

    PubMed

    Chang, Chiung-Ying; Pasolli, H Amalia; Giannopoulou, Eugenia G; Guasch, Géraldine; Gronostajski, Richard M; Elemento, Olivier; Fuchs, Elaine

    2013-03-07

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in

  3. NFIB is a governor of epithelial–melanocyte stem cell behaviour in a shared niche

    PubMed Central

    Chang, Chiung-Ying; Pasolli, H. Amalia; Giannopoulou, Eugenia G.; Guasch, Géraldine; Gronostajski, Richard M.; Elemento, Olivier; Fuchs, Elaine

    2013-01-01

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation1–4. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment2,5. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled

  4. Hematopoietic stem cell transplantation for osteopetrosis.

    PubMed

    Steward, Colin G

    2010-02-01

    Osteopetrosis is the generic name for a group of diseases caused by deficient formation or function of osteoclasts, inherited in either autosomal recessive or dominant fashion. Osteopetrosis varies in severity from a disease that may kill infants to an incidental radiological finding in adults. It is increasingly clear that prognosis is governed by which gene is affected, making detailed elucidation of the cause of the disease a critical component of optimal care, including the decision on whether hematopoietic stem cell transplantation is appropriate. This article reviews the characteristics and management of osteopetrosis.

  5. Overexpression of two cambium-abundant Chinese fir (Cunninghamia lanceolata) α-expansin genes ClEXPA1 and ClEXPA2 affect growth and development in transgenic tobacco and increase the amount of cellulose in stem cell walls.

    PubMed

    Wang, Guifeng; Gao, Yan; Wang, Jinjun; Yang, Liwei; Song, Rentao; Li, Xiaorong; Shi, Jisen

    2011-05-01

    Expansins are unique plant cell wall proteins that possess the ability to induce immediately cell wall extension in vitro and cell expansion in vivo. To investigate the biological functions of expansins that are abundant in wood-forming tissues, we cloned two expansin genes from the differentiating xylem of Chinese fir (Cunninghamia lanceolata (Lamb.) Hook). Phylogenetic reconstruction indicated that they belong to α-expansin (EXPA), named ClEXPA1 and ClEXPA2. Expression pattern analysis demonstrated that they are preferentially expressed in the cambium region. Overexpression of ClEXPA1 and ClEXPA2 in tobacco plants yielded pleiotropic phenotypes of plant height, stem diameter, leaf number and seed pod. The height and diameter growth of the 35S(pro) :ClEXPA1 and 35S(pro) :ClEXPA2 transgenic plants were increased drastically, exhibiting an enlargement of pith parenchyma cell size. Isolated cell walls of ClEXPA1 and ClEXPA2 overexpressors contained 30%-50% higher cellulose contents than the wild type, accompanied by a thickening of the cell walls in the xylem region. Both ClEXPA1 and ClEXPA2 are involved in plant growth and development, with a partially functional overlap. Expansins are not only able to induce cell expansion in different tissues/organs in vivo, but they also can act as a potential activator during secondary wall formation by directly or indirectly affecting cellulose metabolism, probably in a cell type-dependent manner.

  6. Stem cells: classifications, controversies, and clinical applications.

    PubMed

    Fortier, Lisa A

    2005-01-01

    The application of stem cells in regenerative and reparative therapies is emerging in surgery. Published information can lead to an over simplified view of stem cells with respect to their definitions, tissues of origin, abilities to differentiate into tissue lineages, and their capacity for functional tissue regeneration. The goals of this review article are to define embryonic and adult stem cells, compare differences between them, and summarize their potential clinical applications.

  7. Programming Retinal Stem Cells into Cone Photoreceptors

    DTIC Science & Technology

    2015-12-01

    to program human stem cells directly into cones. Using RNA -seq, we identified several genes that are upregulated in advance of the earliest...reverse vision loss. 15. SUBJECT TERMS Cone photoreceptor, retina, retinal stem cell, Otx2, Onecut1, Blimp1, RNA -seq., transcription factors, and...1 Keywords: 1. Cone photoreceptor 2. Retina 3. Retinal stem cell 4. Otx2 5. Onecut1 6. Blimp1 7. RNA -seq. 8. Transcription factors 9

  8. Telomeres, stem cells, and hematology

    PubMed Central

    2008-01-01

    Telomeres are highly dynamic structures that adjust the cellular response to stress and growth stimulation based on previous cell divisions. This critical function is accomplished by progressive telomere shortening and DNA damage responses activated by chromosome ends without sufficient telomere repeats. Repair of critically short telomeres by telomerase or recombination is limited in most somatic cells, and apoptosis or cellular senescence is triggered when too many uncapped telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germ line that typically express high levels of telomerase. In somatic cells, the telomere length typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Loss of (stem) cells via telomere attrition provides strong selection for abnormal cells in which malignant progression is facilitated by genome instability resulting from uncapped telomeres. The critical role of telomeres in cell proliferation and aging is illustrated in patients with 50% of normal telomerase levels resulting from a mutation in one of the telomerase genes. Here, the role of telomeres and telomerase in human biology is reviewed from a personal historical perspective. PMID:18263784

  9. Stem cell reprogramming: A 3D boost

    NASA Astrophysics Data System (ADS)

    Abilez, Oscar J.; Wu, Joseph C.

    2016-03-01

    Biophysical factors in an optimized three-dimensional microenvironment enhance the reprogramming efficiency of human somatic cells into pluripotent stem cells when compared to traditional cell-culture substrates.

  10. Ocular stem cells: a status update!

    PubMed Central

    2014-01-01

    Stem cells are unspecialized cells that have been a major focus of the field of regenerative medicine, opening new frontiers and regarded as the future of medicine. The ophthalmology branch of the medical sciences was the first to directly benefit from stem cells for regenerative treatment. The success stories of regenerative medicine in ophthalmology can be attributed to its accessibility, ease of follow-up and the eye being an immune-privileged organ. Cell-based therapies using stem cells from the ciliary body, iris and sclera are still in animal experimental stages but show potential for replacing degenerated photoreceptors. Limbal, corneal and conjunctival stem cells are still limited for use only for surface reconstruction, although they might have potential beyond this. Iris pigment epithelial, ciliary body epithelial and choroidal epithelial stem cells in laboratory studies have shown some promise for retinal or neural tissue replacement. Trabecular meshwork, orbital and sclera stem cells have properties identical to cells of mesenchymal origin but their potential has yet to be experimentally determined and validated. Retinal and retinal pigment epithelium stem cells remain the most sought out stem cells for curing retinal degenerative disorders, although treatments using them have resulted in variable outcomes. The functional aspects of the therapeutic application of lenticular stem cells are not known and need further attention. Recently, embryonic stem cell-derived retinal pigment epithelium has been used for treating patients with Stargardts disease and age-related macular degeneration. Overall, the different stem cells residing in different components of the eye have shown some success in clinical and animal studies in the field of regenerative medicine. PMID:25158127

  11. Plant stem cells as innovation in cosmetics.

    PubMed

    Moruś, Martyna; Baran, Monika; Rost-Roszkowska, Magdalena; Skotnicka-Graca, Urszula

    2014-01-01

    The stem cells thanks to their ability of unlimited division number or transformation into different cell types creating organs, are responsible for regeneration processes. Depending on the organism in which the stem cells exists, they divide to the plant or animal ones. The later group includes the stem cells existing in both embryo's and adult human's organs. It includes, among others, epidermal stem cells, located in the hair follicle relieves and also in its basal layers, and responsible for permanent regeneration of the epidermis. Temporary science looks for method suitable for stimulation of the epidermis stem cells, amongst the other by delivery of e.g., growth factors for proliferation that decrease with the age. One of the methods is the use of the plant cell culture technology, including a number of methods that should ensure growth of plant cells, issues or organs in the environment with the microorganism-free medium. It uses abilities of the different plant cells to dedifferentiation into stem cells and coming back to the pluripotent status. The extracts obtained this way from the plant stem cells are currently used for production of both common or professional care cosmetics. This work describes exactly impact of the plant stem cell extract, coming from one type of the common apple tree (Uttwiler Spätlauber) to human skin as one of the first plant sorts, which are used in cosmetology and esthetic dermatology.

  12. Alternative splicing modulates stem cell differentiation.

    PubMed

    Fu, Ru-Huei; Liu, Shih-Ping; Ou, Chen-Wei; Yu, Hsiu-Hui; Li, Kuo-Wei; Tsai, Chang-Hai; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2009-01-01

    Stem cells have the surprising potential to develop into many different cell types. Therefore, major research efforts have focused on transplantation of stem cells and/or derived progenitors for restoring depleted diseased cells in degenerative disorders. Understanding the molecular controls, including alternative splicing, that arise during lineage differentiation of stem cells is crucial for developing stem cell therapeutic approaches in regeneration medicine. Alternative splicing to allow a single gene to encode multiple transcripts with different protein coding sequences and RNA regulatory elements increases genomic complexities. Utilizing differences in alternative splicing as a molecular marker may be more sensitive than simply gene expression in various degrees of stem cell differentiation. Moreover, alternative splicing maybe provide a new concept to acquire induced pluripotent stem cells or promote cell-cell transdifferentiation for restorative therapies and basic medicine researches. In this review, we highlight the recent advances of alternative splicing regulation in stem cells and their progenitors. It will hopefully provide much needed knowledge into realizing stem cell biology and related applications.

  13. Mesenchymal stem cells, aging and regenerative medicine

    PubMed Central

    Raggi, Chiara; Berardi, Anna C.

    2012-01-01

    Summary Tissue maintenance and regeneration is dependent on stem cells and increasing evidence has shown to decline with age. Stem cell based-aging is thought to influence therapeutic efficacy. Mesenchymal stromal cells (MSCs) are involved in tissue regeneration. Here, we discuss the effects of age-related changes on MSC properties considering their possible use in research or regenerative medicine. PMID:23738303

  14. Nanomaterials for Engineering Stem Cell Responses.

    PubMed

    Kerativitayanan, Punyavee; Carrow, James K; Gaharwar, Akhilesh K

    2015-08-05

    Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial-stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial-stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications.

  15. Stomach development, stem cells and disease.

    PubMed

    Kim, Tae-Hee; Shivdasani, Ramesh A

    2016-02-15

    The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms.

  16. Paediatric idiopathic limbal stem cell deficiency.

    PubMed

    Vincent, Stephen J; Lee, Graham A

    2017-03-20

    Acquired limbal stem cell deficiency (LSCD) describes a condition in which the corneal limbal stem cells are altered or destroyed, typically due to ocular trauma, chronic allergy or inflammation. Idiopathic LSCD is a term used to describe limbal stem cell failure in the absence of any identifiable causative factor. While several cases of adult-onset LSCD have been identified previously, this case report describes a rare presentation of bilateral asymmetric idiopathic paediatric limbal stem cell deficiency in a sixteen-year-old male with an otherwise unremarkable ocular history.

  17. Wnt Signaling in Cancer Stem Cell Biology

    PubMed Central

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  18. Genetic and epigenetic instability of stem cells.

    PubMed

    Rajamani, Karthyayani; Li, Yuan-Sheng; Hsieh, Dean-Kuo; Lin, Shinn-Zong; Harn, Horng-Jyh; Chiou, Tzyy-Wen

    2014-01-01

    Recently, research on stem cells has been receiving an increasing amount of attention, both for its advantages and disadvantages. Genetic and epigenetic instabilities among stem cells have been a recurring obstacle to progress in regenerative medicine using stem cells. Various reports have stated that these instabilities can transform stem cells when transferred in vivo and thus have the potential to develop tumors. Previous research has shown that various extrinsic and intrinsic factors can contribute to the stability of stem cells. The extrinsic factors include growth supplements, growth factors, oxygen tension, passage technique, and cryopreservation. Controlling these factors based on previous reports may assist researchers in developing strategies for the production and clinical application of "safe" stem cells. On the other hand, the intrinsic factors can be unpredictable and uncontrollable; therefore, to ensure the successful use of stem cells in regenerative medicine, it is imperative to develop and implement appropriate strategies and technique for culturing stem cells and to confirm the genetic and epigenetic safety of these stem cells before employing them in clinical trials.

  19. Pituitary stem cells: where do we stand?

    PubMed

    Vankelecom, Hugo; Chen, Jianghai

    2014-03-25

    Some 5 years ago, the stem cells of the adult pituitary gland were discovered. Subsequent in-depth characterization revealed expression of several stemness markers and embryo-typical factors. Now, the quest is open to decipher their role in the gland. When and how pituitary stem cells differentiate to contribute to the mature hormone-producing cell populations is not known. New research models support their involvement in cell regeneration after injury in the gland, and suggest a possible role in pituitary tumor formation. From their expression phenotype, pituitary stem cells seem to re-use embryonic developmental programs during the creation of new hormonal cells. Here, we will review the latest progression in the domain of pituitary stem cells, including the uncovering of some new molecular flavors and of the first potential functions. Eventually, we will speculate on their differentiation programs towards hormonal cells, with a particular focus on gonadotropes.

  20. Stem cell therapy for voiding and erectile dysfunction

    PubMed Central

    Vaegler, Martin; Lenis, Andrew T; Daum, Lisa; Renninger, M; Bastian, Amend; Stenzl, Arnulf; Damaser, Margot S; Sievert, Karl-Dietrich

    2013-01-01

    Voiding dysfunction comprises a variety of disorders, including stress urinary incontinence and overactive bladder, and affects millions of men and women worldwide. Erectile dysfunction (ED) also decreases quality of life for millions of men, as well as for their partners. Advanced age and diabetes are common comorbidities that can exacerbate and negatively impact upon the development of these disorders. Therapies that target the pathophysiology of these conditions to halt progression are not currently available. However, stem cell therapy could fill this therapeutic void. Stem cells can reduce inflammation, prevent fibrosis, promote angiogenesis, recruit endogenous progenitor cells, and differentiate to replace damaged cells. Adult multipotent stem cell therapy, in particular, has shown promise in case reports and preclinical animal studies. Stem cells have also enabled advances in urological tissue engineering by facilitating ex vivo construction of bladder wall and urethral tissue (using a patient's own cells) prior to transplantation. More recent studies have focused on bioactive factor secretion and homing of stem cells. In the future, clinicians are likely to utilize allogeneic stem cell sources, intravenous systemic delivery, and ex vivo cell enhancement to treat voiding dysfunction and ED. PMID:22710667

  1. Stem cells from amniotic fluid--Potential for regenerative medicine.

    PubMed

    Loukogeorgakis, Stavros P; De Coppi, Paolo

    2016-02-01

    Regenerative medicine has recently been established as an emerging field focussing on repair, replacement or regeneration of cells, tissues and whole organs. The significant recent advances in the field have intensified the search for novel sources of stem cells with potential for therapy. Recently, researchers have identified the amniotic fluid as an untapped source of stem cells that are multipotent, possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells. Stem cells from the amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, which make them an ideal candidate for tissue engineering applications. In addition, their ability to engraft in injured organs and modulate immune and repair responses of host tissues suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases affecting major tissues/organs. This review summarises the evidence on amniotic fluid cells over the past 15 years and explores the potential therapeutic applications of amniotic fluid stem cells and amniotic fluid mesenchymal stem cells.

  2. Stem cells for brain repair in neonatal hypoxia-ischemia.

    PubMed

    Chicha, L; Smith, T; Guzman, R

    2014-01-01

    Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

  3. Drosophila dyskerin is required for somatic stem cell homeostasis.

    PubMed

    Vicidomini, Rosario; Petrizzo, Arianna; di Giovanni, Annamaria; Cassese, Laura; Lombardi, Antonella Anna; Pragliola, Caterina; Furia, Maria

    2017-03-23

    Drosophila represents an excellent model to dissect the roles played by the evolutionary conserved family of eukaryotic dyskerins. These multifunctional proteins are involved in the formation of H/ACA snoRNP and telomerase complexes, both involved in essential cellular tasks. Since fly telomere integrity is guaranteed by a different mechanism, we used this organism to investigate the specific role played by dyskerin in somatic stem cell maintenance. To this aim, we focussed on Drosophila midgut, a hierarchically organized and well characterized model for stemness analysis. Surprisingly, the ubiquitous loss of the protein uniquely affects the formation of the larval stem cell niches, without altering other midgut cell types. The number of adult midgut precursor stem cells is dramatically reduced, and this effect is not caused by premature differentiation and is cell-autonomous. Moreover, a few dispersed precursors found in the depleted midguts can maintain stem identity and the ability to divide asymmetrically, nor show cell-growth defects or undergo apoptosis. Instead, their loss is mainly specifically dependent on defective amplification. These studies establish a strict link between dyskerin and somatic stem cell maintenance in a telomerase-lacking organism, indicating that loss of stemness can be regarded as a conserved, telomerase-independent effect of dyskerin dysfunction.

  4. Current Biosafety Considerations in Stem Cell Therapy

    PubMed Central

    Mousavinejad, Masoumeh; Andrews, Peter W.; Shoraki, Elham Kargar

    2016-01-01

    Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient’s life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies. PMID:27540533

  5. Lineage tracing quantification reveals symmetric stem cell division in Drosophila male germline stem cells.

    PubMed

    Salzmann, Viktoria; Inaba, Mayu; Cheng, Jun; Yamashita, Yukiko M

    2013-12-01

    In the homeostatic state, adult stem cells divide either symmetrically to increase the stem cell number to compensate stem cell loss, or asymmetrically to maintain the population while producing differentiated cells. We have investigated the mode of stem cell division in the testes of Drosophila melanogaster by lineage tracing and confirm the presence of symmetric stem cell division in this system. We found that the rate of symmetric division is limited to 1-2% of total germline stem cell (GSC) divisions, but it increases with expression of a cell adhesion molecule, E-cadherin, or a regulator of the actin cytoskeleton, Moesin, which may modulate adhesiveness of germ cells to the stem cell niche. Our results indicate that the decision regarding asymmetric vs. symmetric division is a dynamically regulated process that contributes to tissue homeostasis, responding to the needs of the tissue.

  6. Single-cell sequencing in stem cell biology.

    PubMed

    Wen, Lu; Tang, Fuchou

    2016-04-15

    Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

  7. Nonclinical safety strategies for stem cell therapies

    SciTech Connect

    Sharpe, Michaela E.; Morton, Daniel; Rossi, Annamaria

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  8. Cancer stem cells in glioblastoma

    PubMed Central

    Lathia, Justin D.; Mack, Stephen C.; Mulkearns-Hubert, Erin E.; Valentim, Claudia L.L.; Rich, Jeremy N.

    2015-01-01

    Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial. PMID:26109046

  9. Increased proteasome activity determines human embryonic stem cell identity

    PubMed Central

    Vilchez, David; Boyer, Leah; Morantte, Ianessa; Lutz, Margaret; Merkwirth, Carsten; Joyce, Derek; Spencer, Brian; Page, Lesley; Masliah, Eliezer; Berggren, W. Travis; Gage, Fred H.; Dillin, Andrew

    2016-01-01

    Embryonic stem cells are able to replicate continuously in the absence of senescence and, therefore, are immortal in culture1,2. While genome stability is central for survival of stem cells; proteome stability may play an equally important role in stem cell identity and function. Additionally, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. We hypothesized that stem cells have an increased proteostasis ability compared to their differentiated counterparts and asked whether proteasome activity differed among human embryonic stem cells (hESCs). Notably, hESC populations exhibit a high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11/RPN-63–5 and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. Proteasome inhibition affects pluripotency of hESCs inducing differentiation towards specific cell lineages. FOXO4, an insulin/IGF-1 responsive transcription factor associated with long lifespan in invertebrates6,7, regulates proteasome activity by modulating the expression of PSMD11 in hESCs. Our results establish a novel regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates with hESC function and identity. PMID:22972301

  10. Arsenic Exposure Transforms Human Epithelial Stem/Progenitor Cells into a Cancer Stem-like Phenotype

    PubMed Central

    Tokar, Erik J.; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2010-01-01

    Background Inorganic arsenic is a ubiquitous environmental carcinogen affecting millions of people worldwide. Evolving theory predicts that normal stem cells (NSCs) are transformed into cancer stem cells (CSCs) that then drive oncogenesis. In humans, arsenic is carcinogenic in the urogenital system (UGS), including the bladder and potentially the prostate, whereas in mice arsenic induces multiorgan UGS cancers, indicating that UGS NSCs may represent targets for carcinogenic initiation. However, proof of emergence of CSCs induced by arsenic in a stem cell population is not available. Methods We continuously exposed the human prostate epithelial stem/progenitor cell line WPE-stem to an environmentally relevant level of arsenic (5 μM) in vitro and determined the acquired cancer phenotype. Results WPE-stem cells rapidly acquired a malignant CSC-like phenotype by 18 weeks of exposure, becoming highly invasive, losing contact inhibition, and hypersecreting matrix metalloproteinase-9. When hetero-transplanted, these cells (designated As-CSC) formed highly pleomorphic, aggressive tumors with immature epithelial- and mesenchymal-like cells, suggesting a highly pluripotent cell of origin. Consistent with tumor-derived CSCs, As-CSCs formed abundant free-floating spheres enriched in CSC-like cells, as confirmed by molecular analysis and the fact that only these floating cells formed xenograft tumors. An early loss of NSC self-renewal gene expression (p63, ABCG2, BMI-1, SHH, OCT-4, NOTCH-1) during arsenite exposure was subsequently reversed as the tumor suppressor gene PTEN was progressively suppressed and the CSC-like phenotype acquired. Conclusions Arsenite transforms prostate epithelial stem/progenitor cells into CSC-like cells, indicating that it can produce CSCs from a model NSC population. PMID:20056578

  11. [Prenatal stem cell transplantation: from bench to bedside].

    PubMed

    Surbek, D V; Holzgreve, W

    2002-11-01

    Prenatal stem cell transplantation is a novel, promising therapeutic option for genetic disorders, which is now at the edge of moving from preclinical research into clinical application. The first clinical experience shows that inborn diseases, which lead to a severe immunodeficiency, can be treated successfully inutero. No therapeutic success has been achieved in genetic disorders which do not severely affect the immune system. Therefore, new strategies to improve the success are being developed, including e.g., graft modification, prenatal conditioning of the fetus, postnatal re-transplantation after prenatal induction of immune tolerance, and fetal gene therapy using autologous fetal stem cells. The use of non-hematopoietic (e.g. mesenchymal) or pluripotent stem cells will most probably lead to an expansion of the spectrum of indications in genetic diseases for this novel treatment. At the same time, however, ethical implications, in particular regarding fetal gene therapy and the use of pluripotent stem cells must be evaluated.

  12. Stem cell approaches in psychiatry--challenges and opportunities.

    PubMed

    Benninghoff, Jens

    2009-01-01

    Exploring stem cells is a fascinating task, especially in a discipline where the use of stem cells seems far-fetched at first glance, as is the case in psychiatry. In this article we would like to provide a brief overview of the current situation in relation to the treatment of mental diseases. For reasons that we will explain, this review will focus on affective disorders. The following section will give a more detailed account of stem-cell biology including current basic science approaches presenting in-vivo and in-vitro techniques. The final part will then look into future perspectives of using these stem cells to cure mental illnesses, and discuss the related challenges and opportunities.

  13. Composition of Mineral Produced by Dental Mesenchymal Stem Cells

    PubMed Central

    Volponi, A.A.; Gentleman, E.; Fatscher, R.; Pang, Y.W.Y.; Gentleman, M.M.; Sharpe, P.T.

    2015-01-01

    Mesenchymal stem cells isolated from different dental tissues have been described to have osteogenic/odontogenic-like differentiation capacity, but little attention has been paid to the biochemical composition of the material that each produces. Here, we used Raman spectroscopy to analyze the mineralized materials produced in vitro by different dental cell populations, and we compared them with the biochemical composition of native dental tissues. We show that different dental stem cell populations produce materials that differ in their mineral and matrix composition and that these differ from those of native dental tissues. In vitro, BCMP (bone chip mass population), SCAP (stem cells from apical papilla), and SHED (stem cells from human-exfoliated deciduous teeth) cells produce a more highly mineralized matrix when compared with that produced by PDL (periodontal ligament), DPA (dental pulp adult), and GF (gingival fibroblast) cells. Principal component analyses of Raman spectra further demonstrated that the crystallinity and carbonate substitution environments in the material produced by each cell type varied, with DPA cells, for example, producing a more carbonate-substituted mineral and with SCAP, SHED, and GF cells creating a less crystalline material when compared with other dental stem cells and native tissues. These variations in mineral composition reveal intrinsic differences in the various cell populations, which may in turn affect their specific clinical applications. PMID:26253190

  14. Enhancing spontaneous stem cell healing (Review)

    PubMed Central

    MAGUIRE, GREG; FRIEDMAN, PETER

    2014-01-01

    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

  15. Glial cell derived neurotrophic factor induces spermatogonial stem cell marker genes in chicken mesenchymal stem cells.

    PubMed

    Boozarpour, Sohrab; Matin, Maryam M; Momeni-Moghaddam, Madjid; Dehghani, Hesam; Mahdavi-Shahri, Naser; Sisakhtnezhad, Sajjad; Heirani-Tabasi, Asieh; Irfan-Maqsood, Muhammad; Bahrami, Ahmad Reza

    2016-06-01

    Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage differentiation. Advances in differentiation technology have also resulted in the conversion of MSCs to other kinds of stem cells. MSCs are considered as a suitable source of cells for biotechnology purposes because they are abundant, easily accessible and well characterized cells. Nowadays small molecules are introduced as novel and efficient factors to differentiate stem cells. In this work, we examined the potential of glial cell derived neurotrophic factor (GDNF) for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were isolated and characterized from chicken and cultured under treatment with all-trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression analysis of specific genes after 7days of RA treatment, as examined by RT-PCR, proved positive for some germ cell markers such as CVH, STRA8, PLZF and some genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as well as other genes which were induced after RA treatment. These data illustrated that GDNF is relatively more effective in diverting chicken MSCs towards Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent to obtain transgenic poultry, nevertheless, exploitability of these cells should be verified by more experiments.

  16. Stem cells of the skin epithelium

    PubMed Central

    Alonso, Laura; Fuchs, Elaine

    2003-01-01

    Tissue stem cells form the cellular base for organ homeostasis and repair. Stem cells have the unusual ability to renew themselves over the lifetime of the organ while producing daughter cells that differentiate into one or multiple lineages. Difficult to identify and characterize in any tissue, these cells are nonetheless hotly pursued because they hold the potential promise of therapeutic reprogramming to grow human tissue in vitro, for the treatment of human disease. The mammalian skin epithelium exhibits remarkable turnover, punctuated by periods of even more rapid production after injury due to burn or wounding. The stem cells responsible for supplying this tissue with cellular substrate are not yet easily distinguishable from neighboring cells. However, in recent years a significant body of work has begun to characterize the skin epithelial stem cells, both in tissue culture and in mouse and human skin. Some epithelial cells cultured from skin exhibit prodigious proliferative potential; in fact, for >20 years now, cultured human skin has been used as a source of new skin to engraft onto damaged areas of burn patients, representing one of the first therapeutic uses of stem cells. Cell fate choices, including both self-renewal and differentiation, are crucial biological features of stem cells that are still poorly understood. Skin epithelial stem cells represent a ripe target for research into the fundamental mechanisms underlying these important processes. PMID:12913119

  17. Transdifferentiation of Stem Cells: A Critical View

    NASA Astrophysics Data System (ADS)

    Gruh, Ina; Martin, Ulrich

    Recently a large amount of new data on the plasticity of stem cells of various lineages have emerged, providing new perspectives especially for the therapeutic application of adult stem cells. Previously unknown possibilities of cell differentiation beyond the known commitment of a given stem cell have been described using keywords such as "blood to liver," or "bone to brain." Controversies on the likelihood, as well as the biological significance, of these conversions almost immediately arose within this young field of stem cell biology. This chapter will concentrate on these controversies and focus on selected examples demonstrating the technical aspects of stem cell transdifferentiation and the evaluation of the tools used to analyze these events.

  18. Structural properties of scaffolds: Crucial parameters towards stem cells differentiation

    PubMed Central

    Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Tian, Lingling; Shamirzaei-Jeshvaghani, Elham; Dehghani, Leila; Ramakrishna, Seeram

    2015-01-01

    Tissue engineering is a multidisciplinary field that applies the principles of engineering and life-sciences for regeneration of damaged tissues. Stem cells have attracted much interest in tissue engineering as a cell source due to their ability to proliferate in an undifferentiated state for prolonged time and capability of differentiating to different cell types after induction. Scaffolds play an important role in tissue engineering as a substrate that can mimic the native extracellular matrix and the properties of scaffolds have been shown to affect the cell behavior such as the cell attachment, proliferation and differentiation. Here, we focus on the recent reports that investigated the various aspects of scaffolds including the materials used for scaffold fabrication, surface modification of scaffolds, topography and mechanical properties of scaffolds towards stem cells differentiation effect. We will present a more detailed overview on the effect of mechanical properties of scaffolds on stem cells fate. PMID:26029344

  19. Isolation and Culture of Embryonic Stem Cells, Mesenchymal Stem Cells, and Dendritic Cells from Humans and Mice.

    PubMed

    Kar, Srabani; Mitra, Shinjini; Banerjee, Ena Ray

    2016-01-01

    Stem cells are cells capable of proliferation, self-renewal, and differentiation into specific phenotypes. They are an essential part of tissue engineering, which is used in regenerative medicine in case of degenerative diseases. In this chapter, we describe the methods of isolating and culturing various types of stem cells, like human embryonic stem cells (hESCs), human umbilical cord derived mesenchymal stem cells (hUC-MSCs), murine bone marrow derived mesenchymal stem cells (mBM-MSCs), murine adipose tissue derived mesenchymal stem cells (mAD-MSCs), and murine bone marrow derived dendritic cells (mBMDCs). All these cell types can be used in tissue engineering techniques.

  20. Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics

    PubMed Central

    Lin, Sabrina C.; Bays, Brett C.; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

    2016-01-01

    There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells. PMID:26848582

  1. Neural stem cells: from neurobiology to clinical applications.

    PubMed

    Andressen, Christian

    2013-01-01

    In spite of increasing numbers of publications about cell replacement therapies in various neurodegenerative diseases, reports on therapeutic benefits are still rare due to the huge array of parameters affecting the clinically relevant outcome. Limiting conditions can be attributed to origin and number of cells used for transplantation, their in vitro storage, propagation and/or predifferentiation. In addition, the ability of these cells for a site directed differentiation and functional integration in sufficient numbers is known to depend on extrinsic factors including intracerebral position of graft(s). Thus, obstacles to the use of cells in replacement therapies of neurological disorders reflect the molecular as well as cellular complexity of affected functional systems. This review will highlight central aspects of cell replacement strategies that are currently regarded as the most limiting issues in respect to survival, cell identity and site directed differentiation as well as functional integration of grafts. Special attention will be paid to neural stem cells, derived from either fetal or adult central nervous tissue. Unravelling the molecular biology of these proliferating cells in combination with instructive environmental cues for their site directed differentiation will pave the way to high reproducibility in collection, propagation, and predifferentiation of transplantable cells in vitro. In addition, this knowledge of intrinsic and extrinsic cues for a site directed neural differentiation during development will broaden the perspective for any pluripotent stem cell, namely embryonic stem and induced pluripotent stem cells, as an alternate source for a cell based therapy of neurodegenerative diseases.

  2. Epigenetic targeting of ovarian cancer stem cells.

    PubMed

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer.

  3. Epigenetic Targeting of Ovarian Cancer Stem Cells

    PubMed Central

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P.; Matei, Daniela

    2014-01-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer (OC). As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cell (OCSC). In this study, we tested the hypothesis that DNA hypomethylating agents may be able to reset OCSC towards a differentiated phenotype, by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH+ OC cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low dose SGI-110 reduced the stem-like properties of ALDH+ cells, including their tumor initiating capacity, resensitized these OCSCs to platinum, and induced re-expression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by re-programming residual cancer stem-like cells. Further, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  4. Improving Stem Cell Therapeutics with Mechanobiology

    PubMed Central

    Shin, Jae-Won; Mooney, David J.

    2017-01-01

    In recent years, it has become clear that mechanical cues play an integral role in maintaining stem cell functions. Here we discuss how integrating physical approaches and engineering principles in stem cell biology, including culture systems, preclinical models, and functional assessment, may improve clinical application in regenerative medicine. PMID:26748752

  5. Stem Cell Research and Health Education

    ERIC Educational Resources Information Center

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2008-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the…

  6. Representations of stem cell clinics on Twitter.

    PubMed

    Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

    2014-12-01

    The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients.

  7. Stem Cell Transplants in Cancer Treatment

    Cancer.gov

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  8. Stem cell banking: between traceability and identifiability.

    PubMed

    Knoppers, Bartha M; Isasi, Rosario

    2010-10-05

    Stem cell banks are increasingly seen as an essential resource of biological materials for both basic and translational research. Stem cell banks support transnational access to quality-controlled and ethically sourced stem cell lines from different origins and of varying grades. According to the Organisation for Economic Co-operation and Development, advances in regenerative medicine are leading to the development of a bioeconomy, 'a world where biotechnology contributes to a significant share of economic output'. Consequently, stem cell banks are destined to constitute a pillar of the bioeconomy in many countries. While certain ethical and legal concerns are specific to the nature of stem cells, stem cell banking could do well to examine the approaches fostered by tissue banking generally. Indeed, the past decade has seen a move to simplify and harmonize biological tissue and data banking so as to foster international interoperability. In particular, the issues of consent and of traceability illustrate not only commonalities but the opportunity for stem cell banking to appreciate the lessons learned in biobanking generally. This paper analyzes convergence and divergence in issues surrounding policy harmonization, transnational sharing, informed consent, traceability and return of results in the context of stem cell banks.

  9. Pathological modifications of plant stem cell destiny

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

  10. Organ or Stem Cell Transplant and Your Mouth

    MedlinePlus

    ... Stem Cell Transplant and Your Mouth Organ or Stem Cell Transplant and Your Mouth Main Content Key Points​ ... Your Dentist Before Transplant Before an organ or stem cell transplant, have a dental checkup. Your mouth should ...

  11. Programming the genome in embryonic and somatic stem cells.

    PubMed

    Collas, Philippe; Noer, Agate; Timoskainen, Sanna

    2007-01-01

    In opposition to terminally differentiated cells, stem cells can self-renew and give rise to multiple cell types. Embryonic stem cells retain the ability of the inner cell mass of blastocysts to differentiate into all cell types of the body and have acquired in culture unlimited self-renewal capacity. Somatic stem cells are found in many adult tissues, have an extensive but finite lifespan and can differentiate into a more restricted array of cell types. A growing body of evidence indicates that multi-lineage differentiation ability of stem cells can be defined by the potential for expression of lineage-specification genes. Gene expression, or as emphasized here, potential for gene expression, is largely controlled by epigenetic modifications of DNA and chromatin on genomic regulatory and coding regions. These modifications modulate chromatin organization not only on specific genes but also at the level of the whole nucleus; they can also affect timing of DNA replication. This review highlights how mechanisms by which genes are poised for transcription in undifferentiated stem cells are being uncovered through primarily the mapping of DNA methylation, histone modifications and transcription factor binding throughout the genome. The combinatorial association of epigenetic marks on developmentally regulated and lineage-specifying genes in undifferentiated cells seems to define a pluripotent state.

  12. Computational Tools for Stem Cell Biology.

    PubMed

    Bian, Qin; Cahan, Patrick

    2016-12-01

    For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the past several years, a new subdiscipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate.

  13. Cancer Stem Cells: Repair Gone Awry?

    PubMed Central

    Rangwala, Fatima; Omenetti, Alessia; Diehl, Anna Mae

    2011-01-01

    Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on this process, and thus may unmask defective regulation of pathways, such as Hedgehog (Hh), that modulate progenitor cell fate. Hh pathway dysregulation has been demonstrated in many types of cancer, including pancreatic and liver cancers, in which defective Hh signaling has been linked to outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements. Hence, the Hh pathway might be a therapeutic target in such tumors. PMID:21188169

  14. Clinical trials for stem cell transplantation: when are they needed?

    PubMed

    Van Pham, Phuc

    2016-04-27

    In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.

  15. [Application prospect of adult stem cells in male infertility].

    PubMed

    Yang, Rui-Feng; Xiong, Cheng-Liang

    2013-05-01

    The study on stem cells is a hot field in biomedical science in recent years, and has furthered from laboratory to clinical application. Stem cells, according to their developmental stage and differential properties, can be divided into embryonic stem cells, induced PS cells and adult stem cells, among which, adult stem cells have already been applied to the clinical treatment of many systemic diseases. Currently, the study of spermatogonial stem cells and adult stem cells is in the front of the basic researches on the treatment of male infertility, but the time has not yet arrived for their clinical application. This paper outlines the application prospect of adult stem cells in male infertility.

  16. CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches.

    PubMed

    Williams, Karin; Motiani, Karan; Giridhar, Premkumar Vummidi; Kasper, Susan

    2013-03-01

    The stem cell niche provides a regulatory microenvironment for cells as diverse as totipotent embryonic stem cells to cancer stem cells (CSCs) which exhibit stem cell-like characteristics and have the capability of regenerating the bulk of tumor cells while maintaining self-renewal potential. The transmembrane glycoprotein CD44 is a common component of the stem cell niche and exists as a standard isoform (CD44s) and a range of variant isoforms (CD44v) generated though alternative splicing. CD44 modulates signal transduction through post-translational modifications as well as interactions with hyaluronan, extracellular matrix molecules and growth factors and their cognate receptor tyrosine kinases. While the function of CD44 in hematopoietic stem cells has been studied in considerable detail, our knowledge of CD44 function in tissue-derived stem cell niches remains limited. Here we review CD44s and CD44v in both hematopoietic and tissue-derived stem cell niches, focusing on their roles in regulating stem cell behavior including self-renewal and differentiation in addition to cell-matrix interactions and signal transduction during cell migration and tumor progression. Determining the role of CD44 and CD44v in normal stem cell, CSC and (pre)metastatic niches and elucidating their unique functions could provide tools and therapeutic strategies for treating diseases as diverse as fibrosis during injury repair to cancer progression.

  17. [Stem cells--cloning, plasticity, bioethic].

    PubMed

    Pflegerl, Pamina; Keller, Thomas; Hantusch, Brigitte; Hoffmann, Thomas Sören; Kenner, Lukas

    2008-01-01

    Stem cells with certain characteristics have become promising tools for molecular medicine. They have the potential to self-regenerate and to differentiate into specific tissues. Besides their great potential, embryonic stem cells (ESC) run the risk of enhanced tumorigenesis. The use of human embryonic stem cells (hESC) is ethically problematic because their isolation involves the destruction of human embryos. Recently developed methods generate are able to pluripotent stem cells from fibroblasts. Alternatives for ESC are adult stem cells (ASC) derived from bone marrow, cord blood, amniotic fluid and other tissues. The following article is on the basis of testimony of Lukas Kenner for the German Bundestag about the use of ESC for research, therapy and drug development. Ethical aspects are taken into consideration.

  18. [Biological properties of spermatogonial stem cell niches].

    PubMed

    Li, Ling-Ling; Liu, Yang; Jin, Bo; Zhang, Xue-Ming

    2012-04-01

    The self-renewal and differentiation of adult stem cells are closely related to their niches. Naturally, spermatogonial stem cells (SSCs) are the only adult stem cells in the body, which can transfer genetic information into the offspring. An insight into the modulation of the self-renewal and differentiation of SSCs can help elucidate the mechanisms of spermatogenesis and investigate the proliferation and differentiation of other adult stem cells. Therefore, the SSC system provides an ideal model for researches on the adult stem cell niche. More and more evidence indicates that the self-renewal and differentiation of SSCs are regulated by their niches. Based on our previous work and other related findings recently reported, this article presents an overview on the biological properties of SSC niches and their relationship with the self-renewal and differentiation of SSCs, focusing on the basic properties and components of SSC niches and various regulatory factors they produce.

  19. Planarians, a tale of stem cells.

    PubMed

    Rossi, L; Salvetti, A; Batistoni, R; Deri, P; Gremigni, V

    2008-01-01

    Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues.

  20. Functional ion channels in stem cells

    PubMed Central

    Li, Gui-Rong; Deng, Xiu-Ling

    2011-01-01

    Bioelectrical signals generated by ion channels play crucial roles in excitation genesis and impulse conduction in excitable cells as well as in cell proliferation, migration and apoptosis in proliferative cells. Recent studies have demonstrated that multiple ion channels are heterogeneously present in different stem cells; however, patterns and phenotypes of ion channels are species- and/or origin-dependent. This editorial review focuses on the recent findings related to the expression of functional ion channels and the roles of these channels in regulation of cell proliferation in stem cells. Additional effort is required in the future to clarify the ion channel expression in different types of stem cells; special attention should be paid to the relationship between ion channels and stem cell proliferation, migration and differentiation. PMID:21607133

  1. Pluripotent Stem Cells and Gene Therapy

    PubMed Central

    Simara, Pavel; Motl, Jason A.; Kaufman, Dan S.

    2013-01-01

    Human pluripotent stem cells represent an accessible cell source for novel cell-based clinical research and therapies. With the realization of induced pluripotent stem cells (iPSCs), it is possible to produce almost any desired cell type from any patient's cells. Current developments in gene modification methods have opened the possibility for creating genetically corrected human iPSCs for certain genetic diseases that could be used later in autologous transplantation. Promising preclinical studies have demonstrated correction of disease-causing mutations in a number of hematological, neuronal and muscular disorders. This review aims to summarize these recent advances with a focus on iPSC generation techniques, as well as gene modification methods. We will then further discuss some of the main obstacles remaining to be overcome before successful application of human pluripotent stem cell-based therapy arrives in the clinic and what the future of stem cell research may look like. PMID:23353080

  2. An introduction to induced pluripotent stem cells.

    PubMed

    Hanley, Joanna; Rastegarlari, Ghasem; Nathwani, Amit C

    2010-10-01

    Recent landmark studies show that it is now possible to convert somatic cells, such as skin fibroblasts and B lymphocytes, into pluripotent stem cells that closely resemble embryonic stem cells. These induced pluripotent stem (iPS) cells can be generated without using human embryos or oocytes, thus bypassing some of the ethical issues that have limited the use of human embryonic stems (hES) cells. Additionally, they can be derived from the patient to be treated, thereby overcoming problems of immunological rejection associated with the use of allogeneic hES cell derived progenitors. Whilst these patient-specific iPS cells have great clinical potential, their immediate utility is likely to be in drug screening and for understanding the disease process. This review discusses the promise of iPS cells as well as the challenges to their use in the clinic.

  3. Translational research of adult stem cell therapy.

    PubMed

    Suzuki, Gen

    2015-11-26

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  4. Breast cancer stem cells and radiation

    NASA Astrophysics Data System (ADS)

    Phillips, Tiffany Marie

    2007-12-01

    The present studies explore the response of breast cancer stem cells (BCSC's) to radiation and the implications for clinical cancer treatment. Current cancer therapy eliminates bulky tumor mass but may fail to eradicate a critical tumor initiating cell population termed "cancer stem cells". These cells are potentially responsible for tumor formation, metastasis, and recurrence. Recently cancer stem cells have been prospectively identified in various malignancies, including breast cancer. The breast cancer stem cell has been identified by the surface markers CD44+/CD24 -(low). In vitro mammosphere cultures allow for the enrichment of the cancer stem cell population and were utilized in order to study differential characteristics of BCSC's. Initial studies found that BCSC's display increased radiation resistance as compared to other non-stem tumor cells. This resistance was accompanied by decreased H2AX phosphorylation, decreased reactive oxygen species formation, and increased phosphorylation of the checkpoint protein Chk1. These studies suggest differential DNA damage and repair within the BCSC population. Studies then examined the consequences of fractionated radiation on the BCSC population and found a two-fold increase in BCSC's following 5 x 3Gy. This observation begins to tie cancer stem cell self-renewal to the clinical stem cell phenomenon of accelerated repopulation. Accelerated repopulation is observed when treatment gaps increase between sequential fractions of radiotherapy and may be due to cancer stem cell symmetric self-renewal. The balance between asymmetric and symmetric stem cell division is vital for proper maintenance; deregulation is likely linked to cancer initiation and progression. The developmental Notch-1 pathway was found to regulate BCSC division. Over-expressing the constitutively active Notch-1-ICD in MCF7 cells produced an increase in the BCSC population. Additionally, radiation was observed to increase the expression of the Notch-1

  5. Stem cells and liver engineering.

    PubMed

    Ordovás, Laura; Park, Yonsil; Verfaillie, Catherine M

    2013-11-15

    Human hepatocytes, suitable for treatment of patients with liver failure, for the creation of bioartificial (BAL) devices, or for studies for toxicity and metabolization studies in the pharmaceutical industry, are in short supply due to the lack of donor organs. Therefore, methods that allow ex vivo expansion of hepatocytes with mature function are being pursued. One cell source, believed to be a possible inexhaustible source of hepatocytes, is pluripotent stem cells (PSCs). However, directed differentiation of PSCs to cells with features of adult hepatocytes is not yet possible. Differentiated progeny remains mixed and PSC progeny does not have a number of the functional features of mature hepatocytes. In this review article, we will address tools being developed that allow for the identification of mature hepatocytes, in a non-invasive manner; to perform lineage tracing of PSC progeny; and novel culture systems being created for the in vitro differentiation of PSCs to hepatocyte like cells, and for the maintenance of primary liver derived hepatocytes or PSC-derived hepatic progeny in culture. As conventional two-dimensional (2D) static culture conditions poorly recapitulate the in vivo cellular environment, we will discuss bioreactor systems for liver tissue engineering, both macro-scale and micro-scale culture systems.

  6. Stem cells from oral niches: a review

    PubMed Central

    Giordano, Guido; La Monaca, Gerardo; Annibali, Susanna; Cicconetti, Andrea; Ottolenghi, Livia

    2011-01-01

    Summary Aim Stem cell research in recent years have been considered the most advanced sort of medical-scientific research and early results have aroused great expectations. Also in dentistry many studies were performed with the final aim of obtaining new bone and new teeth. In this work we describe the state of the art in dental science stem cell research. Methods We have performed a web-based research on MEDLINE within (www.pubmed.gov). We have used “stem cells from human exfoliated deciduous teeth” (24 paper found), “periodontal ligament stem cells” (32 paper found), “stem cell apical papilla” (16 paper found), “dental pulp stem cells” (136 paper found) as keywords for research. For each keyword we have performed a complete review focusing on knowledge upgrade. Results For each topic was created a selection of papers in chronological order of publication date so to give a timetable of the development of the research for each niche. Conclusion Research about stem cell from oral niches began in 2000 and every year papers publicated were more than the precedent. This review analysed about 180 articles most of which in the last 5 years. Dentla pulp from adult as from deciduous teeth seems to be the most valuable font of stem cells due to the pluripotential type of cells. PMID:22238715

  7. Stem cell death and survival in heart regeneration and repair

    PubMed Central

    Kalvelyte, Audrone; Stulpinas, Aurimas; de Carvalho, Katherine Athayde Teixeira; Guarita-Souza, Luiz Cesar; Foldes, Gabor

    2016-01-01

    Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function. PMID:26687129

  8. [Stem cells of mammalian brain: biology of the stem cells in vivo and in vitro].

    PubMed

    Viktorov, I V

    2001-01-01

    Stem cells are totipotent cells of the blastocyst (embryonal stem cells) and multipotent germinative cells of ento-, ecto-, and mesoderm that give rise to all tissues during embryogenesis. The stem cells have high proliferation activity and an unlimited capacity for self-production by symmetrical mitosis. Asymmetrical mitosis of the stem cells generates daughter cells ("progenitor cells") with unlimited proliferation potential. During differentiation, the progenitor cells give rise to definitive somatic cells. The stem and progenitor cells are preserved in most tissues of adult organism and provide for the constant replacement of the cells after their physiological death and damage. At the end of last century, stem cells were found in the brain of the adult mouse and rat and later in the brain of other mammals including humans. The subependymal zone of the lateral ventricles is considered the site of stem cells localization; however, there are indications of stem cells origination from ependyma while the subependymal zone serves as a collector of the progenitor cells where these cells divide. The problem of the localization of stem cells in a mature brain has not yet been resolved and is actively discussed. The stem and progenitor cells, as well as neuro- and gliogenesis, are most explored in the hippocampus and olfactory bulb. The progenitor cells migrate to the olfactory bulb from the subependymal zone of the lateral ventricles via a rostral migratory stream formed by the astrocytes, and then they differentiate to neural and glial cells. In the hippocampus, the neurons are formed in the subgranular zone of dentate gyrus. The discovery of stem and progenitor cells in the mature brain and their subsequent investigation point to an ongoing neuro- and gliogenesis in all periventricular sections of the brain and spinal cord during the whole animal or human lifespan. These processes proved to be related to the functional condition of CNS, and the de novo formed neural

  9. Regenerative medicine for the kidney: renotropic factors, renal stem/progenitor cells, and stem cell therapy.

    PubMed

    Maeshima, Akito; Nakasatomi, Masao; Nojima, Yoshihisa

    2014-01-01

    The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.

  10. Stem cell approaches in psychiatry - challenges and opportunities

    PubMed Central

    Benninghoff, Jens

    2009-01-01

    Exploring stem ceils is a fascinating task, especially in a discipline where the use of stem cells seems far-fetched at first glance, as is the case in psychiatry. In this article we would like to provide a brief overview of the current situation in relation to the treatment of mental diseases. For reasons that we will explain, this review will focus on affective disorders. The following section will give a more detailed account of stem-cell biology, including current basic science approaches presenting in-vivo andin-vitro techniques. The final part will then look into future perspectives of using these stem cells to cure mental illnesses, and discuss the related challenges and opportunities. PMID:20135897

  11. Semiquantitative measure of immune responses against erythropoietic stem cell antigens

    SciTech Connect

    Harrison, D.E.

    1987-01-01

    A semiquantitative assay was developed and used to measure the effects of immune responses against 16 independent non-H-2 antigenic loci on erythropoietic stem cells. The assay compares repopulation in genetically anemic WBB6F1-W/Wv recipients that have normal immune responses, and in lethally irradiated WBB6F1 +/+ mice whose immune responses are suppressed by the irradiation. The differences in repopulating ability between these two types of recipients measure how immune responses affect erythropoietic stem cells. Stem cell repopulating abilities for the cells with antigens specified by the Thy-1, H-1, H-24, Ly-1, H-37, and H-17 loci were affected slightly, if at all. Repopulating abilities were moderately reduced by responses against antigens specified by H-15, 16, Ea-2, and Ly-2, 3 loci, and against the differences between the B6 and B10 genotypes, although marrow of these types cured W/Wv recipients. A surprising result occurred for the antigen specified by the H-8 locus, in which immune responses strongly reduced repopulating abilities, although this type of marrow cell cured W/Wv recipients. A comparison of these results with skin graft survival times suggests that the antigens specified by the H-17 and H-24 loci are strongly immunogenic on skin but not on marrow stem cells, while those specified by the H-12 and H-8 loci are strongly immunogenic on marrow stem cells but not on skin.

  12. Guided migration of neural stem cells derived from human embryonic stem cells by an electric field.

    PubMed

    Feng, Jun-Feng; Liu, Jing; Zhang, Xiu-Zhen; Zhang, Lei; Jiang, Ji-Yao; Nolta, Jan; Zhao, Min

    2012-02-01

    Small direct current (DC) electric fields (EFs) guide neurite growth and migration of rodent neural stem cells (NSCs). However, this could be species dependent. Therefore, it is critical to investigate how human NSCs (hNSCs) respond to EF before any possible clinical attempt. Aiming to characterize the EF-stimulated and guided migration of hNSCs, we derived hNSCs from a well-established human embryonic stem cell line H9. Small applied DC EFs, as low as 16 mV/mm, induced significant directional migration toward the cathode. Reversal of the field polarity reversed migration of hNSCs. The galvanotactic/electrotactic response was both time and voltage dependent. The migration directedness and distance to the cathode increased with the increase of field strength. (Rho-kinase) inhibitor Y27632 is used to enhance viability of stem cells and has previously been reported to inhibit EF-guided directional migration in induced pluripotent stem cells and neurons. However, its presence did not significantly affect the directionality of hNSC migration in an EF. Cytokine receptor [C-X-C chemokine receptor type 4 (CXCR4)] is important for chemotaxis of NSCs in the brain. The blockage of CXCR4 did not affect the electrotaxis of hNSCs. We conclude that hNSCs respond to a small EF by directional migration. Applied EFs could potentially be further exploited to guide hNSCs to injured sites in the central nervous system to improve the outcome of various diseases.

  13. From adult stem cells to cancer stem cells: Oct-4 Gene, cell-cell communication, and hormones during tumor promotion.

    PubMed

    Trosko, James E

    2006-11-01

    Carcinogenesis is characterized by "initiation," "promotion," and "progression" phases. The "stem cell theory" and "de-differentiation" theories are used to explain the origin of cancer. Growth control for stem cells, which lack functional gap junctional intercellular communication (GJIC), involves negative soluble or niche factors, while for progenitor cells, it involves GJIC. Tumor promoters, hormones, and growth factors inhibit GJIC reversibly. Oncogenes stably inhibit GJIC. Cancer cells, which lack growth control and the ability to terminally differentiate and to apoptose, lack GJIC. The Oct3/4 gene, a POU (Pit-Oct-Unc) family of transcription factors was thought to be expressed only in embryonic stem cells and in tumor cells. With the availability of normal adult human stem cells, tests for the expression of Oct3/4 gene and the stem cell theory in human carcinogenesis became possible. Human breast, liver, pancreas, kidney, mesenchyme, and gastric stem cells, HeLa and MCF-7 cells, and canine tumors were tested with antibodies and polymerase chain reaction (PCR) primers for Oct3/4. Adult human breast stem cells, immortalized nontumorigenic and tumor cell lines, but not the normal differentiated cells, expressed Oct3/4. Adult human differentiated cells lose their Oct-4 expression. Oct3/4 is expressed in a few cells found in the basal layer of human skin epidermis. The data demonstrate that normal adult stem cells and cancer stem cells maintain expression of Oct3/4, consistent with the stem cell hypothesis of carcinogenesis. These Oct-4 positive cells might represent the "cancer stem cells." A strategy to target "cancer stem cells" is to suppress the Oct-4 gene in order to cause the cells to differentiate.

  14. Stem cells and regeneration in planarians.

    PubMed

    Handberg-Thorsager, Mette; Fernandez, Enrique; Salo, Emili

    2008-05-01

    Understanding stem cells is a major goal of current research because of its potential medical applications. Although great advances have been made, such as the culturing and differentiation of embryonic stem cells and reprogramming of cell fates, many basic questions remain unanswered. Describing the mechanisms underlying regeneration will help to understand the biology of stem cells and therefore to control their behavior. While regeneration is being studied in a variety of models, the planarian is particularly noteworthy. In this model system a fragment as small as 1/279 of the animal can regenerate completely within a few weeks. These animals can also grow and degrow--specifically degenerating certain tissues--according to environmental conditions, thus demonstrating a complete control of their stem cell dynamics. However, one of the most interesting aspects of the planarian model system is the presence of a unique type of stem cell that can differentiate into all cell types found in the organism, including the germ line. This represents a simple, extremely powerful, and accessible stem cell system in which to address a variety of important questions. In the last ten years, molecular, cellular, and bioinformatics tools have been established for use in this model, making it ideally placed for in vivo analysis of stem cells in their natural environment without ethical complications.

  15. [Stem cells: limitations and opportunities in Peru].

    PubMed

    Amiel-Pérez, José; Casado, Fanny

    2015-10-01

    Stem cells are defined as rare cells that are characterized by asymmetric division, a process known as self-renewal, and the potential to differentiate into more than one type of terminally differentiated cell. There is a diversity of stem cells including embryonic stem cells, which exist only during the first stages of human development, and many adult stem cells depending on the specific tissues from where they derive or the ones derived from mesenchymal or stromal tissues. On the other hand, there are induced pluripotent stem cells generated by genetic engineering with similar properties to embryonic stem cells that are derived from adult tissues without the ethical and legal limitations. In all cases, there are many questions that are being addressed by research in basic sciences to better inform clinical practice. In Peru, there is much to do refining techniques and improving methodologies, which requires experience, proper facilities and highly specialized human resources. However, there are interesting efforts to place Peruvian stem cell research in the international scientific arena.

  16. Cardiac stem cell aging and heart failure.

    PubMed

    Cesselli, Daniela; Aleksova, Aneta; Mazzega, Elisa; Caragnano, Angela; Beltrami, Antonio Paolo

    2017-01-19

    A side effect of the medical improvements of the last centuries is the progressive aging of the world population, which is estimated to reach the impressive number of 2 billion people with more than 65 years by 2050. As a consequence, age-related diseases, such as heart failure, will affect more and more patients in the next years. To understand the biological bases of these diseases will be a crucial task in order to find better treatments, and possibly slow age-related morbidity and mortality. Cardiac stem cells have been at the center of a heated debate and their potential involvement in cardiac homeostasis has been questioned. In this review, we summarize evidence obtained by independent groups, on different animal models and humans, that strongly support the important role played by immature, cardiac resident cells in the cardioprotection against heart failure.

  17. [Post-hematopietic stem cell transplant complications].

    PubMed

    de Berranger, Eva; Jubert, Charlotte; Michel, Gérard

    2015-01-01

    Under the long-term monitoring of patients treated in childhood or adolescence for cancer, we present in this article the long-term monitoring and therefore possible effects of patients who underwent allergenic hematopoietic stem cell transplantation. This article is based on a collaborative effort organized by the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which took place during the 4th day of allograft harmonization practices. Patients affected are children and young adults (0-25 years). We defined the monitoring effects beyond 1 year post-transplant. Our recommendations are based on a literature review, in line with the Leucémie Enfant Adulte (LEA) study cohort of long-term monitoring of patients treated for hematological malignancies in childhood, grafted or not. It became important to determine the nature of problems, their risk factors, frequency and monitoring necessary to implement for their detection. We will not address the therapeutic management of sequelae.

  18. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    PubMed

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  19. PLURIPOTENT STEM CELL APPLICATIONS FOR REGENERATIVE MEDICINE

    PubMed Central

    Angelos, Mathew G.; Kaufman, Dan S.

    2015-01-01

    Purpose of Review In this review, we summarize the current status of clinical trials using therapeutic cells produced from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We also discuss combined cell and gene therapy via correction of defined mutations in human pluripotent stem cells and provide commentary on key obstacles facing wide-scale clinical adoption of pluripotent stem cell-based therapy. Recent Findings Initial data suggest hESC/hiPSC-derived cell products used for retinal repair and spinal cord injury are safe for human use. Early stage studies for treatment of cardiac injury and diabetes are also in progress. However, there remain key concerns regarding the safety and efficacy of these cells that need to be addressed in additional well-designed clinical trials. Advances using the CRISPR/Cas9 gene-editing system offer an improved tool for more rapid and on-target gene correction of genetic diseases. Combined gene and cell therapy using human pluripotent stem cells may provide an additional curative approach for disabling or lethal genetic and degenerative diseases where there are currently limited therapeutic opportunities. Summary Human pluripotent stem cells are emerging as a promising tool to produce cells and tissues suitable for regenerative therapy for a variety of genetic and degenerative diseases. PMID:26536430

  20. Stem cells in pediatric heart failure.

    PubMed

    Pillekamp, F; Khalil, M; Emmel, M; Brockmeier, K; Hescheler, J

    2008-06-01

    Pediatric heart failure could be a target for regenerative therapy. Stem cell-based therapy has the potential to provide functional cardiomyocytes. Whereas adult stem cells have shown no or only minimal therapeutic benefit in adults with no evidence of transdifferentiation, embryonic stem cells can differentiate to any cell type, including cardiomyocytes. However, ethical concerns and immunological problems are associated with embryonic stem cells derived from the inner cell mass of blastocysts. Recently, somatic cells could be reprogrammed to a pluripotent state (i.e. induced pluripotent stem cells) with the help of transcription factors. This technique removes ethical and probably also immunological concerns. Nevertheless extensive experimental research will be necessary before cell replacement strategies become clinically applicable. Because the underlying pathophysiology differs significantly with age, caution is warranted extrapolating data obtained in experimental models of cardiac ischemia and clinical studies in adults to the pediatric population. Pediatric heart failure has a good prognosis if causal therapy is possible. However, some forms of congenital heart disease and especially dilated cardiomyopathy still have limited therapeutic options. Almost half of children with symptomatic cardiomyopathy receive a transplant or die within two years. The authors will review the relevant stem cell sources for cell-based treatments. And, given the differences of the underlying diseases between adult and pediatric patients with heart failure, it is contemplated which condition of pediatric patients with heart failure is most likely to benefit and which cell type would be appropriate.

  1. Signal propagation in stem-cell niches

    NASA Astrophysics Data System (ADS)

    Zhdanov, Vladimir P.

    2009-09-01

    Stem cells, maintaining tissue homeostasis, are nurtured in microscopic niches formed of so-called environmental cells. The kinetics of proliferation and differentiation of stem cells in such niches depend on their interaction with the messenger proteins secreted by environmental cells. We propose a generic mean-field kinetic model of the propagation of such signals. To motivate our study, we briefly describe a stem-cell niche in the Drosophila ovary. Our model is however applicable to other niches as well. In particular, it helps one to understand the necessary conditions for the niche function. For example, the model predicts that in the case of the Drosophila ovary each germline stem cell should have in the external membrane at least 700 receptors interacting with the signaling Dpp and Gpp proteins emanating from the cap cells.

  2. Multipotent Stem Cells in Cardiac Regeneration

    PubMed Central

    Karra, Ravi; Wu, Sean M.

    2008-01-01

    Summary The potential for stem cells to ameliorate or cure heart diseases has galvanized a cadre of cardiovascular translational and clinical scientists to take a “first-in-man” approach using autologous stem cells from a variety of tissues. However, recent clinical trial data show that when these cells are given by intracoronary infusion or direct myocardial injection, limited improvement in heart function occurs with no evidence of cardiomyogenesis. These studies illustrate the great need to understand the logic of cell-lineage commitment and the principles of cardiac differentiation. Recent identification of stem/progenitor cells of embryological origin with intrinsic competence to differentiate into multiple lineages within the heart offers new possibilities for cardiac regeneration. When combined with developments in nuclear reprogramming and provided that tumor risks and other challenges of embryonic cell transplantation can be overcome, the prospect of achieving autologous, cardiomyogenic, stem cell-based therapy may be within reach. PMID:18307403

  3. Odontogenic epithelial stem cells: hidden sources.

    PubMed

    Padma Priya, Sivan; Higuchi, Akon; Abu Fanas, Salem; Pooi Ling, Mok; Kumari Neela, Vasantha; Sunil, P M; Saraswathi, T R; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh

    2015-12-01

    The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed.

  4. Stem cells in toxicology: fundamental biology and practical considerations.

    PubMed

    Kang, Kyung-Sun; Trosko, James E

    2011-03-01

    This "Commentary" has examined the use of human stem cells for detection of toxicities of physical, chemical, and biological toxins/toxicants in response to the challenge posed by the NRC Report, "Toxicity Testing in the 21st Century: A vision and Strategy." Before widespread application of the use of human embryonic, pluripotent, "iPS," or adult stem cells be considered, the basic characterization of stem cell biology should be undertaken. Because no in vitro system can mimic all factors that influence cells in vivo (individual genetic, gender, developmental, immunological and diurnal states; niche conditions; complex intercellular interactions between stem, progenitor, terminal differentiated cells, and the signaling from extracellular matrices, oxygen tensions, etc.), attempts should be made to use both embryonic and adult stem cells, grown in three dimension under "niche-like" conditions. Because many toxins and toxicants work by "epigenetic" mechanisms and that epigenetic mechanisms play important roles in regulating gene expression and in the pathogenesis of many human diseases, epigenetic toxicity must be incorporated in toxicity testing. Because modulation of gap junctional intercellular communication by epigenetic agents plays a major role in homeostatic regulation of both stem and progenitor cells in normal tissues, the modulation of this biological process by both endogenous and endogenous chemicals should be incorporated as an end point to monitor for potential toxicities or chemo-preventive attributes. In addition, modulation of quantity, as well as the quality, of stem cells should be considered as potential source of a chemical's toxic potential in affecting any stem cell-based pathology, such as cancer.

  5. [Hematopoietic stem cell transplantation in autoimmune diseases].

    PubMed

    Albarracín, Flavio; López Meiller, María José; Naswetter, Gustavo; Longoni, Héctor

    2008-01-01

    Transplantation of hematopoietic stem cells, which are capable of self renewal and reconstitution of all types of blood cells, can be a treatment for numerous potential lethal diseases, including leukemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant multiple sclerosis, lupus and systemic sclerosis. Studies in animal models show that the transfer of hematopoietic stem cells can reverse autoimmunity. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.

  6. Update on small intestinal stem cells.

    PubMed

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-08-07

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

  7. A Comparative Transcriptomic Analysis Reveals Conserved Features of Stem Cell Pluripotency in Planarians and Mammals

    PubMed Central

    Labbé, Roselyne M.; Irimia, Manuel; Currie, Ko W.; Lin, Alexander; Zhu, Shu Jun; Brown, David D.R.; Ross, Eric J.; Voisin, Veronique; Bader, Gary D.; Blencowe, Benjamin J.; Pearson, Bret J.

    2014-01-01

    Many long-lived species of animals require the function of adult stem cells throughout their lives. However, the transcriptomes of stem cells in invertebrates and vertebrates have not been compared, and consequently, ancestral regulatory circuits that control stem cell populations remain poorly defined. In this study, we have used data from high-throughput RNA sequencing to compare the transcriptomes of pluripotent adult stem cells from planarians with the transcriptomes of human and mouse pluripotent embryonic stem cells. From a stringently defined set of 4,432 orthologs shared between planarians, mice and humans, we identified 123 conserved genes that are ≥5-fold differentially expressed in stem cells from all three species. Guided by this gene set, we used RNAi screening in adult planarians to discover novel stem cell regulators, which we found to affect the stem cell-associated functions of tissue homeostasis, regeneration, and stem cell maintenance. Examples of genes that disrupted these processes included the orthologs of TBL3, PSD12, TTC27, and RACK1. From these analyses, we concluded that by comparing stem cell transcriptomes from diverse species, it is possible to uncover conserved factors that function in stem cell biology. These results provide insights into which genes comprised the ancestral circuitry underlying the control of stem cell self-renewal and pluripotency. PMID:22696458

  8. A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals.

    PubMed

    Labbé, Roselyne M; Irimia, Manuel; Currie, Ko W; Lin, Alexander; Zhu, Shu Jun; Brown, David D R; Ross, Eric J; Voisin, Veronique; Bader, Gary D; Blencowe, Benjamin J; Pearson, Bret J

    2012-08-01

    Many long-lived species of animals require the function of adult stem cells throughout their lives. However, the transcriptomes of stem cells in invertebrates and vertebrates have not been compared, and consequently, ancestral regulatory circuits that control stem cell populations remain poorly defined. In this study, we have used data from high-throughput RNA sequencing to compare the transcriptomes of pluripotent adult stem cells from planarians with the transcriptomes of human and mouse pluripotent embryonic stem cells. From a stringently defined set of 4,432 orthologs shared between planarians, mice and humans, we identified 123 conserved genes that are ≥5-fold differentially expressed in stem cells from all three species. Guided by this gene set, we used RNAi screening in adult planarians to discover novel stem cell regulators, which we found to affect the stem cell-associated functions of tissue homeostasis, regeneration, and stem cell maintenance. Examples of genes that disrupted these processes included the orthologs of TBL3, PSD12, TTC27, and RACK1. From these analyses, we concluded that by comparing stem cell transcriptomes from diverse species, it is possible to uncover conserved factors that function in stem cell biology. These results provide insights into which genes comprised the ancestral circuitry underlying the control of stem cell self-renewal and pluripotency.

  9. Stem cell tracking using iron oxide nanoparticles.

    PubMed

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

    2014-01-01

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

  10. Time to reconsider stem cell induction strategies.

    PubMed

    Denker, Hans-Werner

    2012-12-17

    Recent developments in stem cell research suggest that it may be time to reconsider the current focus of stem cell induction strategies. During the previous five years, approximately, the induction of pluripotency in somatic cells, i.e., the generation of so-called 'induced pluripotent stem cells' (iPSCs), has become the focus of ongoing research in many stem cell laboratories, because this technology promises to overcome limitations (both technical and ethical) seen in the production and use of embryonic stem cells (ESCs). A rapidly increasing number of publications suggest, however, that it is now possible to choose instead other, alternative ways of generating stem and progenitor cells bypassing pluripotency. These new strategies may offer important advantages with respect to ethics, as well as to safety considerations. The present communication discusses why these strategies may provide possibilities for an escape from the dilemma presented by pluripotent stem cells (self-organization potential, cloning by tetraploid complementation, patenting problems and tumor formation risk).

  11. Current understanding concerning intestinal stem cells

    PubMed Central

    Cui, Shuang; Chang, Peng-Yu

    2016-01-01

    In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same. PMID:27610020

  12. Potential use of stem cells in neuroreplacement therapies for neurodegenerative diseases.

    PubMed

    Sugaya, Kiminobu

    2003-01-01

    The use of stem cells for neuroreplacement therapy is no longer science fiction--it is science fact. We have succeeded in the development of neural and mesenchymal stem cell transplantation to produce neural cells in the brain. We have also seen improvement in cognitive function following stem cell transplantation in a memory-impaired aged animal model. These results promise a bright future for stem cell therapies in neurodegenerative diseases. Before we begin to think about clinical applications beyond the present preclinical studies, we have to consider the pathophysiological environment of individual diseases and weigh the factors that affect stem cell biology. Here, I not only review potential therapeutic applications of stem cell strategies in neurodegenerative diseases, but also discuss stem cell biology regarding factors that are altered under disease conditions.

  13. Current stem cell based therapies in diabetes

    PubMed Central

    Lilly, Meredith A; Davis, Meghan F; Fabie, Josh E; Terhune, Elizabeth B; Gallicano, G Ian

    2016-01-01

    Diabetes is a disease with wide-ranging personal and societal impacts that has been managed medicinally for over half a century. Since the discovery of stem cells, pancreatic islet regeneration has become a central target for clinical application that has the potential to decrease or eliminate the need for insulin administration and adjunctive medications. The discovery of alternative routes to pluripotency that bypass the ethical implications of embryonic stem cells has significantly expanded the horizons of stem cell based therapy. Engraftment of mature insulin producing cells derived from induced pluripotent stem cells may represent the most promising treatment strategy for diabetic patients with impaired β-cell function. These cells are easily accessible and have been shown to closely mimic endogenous β-cell function in vivo. While the risks of oncogenesis and transplant rejection are still of great concern, large strides have been made on both fronts with the application of integration free induction strategies and the ongoing development of microcapsules that cloak implanted cells from an autoimmune response. This review will focus on the progress and remaining obstacles in diabetes related stem cell research, and will specifically discuss approaches using embryonic, induced pluripotent, germline and mesenchymal derived stem cells. PMID:27853630

  14. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed.

  15. Cellular quiescence in mammary stem cells and breast tumor stem cells: got testable hypotheses?

    PubMed

    Harmes, David C; DiRenzo, James

    2009-03-01

    Cellular quiescence is a state of reversible cell cycle arrest and has more recently been shown to be a blockade to differentiation and to correlate with resistance to cancer chemotherapeutics and other xenobiotics; features that are common to adult stem cells and possibly tumor stem cells. The biphasic kinetics of mammary regeneration, coupled to its cyclic endocrine control suggest that mammary stem cells most likely divide during a narrow window of the regenerative cycle and return to a state of quiescence. This would enable them to retain their proliferative capacity, resist differentiation signals and preserve their prolonged life span. There is accumulating evidence that mammary stem cells and other adult stem cells utilize quiescence for this purpose, however the degree to which tumor stem cells do so is largely unknown. The retained proliferative capacity of mammary stem cells likely enables them to accumulate and harbor mutations that lead to breast cancer initiation. However it is currently unclear if these causative lesions lead to defective or deranged quiescence in mammary stem cells. Evidence of such effects could potentially lead to the development of diagnostic systems that monitor mammary stem cell quiescence or activation. Such systems may be useful for the evaluation of patients who are at significant risk of breast cancer. Additionally quiescence has been postulated to contribute to therapeutic resistance and tumor recurrence. This review aims to evaluate what is known about the mechanisms governing cellular quiescence and the role of tumor stem cell quiescence in breast cancer recurrence.

  16. Engineering nanoscale stem cell niche: direct stem cell behavior at cell-matrix interface.

    PubMed

    Zhang, Yan; Gordon, Andrew; Qian, Weiyi; Chen, Weiqiang

    2015-09-16

    Biophysical cues on the extracellular matrix (ECM) have proven to be significant regulators of stem cell behavior and evolution. Understanding the interplay of these cells and their extracellular microenvironment is critical to future tissue engineering and regenerative medicine, both of which require a means of controlled differentiation. Research suggests that nanotopography, which mimics the local, nanoscale, topographic cues within the stem cell niche, could be a way to achieve large-scale proliferation and control of stem cells in vitro. This Progress Report reviews the history and contemporary advancements of this technology, and pays special attention to nanotopographic fabrication methods and the effect of different nanoscale patterns on stem cell response. Finally, it outlines potential intracellular mechanisms behind this response.

  17. ETOPOSIDE INDUCES CHROMOSOMAL ABNORMALITIES IN SPERMATOCYTES AND SPERMATOGONIAL STEM CELLS

    SciTech Connect

    Marchetti, F; Pearson, F S; Bishop, J B; Wyrobek, A J

    2005-07-15

    Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukemia, lymphomas and many solid tumors, such as testicular and ovarian cancers, that affect patients in their reproductive years. The purpose of the study was to use sperm FISH analyses to characterize the long-term effects of ET on male germ cells. We used a mouse model to characterize the induction of chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. ET treatment resulted in major increases in the frequencies of sperm carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. These results demonstrate that male meiotic germ cells are considerably more sensitive to ET than spermatogonial stem-cell and that increased frequencies of sperm with structural aberrations persist after spermatogonial stem-cell treatment. These findings predict that patients who undergo chemotherapy with ET may have transient elevations in the frequencies of aneuploid sperm, but more importantly, may have persistent elevations in the frequencies of sperm with chromosomal aberrations, placing them at higher risk for abnormal reproductive outcomes long after the end of their chemotherapy.

  18. O-Linked N-Acetylglucosamine (O-GlcNAc) Expression Levels Epigenetically Regulate Colon Cancer Tumorigenesis by Affecting the Cancer Stem Cell Compartment via Modulating Expression of Transcriptional Factor MYBL1.

    PubMed

    Guo, Huabei; Zhang, Bing; Nairn, Alison V; Nagy, Tamas; Moremen, Kelley W; Buckhaults, Phillip; Pierce, Michael

    2017-03-10

    To study the regulation of colorectal adenocarcinoma progression by O-GlcNAc, we have focused on the O-GlcNAc-mediated epigenetic regulation of human colon cancer stem cells (CCSC). Xenograft tumors from colon tumor cells with O-linked N-acetylglucosamine transferase (OGT) knockdown grew significantly slower than those formed from control cells, indicating a reduced proliferation of tumor cells due to inhibition of OGT expression. Significant reduction of the CCSC population was observed in the tumor cells after OGT knockdown, whereas tumor cells treated with the O-GlcNAcase inhibitor showed an increased CCSC population, indicating that O-GlcNAc levels regulated the CCSC compartment. When grown in suspension, tumor cells with OGT knockdown showed a reduced ability to form tumorspheres, indicating a reduced self-renewal of CCSC due to reduced levels of O-GlcNAc. ChIP-sequencing experiments using an anti-O-GlcNAc antibody revealed significant chromatin enrichment of O-GlcNAc-modified proteins at the promoter of the transcription factor MYBL1, which was also characterized by the presence of H3K27me3. RNA-sequencing analysis showed an increased expression of MYBL1 in tumor cells with OGT knockdown. Forced overexpression of MYBL1 led to a reduced population of CCSC and tumor growth in vivo, similar to the effects of OGT silencing. Moreover, two CpG islands near the transcription start site of MYBL1 were identified, and O-GlcNAc levels regulated their methylation status. These results strongly argue that O-GlcNAc epigenetically regulates MYBL1, functioning similarly to H3K27me3. The aberrant CCSC compartment observed after modulating O-GlcNAc levels is therefore likely to result, at least in part, from the epigenetic regulation of MYBL1 expression by O-GlcNAc, thereby significantly affecting tumor progression.

  19. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    PubMed

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  20. Induced pluripotent stem (iPS) cells from human fetal stem cells.

    PubMed

    Guillot, Pascale V

    2016-02-01

    Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications.

  1. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    DTIC Science & Technology

    2015-07-01

    AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM ELEMENT NUMBER 6...some oncogene function in determining molecular phenotypes. To test this hypothesis, we proposed to transform neural stem cells (NSCs) and neural

  2. Minireview: Nuclear Receptors, Hematopoiesis, and Stem Cells

    PubMed Central

    Chute, John P.; Ross, Joel R.; McDonnell, Donald P.

    2010-01-01

    Nuclear receptors (NRs) regulate a panoply of biological processes, including the function and development of cells within the hematopoietic and immune system, such as erythrocytes, monocytes, and lymphocytes. Significantly less is known regarding the function of NRs in regulating the fate of hematopoietic stem cells (HSCs), the self-renewing, pluripotent cells that give rise to the entirety of the blood and immune systems throughout the lifetime of an individual. Several recent studies suggest, either directly or indirectly, a role for members of the NR family in regulating the differentiation and self-renewal of HSCs, embryonic stem cells, and induced pluripotent stem cells. Herein, we review in detail the function of specific NRs in controlling HSC and other stem cell fate and propose a framework through which these observations can be translated into therapeutic amplification of HSCs for clinical purposes. PMID:19934345

  3. Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development

    PubMed Central

    Frodermann, Vanessa; van Duijn, Janine; van Pel, Melissa; van Santbrink, Peter J.; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C. A.

    2015-01-01

    Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into low-density lipoprotein-receptor knockout mice and put these on a Western-type diet to induce atherosclerosis. Initially after treatment, we found higher levels of circulating regulatory T cells. In the long-term, overall numbers of effector T cells were reduced by MSC treatment. Moreover, MSC-treated mice displayed a significant 33% reduction in circulating monocytes and a 77% reduction of serum CCL2 levels. Most strikingly, we found a previously unappreciated effect on lipid metabolism. Serum cholesterol was reduced by 33%, due to reduced very low-density lipoprotein levels, likely a result of reduced de novo hepatic lipogenesis as determined by a reduced expression of Stearoyl-CoA desaturase-1 and lipoprotein lipase. MSCs significantly affected lesion development, which was reduced by 33% in the aortic root. These lesions contained 56% less macrophages and showed a 61% reduction in T cell numbers. We show here for the first time that MSC treatment affects not only inflammatory responses but also significantly reduces dyslipidaemia in mice. This makes MSCs a potent candidate for atherosclerosis therapies. PMID:26490642

  4. Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche.

    PubMed

    Rhiner, Christa; Díaz, Begoña; Portela, Marta; Poyatos, Juan F; Fernández-Ruiz, Irene; López-Gay, Jesús M; Gerlitz, Offer; Moreno, Eduardo

    2009-03-01

    Cell competition is a short-range cell-cell interaction leading to the proliferation of winner cells at the expense of losers, although either cell type shows normal growth in homotypic environments. Drosophila Myc (dMyc; Dm-FlyBase) is a potent inducer of cell competition in wing epithelia, but its role in the ovary germline stem cell niche is unknown. Here, we show that germline stem cells (GSCs) with relative lower levels of dMyc are replaced by GSCs with higher levels of dMyc. By contrast, dMyc-overexpressing GSCs outcompete wild-type stem cells without affecting total stem cell numbers. We also provide evidence for a naturally occurring cell competition border formed by high dMyc-expressing stem cells and low dMyc-expressing progeny, which may facilitate the concentration of the niche-provided self-renewal factor BMP/Dpp in metabolically active high dMyc stem cells. Genetic manipulations that impose uniform dMyc levels across the germline produce an extended Dpp signaling domain and cause uncoordinated differentiation events. We propose that dMyc-induced competition plays a dual role in regulating optimal stem cell pools and sharp differentiation boundaries, but is potentially harmful in the case of emerging dmyc duplications that facilitate niche occupancy by pre-cancerous stem cells. Moreover, competitive interactions among stem cells may be relevant for the successful application of stem cell therapies in humans.

  5. Analytical strategies for studying stem cell metabolism

    PubMed Central

    Arnold, James M.; Choi, William T.; Sreekumar, Arun

    2015-01-01

    Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology. PMID:26213533

  6. Analytical strategies for studying stem cell metabolism.

    PubMed

    Arnold, James M; Choi, William T; Sreekumar, Arun; Maletić-Savatić, Mirjana

    2015-04-01

    Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology.

  7. Time to Reconsider Stem Cell Induction Strategies

    PubMed Central

    Denker, Hans-Werner

    2012-01-01

    Recent developments in stem cell research suggest that it may be time to reconsider the current focus of stem cell induction strategies. During the previous five years, approximately, the induction of pluripotency in somatic cells, i.e., the generation of so-called ‘induced pluripotent stem cells’ (iPSCs), has become the focus of ongoing research in many stem cell laboratories, because this technology promises to overcome limitations (both technical and ethical) seen in the production and use of embryonic stem cells (ESCs). A rapidly increasing number of publications suggest, however, that it is now possible to choose instead other, alternative ways of generating stem and progenitor cells bypassing pluripotency. These new strategies may offer important advantages with respect to ethics, as well as to safety considerations. The present communication discusses why these strategies may provide possibilities for an escape from the dilemma presented by pluripotent stem cells (self-organization potential, cloning by tetraploid complementation, patenting problems and tumor formation risk). PMID:24710555

  8. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

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

  9. Fibronectin and stem cell differentiation – lessons from chondrogenesis

    PubMed Central

    Singh, Purva; Schwarzbauer, Jean E.

    2012-01-01

    Summary The extracellular matrix (ECM) is an intricate network of proteins that surrounds cells and has a central role in establishing an environment that is conducive to tissue-specific cell functions. In the case of stem cells, this environment is the stem cell niche, where ECM signals participate in cell fate decisions. In this Commentary, we describe how changes in ECM composition and mechanical properties can affect cell shape and stem cell differentiation. Using chondrogenic differentiation as a model, we examine the changes in the ECM that occur before and during mesenchymal stem cell differentiation. In particular, we focus on the main ECM protein fibronectin, its temporal expression pattern during chondrogenic differentiation, its potential effects on functions of differentiating chondrocytes, and how its interactions with other ECM components might affect cartilage development. Finally, we discuss data that support the possibility that the fibronectin matrix has an instructive role in directing cells through the condensation, proliferation and/or differentiation stages of cartilage formation. PMID:22976308

  10. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups.

    PubMed

    Randolph, Matthew E; Pavlath, Grace K

    2015-01-01

    The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease.

  11. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

    PubMed Central

    Randolph, Matthew E.; Pavlath, Grace K.

    2015-01-01

    The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease. PMID:26500547

  12. Determination of telomerase activity in stem cells and non-stem cells of breast cancer.

    PubMed

    Li, Zhi; He, Yanli; Zhang, Jiahua; Zhang, Jinghui; Huang, Tao

    2007-07-01

    Although all normal tissue cells, including stem cells, are genetically homologous, variation in gene expression patterns has already determined the distinct roles for individual cells in the physiological process due to the occurrence of epigenetic modification. This is of special importance for the existence of tissue stem cells because they are exclusively immortal within the body, capable of self-replicating and differentiating by which tissues renew and repair itself and the total tissue cell population maintains a steady-state. Impairment of tissue stem cells is usually accompanied by a reduction in cell number, slows down the repair process and causes hypofunction. For instance, chemotherapy usually leads to depression of bone marrow and hair loss. Cellular aging is closely associated with the continuous erosion of the telomere while activation of telomerase repairs and maintains telomeres, thus slowing the aging process and prolonging cell life. In normal adults, telomerase activation mainly presents in tissue stem cells and progenitor cells giving them unlimited growth potential. Despite the extensive demonstration of telomerase activation in malignancy (> 80%), scientists found that heterogeneity also exists among the tumor cells and only minorities of cells, designated as cancer stem cells, undergo processes analogous to the self-renewal and differentiation of normal stem cells while the rest have limited lifespans. In this study, telomerase activity was measured and compared in breast cancer stem cells and non-stem cells that were phenotypically sorted by examining surface marker expression. The results indicated that cancer stem cells show a higher level of enzyme activity than non-stem cells. In addition, associated with the repair of cancer tissue (or relapse) after chemotherapy, telomerase activity in stem cells was markedly increased.

  13. Cancer stem cells, cancer cell plasticity and radiation therapy.

    PubMed

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.

  14. Stem cells engineering for cell-based therapy.

    PubMed

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  15. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    NASA Astrophysics Data System (ADS)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  16. Cancer stem cells and differentiation therapy.

    PubMed

    Sell, Stewart

    2006-01-01

    Cancers arise from stem cells in adult tissues and the cells that make up a cancer reflect the same stem cell --> progeny --> differentiation progression observed in normal tissues. All adult tissues are made up of lineages of cells consisting of tissue stem cells and their progeny (transit-amplifying cells and terminally differentiated cells); the number of new cells produced in normal tissue lineages roughly equals the number of old cells that die. Cancers result from maturation arrest of this process, resulting in continued proliferation of cells and a failure to differentiate and die. The biological behavior, morphological appearance, and clinical course of a cancer depend on the stage of maturation at which the genetic lesion is activated. This review makes a comparison of cancer cells to embryonic stem cells and to adult tis sue stem cells while addressing two basic questions: (1) Where do cancers come from?, and (2) How do cancers grow? The answers to these questions are critical to the development of approaches to the detection, prevention, and treatment of cancer.

  17. The CSF-1 receptor fashions the intestinal stem cell niche.

    PubMed

    Akcora, Dilara; Huynh, Duy; Lightowler, Sally; Germann, Markus; Robine, Sylvie; de May, Jan R; Pollard, Jeffrey W; Stanley, E Richard; Malaterre, Jordane; Ramsay, Robert G

    2013-03-01

    Gastrointestinal (GI) homeostasis requires the action of multiple pathways. There is some controversy regarding whether small intestine (SI) Paneth cells (PCs) play a central role in orchestrating crypt architecture and their relationship with Lgr5+ve stem cells. Nevertheless, we previously showed that germline CSF-1 receptor (Csf1r) knock out (KO) or Csf1 mutation is associated with an absence of mature PC, reduced crypt proliferation and lowered stem cell gene, Lgr5 expression. Here we show the additional loss of CD24, Bmi1 and Olfm4 expression in the KO crypts and a high resolution 3D localization of CSF-1R mainly to PC. The induction of GI-specific Csf1r deletion in young adult mice also led to PC loss over a period of weeks, in accord with the anticipated long life span of PC, changed distribution of proliferating cells and this was with a commensurate loss of Lgr5 and other stem cell marker gene expression. By culturing SI organoids, we further show that the Csf1r(-/-) defect in PC production is intrinsic to epithelial cells as well as definitively affecting stem cell activity. These results show that CSF-1R directly supports PC maturation and that in turn PCs fashion the intestinal stem cell niche.

  18. Stem Cells in Skin Wound Healing: Are We There Yet?

    PubMed Central

    Cerqueira, Mariana Teixeira; Pirraco, Rogério Pedro; Marques, Alexandra Pinto

    2016-01-01

    Significance: Cutaneous wound healing is a serious problem worldwide that affects patients with various wound types, resulting from burns, traumatic injuries, and diabetes. Despite the wide range of clinically available skin substitutes and the different therapeutic alternatives, delayed healing and scarring are often observed. Recent Advances: Stem cells have arisen as powerful tools to improve skin wound healing, due to features such as effective secretome, self-renewal, low immunogenicity, and differentiation capacity. They represent potentially readily available biological material that can particularly target distinct wound-healing phases. In this context, mesenchymal stem cells have been shown to promote cell migration, angiogenesis, and a possible regenerative rather than fibrotic microenvironment at the wound site, mainly through paracrine signaling with the surrounding cells/tissues. Critical Issues: Despite the current insights, there are still major hurdles to be overcome to achieve effective therapeutic effects. Limited engraftment and survival at the wound site are still major concerns, and alternative approaches to maximize stem cell potential are a major demand. Future Directions: This review emphasizes two main strategies that have been explored in this context. These comprise the exploration of hypoxic conditions to modulate stem cell secretome, and the use of adipose tissue stromal vascular fraction as a source of multiple cells, including stem cells and factors requiring minimal manipulation. Nonetheless, the attainment of these approaches to target successfully skin regeneration will be only evident after a significant number of in vivo works in relevant pre-clinical models. PMID:27076994

  19. Evidence for Human Lung Stem Cells

    PubMed Central

    Kajstura, Jan; Rota, Marcello; Hall, Sean R.; Hosoda, Toru; D’Amario, Domenico; Sanada, Fumihiro; Zheng, Hanqiao; Ogórek, Barbara; Rondon-Clavo, Carlos; Ferreira-Martins, João; Matsuda, Alex; Arranto, Christian; Goichberg, Polina; Giordano, Giovanna; Haley, Kathleen J.; Bardelli, Silvana; Rayatzadeh, Hussein; Liu, Xiaoli; Quaini, Federico; Liao, Ronglih; Leri, Annarosa; Perrella, Mark A.; Loscalzo, Joseph; Anversa, Piero

    2011-01-01

    BACKGROUND Although progenitor cells have been described in distinct anatomical regions of the lung, description of resident stem cells has remained elusive. METHODS Surgical lung-tissue specimens were studied in situ to identify and characterize human lung stem cells. We defined their phenotype and functional properties in vitro and in vivo. RESULTS Human lungs contain undifferentiated human lung stem cells nested in niches in the distal airways. These cells are self-renewing, clonogenic, and multipotent in vitro. After injection into damaged mouse lung in vivo, human lung stem cells form human bronchioles, alveoli, and pulmonary vessels integrated structurally and functionally with the damaged organ. The formation of a chimeric lung was confirmed by detection of human transcripts for epithelial and vascular genes. In addition, the self-renewal and long-term proliferation of human lung stem cells was shown in serial-transplantation assays. CONCLUSIONS Human lungs contain identifiable stem cells. In animal models, these cells participate in tissue homeostasis and regeneration. They have the undemonstrated potential to promote tissue restoration in patients with lung disease. (Funded by the National Institutes of Health.) PMID:21561345

  20. Growing vascularized heart tissue from stem cells.

    PubMed

    Lim, Shiang Y; Hernández, Damián; Dusting, Gregory J

    2013-08-01

    The promise of stem cells to repair the heart after damage or heart attack has not been realized because most such cells are lost after transplantation. A new approach is to grow substantial viable pieces of cardiac tissue from human stem cells by cardiac tissue engineering. Such constructs must be fully vascularized and perfused to ensure the viability of clinically relevant volumes of tissue. This requires careful choice of cells, culture conditions, a biomaterial to act as scaffold, and crucial strategies for vascularization. Autologous stem cells with high plasticity, which would avoid the need for antirejection therapies after transplantation, are an attractive source of both cardiomyocytes and vascular cells. Most stem cells also have inherent paracrine activity, releasing cytoprotective factors and growth-promoting cytokines that can further stimulate tissue regeneration and neovascularization through recruitment of endogenous stem and progenitor cells. Current advances for growing vascularized and functional cardiac constructs with human stem cells are described, bringing us a step closer to the engineering of complex cardiac tissues such as pacemaker, conducting tissue, or contractile myocardial flaps ideal for transplantation. From studies in rats successful transplantation of thin constructs to the ventricle has been reported, but there remain further issues to resolve before larger human constructs will be available to test in the clinic.

  1. Preclinical Assessment of Stem Cell Therapies for Neurological Diseases

    PubMed Central

    Joers, Valerie L.; Emborg, Marina E.

    2010-01-01

    Stem cells, as subjects of study for use in treating neurological diseases, are envisioned as a replacement for lost neurons and glia, a means of trophic support, a therapeutic vehicle, and, more recently, a tool for in vitro modeling to understand disease and to screen and personalize treatments. In this review we analyze the requirements of stem cell–based therapy for clinical translation, advances in stem cell research toward clinical application for neurological disorders, and different animal models used for analysis of these potential therapies. We focus on Parkinson’s disease (typically defined by the progressive loss of dopaminergic nigral neurons), stroke (neurodegeneration associated with decreased blood perfusion in the brain), and multiple sclerosis (an autoimmune disorder that generates demyelination, axonal damage, astrocytic scarring, and neurodegeneration in the brain and spinal cord). We chose these disorders for their diversity and the number of people affected by them. An additional important consideration was the availability of multiple animal models in which to test stem cell applications for these diseases. We also discuss the relationship between the limited number of systematic stem cell studies performed in animals, in particular nonhuman primates and the delayed progress in advancing stem cell therapies to clinical success. PMID:20075496

  2. Stem cells as a treatment for chronic liver disease and diabetes.

    PubMed

    Levicar, N; Dimarakis, I; Flores, C; Tracey, J; Gordon, M Y; Habib, N A

    2007-01-01

    Advances in stem cell biology and the discovery of pluripotent stem cells have made the prospect of cell therapy and tissue regeneration a clinical reality. Cell therapies hold great promise to repair, restore, replace or regenerate affected organs and may perform better than any pharmacological or mechanical device. There is an accumulating body of evidence supporting the contribution of adult stem cells, in particular those of bone marrow origin, to liver and pancreatic islet cell regeneration. In this review, we will focus on the cell therapy for the diseased liver and pancreas by adult haematopoietic stem cells, as well as their possible contribution and application to tissue regeneration. Furthermore, recent progress in the generation, culture and targeted differentiation of human haematopoietic stem cells to hepatic and pancreatic lineages will be discussed. We will also explore the possibility that stem cell technology may lead to the development of clinical modalities for human liver disease and diabetes.

  3. Cell therapy for diabetes mellitus: an opportunity for stem cells?

    PubMed

    Soria, B; Bedoya, F J; Tejedo, J R; Hmadcha, A; Ruiz-Salmerón, R; Lim, S; Martin, F

    2008-01-01

    Diabetes is a chronic disease characterized by a deficit in beta cell mass and a failure of glucose homeostasis. Both circumstances result in a variety of severe complications and an overall shortened life expectancy. Thus, diabetes represents an attractive candidate for cell therapy. Reversal of diabetes can be achieved through pancreas and islet transplantation, but shortage of donor organs has prompted an intensive search for alternative sources of beta cells. This achievement has stimulated the search for appropriate stem cell sources. Both embryonic and adult stem cells have been used to generate surrogate beta cells or otherwise restore beta cell functioning. In this regard, several studies have reported the generation of insulin-secreting cells from embryonic and adult stem cells that normalized blood glucose values when transplanted into diabetic animal models. Due to beta cell complexity, insulin-producing cells generated from stem cells do not possess all beta cell attributes. This indicates the need for further development of methods for differentiation and selection of completely functional beta cells. While these problems are overcome, diabetic patients may benefit from therapeutic strategies based on autologous stem cell therapies addressing late diabetic complications. In this article, we discuss the recent progress in the generation of insulin-producing cells from embryonic and adult stem cells, together with the challenges for the clinical use of diabetes stem cell therapy.

  4. Stem Cell Research and Health Education

    PubMed Central

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2009-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the embryonic form. Consequently, there is public confusion over the benefits currently being derived from the use of stem cells and what can potentially be expected from their use in the future. The health educator’s role is to give an unbiased account of the current state of stem cell research. This paper provides the groundwork by discussing the types of cells currently identified, their potential use, and some of the political and ethical pitfalls resulting from such use. PMID:19672471

  5. Cancer stem cells: mirage or reality?

    PubMed

    Gupta, Piyush B; Chaffer, Christine L; Weinberg, Robert A

    2009-09-01

    The similarities and differences between normal tissue stem cells and cancer stem cells (CSCs) have been the source of much contention, with some recent studies calling into question the very existence of CSCs. An examination of the literature indicates, however, that the CSC model rests on firm experimental foundations and that differences in the observed frequencies of CSCs within tumors reflect the various cancer types and hosts used to assay these cells. Studies of stem cells and the differentiation program termed the epithelial-mesenchymal transition (EMT) point to the possible existence of plasticity between stem cells and their more differentiated derivatives. If present, such plasticity would have major implications for the CSC model and for future therapeutic approaches.

  6. Epithelial stem cells and intestinal cancer.

    PubMed

    Tan, Shawna; Barker, Nick

    2015-06-01

    The mammalian intestine is comprised of an epithelial layer that serves multiple functions in order to maintain digestive activity as well as intestinal homeostasis. This epithelial layer contains highly proliferative stem cells which facilitate its characteristic rapid regeneration. How these stem cells contribute to tissue repair and normal homeostasis are actively studied, and while we have a greater understanding of the molecular mechanisms and cellular locations that underlie stem cell regulation in this tissue, much still remains undiscovered. This review describes epithelial stem cells in both intestinal and non-intestinal tissues, as well as the strategies that have been used to further characterize the cells. Through a discussion of the current understanding of intestinal self-renewal and tissue regeneration in response to injury, we focus on how dysregulation of critical signaling pathways results in potentially oncogenic aberrations, and highlight issues that should be addressed in order for effective intestinal cancer therapies to be devised.

  7. Human embryonic stem cells and lung regeneration.

    PubMed

    Varanou, A; Page, C P; Minger, S L

    2008-10-01

    Human embryonic stem cells are pluripotent cells derived from the inner cell mass of preimplantation stage embryos. Their unique potential to give rise to all differentiated cell types has generated great interest in stem cell research and the potential that it may have in developmental biology, medicine and pharmacology. The main focus of stem cell research has been on cell therapy for pathological conditions with no current methods of treatment, such as neurodegenerative diseases, cardiac pathology, retinal dysfunction and lung and liver disease. The overall aim is to develop methods of application either of pure cell populations or of whole tissue parts to the diseased organ under investigation. In the field of pulmonary research, studies using human embryonic stem cells have succeeded in generating enriched cultures of type II pneumocytes in vitro. On account of their potential of indefinite proliferation in vitro, embryonic stem cells could be a source of an unlimited supply of cells available for transplantation and for use in gene therapy. Uncovering the ability to generate such cell types will expand our understanding of biological processes to such a degree that disease understanding and management could change dramatically.

  8. On the stem cell origin of cancer.

    PubMed

    Sell, Stewart

    2010-06-01

    In each major theory of the origin of cancer-field theory, chemical carcinogenesis, infection, mutation, or epigenetic change-the tissue stem cell is involved in the generation of cancer. Although the cancer type is identified by the more highly differentiated cells in the cancer cell lineage or hierarchy (transit-amplifying cells), the property of malignancy and the molecular lesion of the cancer exist in the cancer stem cell. In the case of teratocarcinomas, normal germinal stem cells have the potential to become cancers if placed in an environment that allows expression of the cancer phenotype (field theory). In cancers due to chemically induced mutations, viral infections, somatic and inherited mutations, or epigenetic changes, the molecular lesion or infection usually first occurs in the tissue stem cells. Cancer stem cells then give rise to transit-amplifying cells and terminally differentiated cells, similar to what happens in normal tissue renewal. However, the major difference between cancer growth and normal tissue renewal is that whereas normal transit amplifying cells usually differentiate and die, at various levels of differentiation, the cancer transit-amplifying cells fail to differentiate normally and instead accumulate (ie, they undergo maturation arrest), resulting in cancer growth.

  9. Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells.

    PubMed

    Yamada, Mitsutoshi; Johannesson, Bjarki; Sagi, Ido; Burnett, Lisa Cole; Kort, Daniel H; Prosser, Robert W; Paull, Daniel; Nestor, Michael W; Freeby, Matthew; Greenberg, Ellen; Goland, Robin S; Leibel, Rudolph L; Solomon, Susan L; Benvenisty, Nissim; Sauer, Mark V; Egli, Dieter

    2014-06-26

    The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.

  10. Stem cells and somatic cells: reprogramming and plasticity.

    PubMed

    Estrov, Zeev

    2009-01-01

    Recent seminal discoveries have significantly advanced the field of stem cell research and received worldwide attention. Improvements in somatic cell nuclear transfer (SCNT) technology, enabling the cloning of Dolly the sheep, and the derivation and differentiation of human embryonic stem cells raised hopes that normal cells could be generated to replace diseased or injured tissue. At the same time, in vitro and in vivo studies demonstrated that somatic cells of one tissue are capable of generating cells of another tissue. It was theorized that any cell might be reprogrammed, by exposure to a new environment, to become another cell type. This concept contradicts two established hypotheses: (1) that only specific tissues are generated from the endoderm, mesoderm, and ectoderm and (2) that tissue cells arise from a rare population of tissue-specific stem cells in a hierarchical fashion. SCNT, cell fusion experiments, and most recent gene transfer studies also contradict these hypotheses, as they demonstrate that mature somatic cells can be reprogrammed to regain pluripotent (or even totipotent) stem cell capacity. On the basis of the stem cell theory, hierarchical cancer stem cell differentiation models have been proposed. Cancer cell plasticity is an established phenomenon that supports the notion that cellular phenotype and function might be altered. Therefore, mechanisms of cellular plasticity should be exploited and the clinical significance of the cancer stem cell theory cautiously assessed.

  11. Stem cell systems and regeneration in planaria.

    PubMed

    Rink, Jochen C

    2013-03-01

    Planarians are members of the Platyhelminthes (flatworms). These animals have evolved a remarkable stem cell system. A single pluripotent adult stem cell type ("neoblast") gives rise to the entire range of cell types and organs in the planarian body plan, including a brain, digestive-, excretory-, sensory- and reproductive systems. Neoblasts are abundantly present throughout the mesenchyme and divide continuously. The resulting stream of progenitors and turnover of differentiated cells drive the rapid self-renewal of the entire animal within a matter of weeks. Planarians grow and literally de-grow ("shrink") by the food supply-dependent adjustment of organismal turnover rates, scaling body plan proportions over as much as a 50-fold size range. Their dynamic body architecture further allows astonishing regenerative abilities, including the regeneration of complete and perfectly proportioned animals even from tiny tissue remnants. Planarians as an experimental system, therefore, provide unique opportunities for addressing a spectrum of current problems in stem cell research, including the evolutionary conservation of pluripotency, the dynamic organization of differentiation lineages and the mechanisms underlying organismal stem cell homeostasis. The first part of this review focuses on the molecular biology of neoblasts as pluripotent stem cells. The second part examines the fascinating mechanistic and conceptual challenges posed by a stem cell system that epitomizes a universal design principle of biological systems: the dynamic steady state.

  12. Stem cell genome-to-systems biology.

    PubMed

    Chia, Na-Yu; Ng, Huck-Hui

    2012-01-01

    Stem cells are capable of extended proliferation and concomitantly differentiating into a plethora of specialized cell types that render them apropos for their usage as a form of regenerative medicine for cell replacement therapies. The molecular processes that underlie the ability for stem cells to self-renew and differentiate have been intriguing, and elucidating the intricacies within the genome is pertinent to enhance our understanding of stem cells. Systems biology is emerging as a crucial field in the study of the sophisticated nature of stem cells, through the adoption of multidisciplinary approaches which couple high-throughput experimental techniques with computational and mathematical analysis. This allows for the determination of the molecular constituents that govern stem cell characteristics and conjointly with functional validations via genetic perturbation and protein location binding analysis necessitate the construction of the complex transcriptional regulatory network. With the elucidation of protein-protein interaction, protein-DNA regulation, microRNA involvement as well as the epigenetic modifications, it is possible to comprehend the defining features of stem cells at the system level.

  13. Prion potency in stem cells biology.

    PubMed

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  14. Harnessing the apoptotic programs in cancer stem-like cells.

    PubMed

    Wang, Ying-Hua; Scadden, David T

    2015-09-01

    Elimination of malignant cells is an unmet challenge for most human cancer types even with therapies targeting specific driver mutations. Therefore, a multi-pronged strategy to alter cancer cell biology on multiple levels is increasingly recognized as essential for cancer cure. One such aspect of cancer cell biology is the relative apoptosis resistance of tumor-initiating cells. Here, we provide an overview of the mechanisms affecting the apoptotic process in tumor cells emphasizing the differences in the tumor-initiating or stem-like cells of cancer. Further, we summarize efforts to exploit these differences to design therapies targeting that important cancer cell population.

  15. Adult Stem Cell Therapy for Stroke: Challenges and Progress

    PubMed Central

    Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

    2016-01-01

    Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

  16. Nuclear Nox4 Role in Stemness Power of Human Amniotic Fluid Stem Cells

    PubMed Central

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

    2015-01-01

    Human amniotic fluid stem cells (AFSC) are an attractive source for cell therapy due to their multilineage differentiation potential and accessibility advantages. However the clinical application of human stem cells largely depends on their capacity to expand in vitro, since there is an extensive donor-to-donor heterogeneity. Reactive oxygen species (ROS) and cellular oxidative stress are involved in many physiological and pathophysiological processes of stem cells, including pluripotency, proliferation, differentiation, and stress resistance. The mode of action of ROS is also dependent on the localization of their target molecules. Thus, the modifications induced by ROS can be separated depending on the cellular compartments they affect. NAD(P)H oxidase family, particularly Nox4, has been known to produce ROS in the nucleus. In the present study we show that Nox4 nuclear expression (nNox4) depends on the donor and it correlates with the expression of transcription factors involved in stemness regulation, such as Oct4, SSEA-4, and Sox2. Moreover nNox4 is linked with the nuclear localization of redox sensitive transcription factors, as Nrf2 and NF-κB, and with the differentiation potential. Taken together, these results suggest that nNox4 regulation may have important effects in stem cell capability through modulation of transcription factors and DNA damage. PMID:26273418

  17. Cancer stem cell targeted therapy: progress amid controversies.

    PubMed

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-12-29

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy.

  18. Cancer stem cell targeted therapy: progress amid controversies

    PubMed Central

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  19. Measurement of human embryonic stem cell in the growing cycle

    NASA Astrophysics Data System (ADS)

    Li, X.; Zhao, L.; Oh, Steve K. W.; Chong, W. K.; Ong, J. K.; Chen, Allen K.; Choo, Andre B. H.

    2008-09-01

    A measurement and imaging system has been developed for in-line continuous measurement of live, unmodified, human embryonic stem cells (hESC). The measurement will not affect cell growth, structure, sterility and suitability for clinical use. The stem cell imaging system (SCIS) can be used to support the optimization of automated stem cell growth for invitro study and for high-volume bio-manufacture. This paper present the experimental and analysis for the optimization of system parameters. A non-linear lighting is developed to obtain a clear images. The individual cluster can be traced from day one to day two. The whole system is calibrated with measurement microscope and haemacytometer. The measurement accuracy is better than 90%.

  20. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells

    SciTech Connect

    Oka, Naoki; Soeda, Akio . E-mail: ccd29400@nyc.odn.ne.jp; Inagaki, Akihito; Onodera, Masafumi; Maruyama, Hidekazu; Hara, Akira; Kunisada, Takahiro; Mori, Hideki; Iwama, Toru

    2007-08-31

    There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche.

  1. Regulation of breast cancer stem cell features.

    PubMed

    Czerwinska, Patrycja; Kaminska, Bozena

    2015-01-01

    Cancer stem cells (CSCs) are rare, tumour-initiating cells that exhibit stem cell properties: capacity of self-renewal, pluripotency, highly tumorigenic potential, and resistance to therapy. Cancer stem cells have been characterised and isolated from many cancers, including breast cancer. Developmental pathways, such as the Wnt/β-catenin, Notch/γ-secretase/Jagged, Shh (sonic hedgehog), and BMP signalling pathways, which direct proliferation and differentiation of normal stem cells, have emerged as major signalling pathways that contribute to the self-renewal of stem and/or progenitor cells in a variety of organs and cancers. Deregulation of these signalling pathways is frequently linked to an epithelial-mesenchymal transition (EMT), and breast CSCs often possess properties of cells that have undergone the EMT process. Signalling networks mediated by microRNAs and EMT-inducing transcription factors tie the EMT process to regulatory networks that maintain "stemness". Recent studies have elucidated epigenetic mechanisms that control pluripotency and stemness, which allows an assessment on how embryonic and normal tissue stem cells are deregulated during cancerogenesis to give rise to CSCs. Epigenetic-based mechanisms are reversible, and the possibility of "resetting" the abnormal cancer epigenome by applying pharmacological compounds targeting epigenetic enzymes is a promising new therapeutic strategy. Chemoresistance of CSCs is frequently driven by various mechanisms, including aberrant expression/activity of ABC transporters, aldehyde dehydrogenase and anti-oncogenic proteins (i.e. BCL2, B-cell lymphoma-2), enhanced DNA damage response, activation of pro-survival signalling pathways, and epigenetic deregulations. Despite controversy surrounding the CSC hypothesis, there is substantial evidence for their role in cancer, and a number of drugs intended to specifically target CSCs have entered clinical trials.

  2. Ethical issues in stem cell research.

    PubMed

    Lo, Bernard; Parham, Lindsay

    2009-05-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson's disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies.

  3. Ethical Issues in Stem Cell Research

    PubMed Central

    Lo, Bernard; Parham, Lindsay

    2009-01-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies. PMID:19366754

  4. FDA Warns About Stem Cell Claims

    MedlinePlus

    ... perpetrators who expose the American public to the dangers of unapproved stem cells and ensure that they ... You Need to Know More in Consumer Updates Animal & Veterinary Children's Health Cosmetics Dietary Supplements Drugs Food ...

  5. Becoming a Blood Stem Cell Donor

    MedlinePlus Videos and Cool Tools

    ... donors at http://www.marrow.org . Category Science & Technology License Standard YouTube License Show more Show less ... views 10:58 Susan Solomon: The promise of research with stem cells - Duration: 14:59. TED 61, ...

  6. Hematopoietic stem cell engineering at a crossroads.

    PubMed

    Rivière, Isabelle; Dunbar, Cynthia E; Sadelain, Michel

    2012-02-02

    The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.

  7. De Novo Kidney Regeneration with Stem Cells

    PubMed Central

    Yokote, Shinya; Yamanaka, Shuichiro; Yokoo, Takashi

    2012-01-01

    Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration. PMID:23251079

  8. Will embryonic stem cells change health policy?

    PubMed

    Sage, William M

    2010-01-01

    Embryonic stem cells are actively debated in political and public policy arenas. However, the connections between stem cell innovation and overall health care policy are seldom elucidated. As with many controversial aspects of medical care, the stem cell debate bridges to a variety of social conversations beyond abortion. Some issues, such as translational medicine, commercialization, patient and public safety, health care spending, physician practice, and access to insurance and health care services, are core health policy concerns. Other issues, such as economic development, technologic progress, fiscal politics, and tort reform, are only indirectly related to the health care system but are frequently seen through a health care lens. These connections will help determine whether the stem cell debate reaches a resolution, and what that resolution might be.

  9. Current progress of human trials using stem cell therapy as a treatment for diabetes mellitus

    PubMed Central

    Cheng, Shuk Kei; Park, Elisse Y; Pehar, Andjela; Rooney, Alexandra C; Gallicano, G. Ian

    2016-01-01

    Diabetes mellitus affects millions of people worldwide, and is associated with serious complications that affect nearly all body systems. Because of the severity of this global health concern, there is a great deal of research being performed on alternative treatments and possible cures. Previous treatments for diabetes have included exogenous insulin injection and pancreatic islet transplantations. These treatment methods have several limitations; thus, the use of stem cells in treating diabetes is currently a significant area of research. This review outlines current research on stem cell therapy for diabetes mellitus. Numerous studies have been performed on animals using various types of stem cells, including mesenchymal stem cells and embryonic stem cells. Moreover, results and limitations of animal studies have been confirmed in various clinical trials. Overall, stem cell treatment shows prospective advantages over insulin injections and other current treatment options, and ongoing clinical trials suggest that this therapy may be a viable treatment option for diabetics in the near future. PMID:27853629

  10. Generation of pluripotent stem cells from adult human testis.

    PubMed

    Conrad, Sabine; Renninger, Markus; Hennenlotter, Jörg; Wiesner, Tina; Just, Lothar; Bonin, Michael; Aicher, Wilhelm; Bühring, Hans-Jörg; Mattheus, Ulrich; Mack, Andreas; Wagner, Hans-Joachim; Minger, Stephen; Matzkies, Matthias; Reppel, Michael; Hescheler, Jürgen; Sievert, Karl-Dietrich; Stenzl, Arnulf; Skutella, Thomas

    2008-11-20

    Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

  11. Cell therapy using induced pluripotent stem cells or somatic stem cells: this is the question.

    PubMed

    Somoza, Rodrigo A; Rubio, Francisco J

    2012-05-01

    A lot of effort has been developed to bypass the use of embryonic stem cells (ES) in human therapies, because of several concerns and ethical issues. Some unsolved problems of using stem cells for human therapies, excluding the human embryonic origin, are: how to regulate cell plasticity and proliferation, immunological compatibility, potential adverse side-effects when stem cells are systemically administrated, and the in vivo signals to rule out a specific cell fate after transplantation. Currently, it is known that almost all tissues of an adult organism have somatic stem cells (SSC). Whereas ES are primary involved in the genesis of new tissues and organs, SSC are involved in regeneration processes, immuno-regulatory and homeostasis mechanisms. Although the differentiating potential of ES is higher than SSC, several studies suggest that some types of SSC, such as mesenchymal stem cells (MSC), can be induced epigenetically to differentiate into tissue-specific cells of different lineages. This unexpected pluripotency and the variety of sources that they come from, can make MSC-like cells suitable for the treatment of diverse pathologies and injuries. New hopes for cell therapy came from somatic/mature cells and the discovery that could be reprogrammed to a pluripotent stage similar to ES, thus generating induced pluripotent stem cells (iPS). For this, it is necessary to overexpress four main reprogramming factors, Sox2, Oct4, Klf4 and c-Myc. The aim of this review is to analyze the potential and requirements of cellular based tools in human therapy strategies, focusing on the advantage of using MSC over iPS.

  12. Matrix elasticity directs stem cell lineage specification

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2010-03-01

    Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. [4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).

  13. Mesenchymal stem cells: the fibroblasts’ new clothes?

    PubMed Central

    Haniffa, Muzlifah A.; Collin, Matthew P.; Buckley, Christopher D.; Dazzi, Francesco

    2009-01-01

    Mesenchymal stem cells are adherent stromal cells, initially isolated from the bone marrow, characterized by their ability to differentiate into mesenchymal tissues such as bone, cartilage and fat. They have also been shown to suppress immune responses in vitro. Because of these properties, mesenchymal stem cells have recently received a very high profile. Despite the dramatic benefits reported in early phase clinical trials, their functions remain poorly understood. Particularly, several questions remain concerning the origin of mesenchymal stem cells and their relationship to other stromal cells such as fibroblasts. Whereas clear gene expression signatures are imprinted in stromal cells of different anatomical origins, the anti-proliferative effects of mesenchymal stem cells and fibroblasts and their potential to differentiate appear to be common features between these two cell types. In this review, we summarize recent studies in the context of historical and often neglected stromal cell literature, and present the evidence that mesenchymal stem cells and fibroblasts share much more in common than previously recognized. PMID:19109217

  14. Stem Cell Therapy for the Inner Ear

    PubMed Central

    Okano, Takayuki

    2012-01-01

    In vertebrates, perception of sound, motion, and balance is mediated through mechanosensory hair cells located within the inner ear. In mammals, hair cells are only generated during a short period of embryonic development. As a result, loss of hair cells as a consequence of injury, disease, or genetic mutation, leads to permanent sensory deficits. At present, cochlear implantation is the only option for profound hearing loss. However, outcomes are still variable and even the best implant cannot provide the acuity of a biological ear. The recent emergence of stem cell technology has the potential to open new approaches for hair cell regeneration. The goal of this review is to summarize the current state of inner ear stem cell research from a viewpoint of its clinical application for inner ear disorders to illustrate how complementary studies have the potential to promote and refine stem cell therapies for inner ear diseases. The review initially discusses our current understanding of the genetic pathways that regulate hair cell formation from inner ear progenitors during normal development. Subsequent sections discuss the possible use of endogenous inner ear stem cells to induce repair as well as the initial studies aimed at transplanting stem cells into the ear. PMID:22514095

  15. Measuring the Aging Process in Stem Cells

    PubMed Central

    Liu, Yi; Van Zant, Gary; Liang, Ying

    2015-01-01

    Summary Stem cells persist in replenishing functional mature cells throughout life by self-renewal and multilineage differentiation. Hematopoietic stem cells (HSCs) are among the best-characterized and understood stem cells, and they are responsible for the life-long production of all lineages of blood cells. HSCs are a heterogeneous population containing lymphoid-biased, myeloid-biased and balanced subsets. HSCs undergo age-associated phenotypic and functional changes, and the composition of the HSC pool alters with aging. HSCs and their lineage-biased subfractions can be identified and analyzed by flow cytometry based on cell surface makers. Fluorescence-activated cell sorting (FACS) enables the isolation and purification of HSCs that greatly facilitates the mechanistic study of HSCs and their aging process at both cellular and molecular levels. The mouse model has been extensively used in HSC aging study. Bone marrow cells are isolated from young and old mice and stained with fluorescence-conjugated antibodies specific for differentiated and stem cells. HSCs are selected based on the negative expression of lineage markers and positive selection for several sets of stem cell markers. Lineage-biased HSCs can be further distinguished by the level of SLAM/CD150 expression and the extent of Hoechst efflux. PMID:25388383

  16. 3 CFR - Guidelines for Human Stem Cell Research

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the...

  17. Deriving blood stem cells from pluripotent stem cells for research and therapy.

    PubMed

    Daley, George Q

    2014-01-01

    Embryonic stem cells and induced pluripotent stem cells offer promise for research and treatment of hematologic diseases. While broad clinical application in humans is still a distant prospect, there are promising near-term applications in transfusion of platelets and red blood cells.

  18. Multiple myeloma cancer stem cells

    PubMed Central

    Gao, Minjie; Kong, Yuanyuan; Yang, Guang; Gao, Lu; Shi, Jumei

    2016-01-01

    Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contributes to disease relapse, but the mechanisms of drug resistance have not been fully understood. The major signaling pathways involved in the regulation of self-renewal and differentiation of MMSCs include Hedgehog (Hh), Wingless (Wnt), Notch and PI3K/Akt/mTOR. However, the precise role of these signaling pathways needs to be clarified. It has been reported that the microRNA profile of MMSCs is remarkably different than that of non-MMSCs. Therefore, the search for targeting MMSCs has also been focused on microRNAs. Complex and mutual interactions between the MMSC and the surrounding bone marrow (BM) microenvironment sustain self-renewal and survival of MMSC. However, the required molecules for the interaction of the MMSC and the surrounding BM microenvironment need to be further identified. In this review, we summarize the current state of knowledge of MMSCs regarding their phenotype, mechanisms of drug resistance, signaling pathways that regulate MMSCs self-renewal and differentiation, abnormal microRNAs expression, and their interactions with the BM microenvironment. PMID:27007154

  19. When stem cells grow old: phenotypes and mechanisms of stem cell aging

    PubMed Central

    Schultz, Michael B.; Sinclair, David A.

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. PMID:26732838

  20. Development in intracerebral stem cell grafts

    PubMed Central

    Reyes, Stephanny; Tajiri, Naoki; Borlongan, Cesar V.

    2015-01-01

    The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson’s disease, Huntington’s disease, stroke, and traumatic brain injury. PMID:25739415

  1. Regeneration of the retina: toward stem cell therapy for degenerative retinal diseases.

    PubMed

    Jeon, Sohee; Oh, Il-Hoan

    2015-04-01

    Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases.

  2. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  3. Perspectives and controversies in the field of stem cell research.

    PubMed

    Romano, Gaetano

    2006-09-01

    The fourth annual meeting of the International Society for Stem Cell Research focused on a number of pressing issues, including: (I) the need to better characterize the biology of stem cells; (II) the need to exploit and optimize the great therapeutic potential of stem cells in tissue regeneration; (III) ethical and safety considerations related to the use of human embryonic stem cells; (IV) the contribution of adult stem cells to carcinogenesis; (V) the need to investigate the biology of cancer stem cells. The purpose of this report is to summarize the current status of stem cell research, as surmised by the proceedings of this meeting.

  4. Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells.

    PubMed

    Zhao, Zhu-Ran; Yu, Wei-Dong; Shi, Cheng; Liang, Rong; Chen, Xi; Feng, Xiao; Zhang, Xue; Mu, Qing; Shen, Huan; Guo, Jing-Zhu

    2017-01-01

    Overexpression of receptor-interacting protein 140 (RIP140) promotes neuronal differentiation of N2a cells via extracellular regulated kinase 1/2 (ERK1/2) signaling. However, involvement of RIP140 in human neural differentiation remains unclear. We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells. Moreover, RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation, and positively correlated with the neural stem cell marker Nestin during later stages. Thus, ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.

  5. Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells

    PubMed Central

    Zhao, Zhu-ran; Yu, Wei-dong; Shi, Cheng; Liang, Rong; Chen, Xi; Feng, Xiao; Zhang, Xue; Mu, Qing; Shen, Huan; Guo, Jing-zhu

    2017-01-01

    Overexpression of receptor-interacting protein 140 (RIP140) promotes neuronal differentiation of N2a cells via extracellular regulated kinase 1/2 (ERK1/2) signaling. However, involvement of RIP140 in human neural differentiation remains unclear. We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells. Moreover, RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation, and positively correlated with the neural stem cell marker Nestin during later stages. Thus, ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced. PMID:28250757

  6. Inner ear cell therapy targeting hereditary deafness by activation of stem cell homing factors.

    PubMed

    Kamiya, Kazusaku

    2015-01-01

    Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation. Inner ear cell therapy for sensorineural hearing loss has been expected to be an effective therapy for hereditary deafness. Previously, we developed a novel strategy for inner ear cell therapy using bone marrow mesenchymal stem cells as a supplement for cochlear fibrocytes functioning for cochlear ion transport. For cell therapy targeting hereditary deafness, a more effective cell delivery system to induce the stem cells into cochlear tissue is required, because gene mutations affect all cochlear cells cochlear cells expressing genes such as GJB2 encoding CX26. Stem cell homing is one of the crucial mechanisms to be activated for efficient cell delivery to the cochlear tissue. In our study, monocyte chemotactic protein-1, stromal cell-derived factor-1 and their receptors were found to be a key regulator for stem cell recruitment to the cochlear tissue. Thus, the activation of stem cell homing may be an efficient strategy for hearing recovery in hereditary deafness.

  7. Stem cell technologies: regulation, patents and problems.

    PubMed

    Then, Shih-Ning

    2004-11-01

    Human embryonic stem cell research promises to deliver in the future a whole range of therapeutic treatments, but currently governments in different jurisdictions must try to regulate this burgeoning area. Part of the problem has been, and continues to be, polarised community opinion on the use of human embryonic stem cells for research. This article compares the approaches of the Australian, United Kingdom and United States governments in regulating human embryonic stem cell research. To date, these governments have approached the issue through implementing legislation or policy to control research. Similarly, the three jurisdictions have viewed the patentability of human embryonic stem cell technologies in their own ways with different policies being adopted by the three patent offices. This article examines these different approaches and discusses the inevitable concerns that have been raised due to the lack of a universal approach in relation to the regulation of research; the patenting of stem cell technologies; and the effects patents granted are having on further human embryonic stem cell research.

  8. Building Epithelial Tissues from Skin Stem Cells

    PubMed Central

    Fuchs, E.; Nowak, J.A.

    2009-01-01

    The skin epidermis and its appendages provide a protective barrier that guards against loss of fluids, physical trauma, and invasion by harmful microbes. To perform these functions while c