Current Issue : July - September Volume : 2013 Issue Number : 3 Articles : 5 Articles
Introduction: A feature which makes stem cells promising candidates for cell therapy is their ability to migrate\r\neffectively into damaged or diseased tissues. Recent reports demonstrated the increased motility of human\r\nmesenchymal stem cells (hMSC) grown under hypoxic conditions compared to normoxic cells. However, the\r\ndirectional migration of hMSC cultured in hypoxia has not been investigated. In this study we examined the in\r\nvitro transmembrane migration of hMSC permanently cultured in hypoxia in response to various cytokines. We also\r\nstudied the involvement of RhoA, a molecule believed to play an essential role in the migration of MSC via\r\nreorganization of the cytoskeleton.\r\nMethods: We compared the directional migration of human hMSCs grown permanently under normal (21%,\r\nnormoxic) and low O2 (5%, hypoxic) conditions until passage 4 using an in vitro transmembrane migration assay. A\r\nseries of 17 cytokines was used to induce chemotaxis. We also compared the level of GTP-bound RhoA in the cell\r\nextracts of calpeptin-activated hypoxic and normoxic hMSC.\r\nResults: We found that hMSC cultured in hypoxia demonstrate markedly higher targeted migration activity\r\ncompared to normoxic cells, particularly towards wound healing cytokines, including those found in ischemic and\r\nmyocardial infarction. We also demonstrated for the first time that hMSC are dramatically more sensitive to\r\nactivation of RhoA.\r\nConclusions: The results of this study indicate that high directional migration of hMSCs permanently grown in\r\nhypoxia is associated with the enhanced activation of RhoA. The enhanced migratory capacity of hypoxic hMSC\r\nwould further suggest their potential advantages for clinical applications....
Introduction: Stimulating the commitment of implanted dystrophin+ muscle-derived stem cells (MDSCs) into\r\nmyogenic, as opposed to lipofibrogenic lineages, is a promising therapeutic strategy for Duchenne muscular\r\ndystrophy (DMD).\r\nMethods: To examine whether counteracting myostatin, a negative regulator of muscle mass and a pro-lipofibrotic\r\nfactor, would help this process, we compared the in vitro myogenic and fibrogenic capacity of MDSCs from wildtype\r\n(WT) and myostatin knockout (Mst KO) mice under various modulators, the expression of key stem cell and\r\nmyogenic genes, and the capacity of these MDSCs to repair the injured gastrocnemius in aged dystrophic mdx\r\nmice with exacerbated lipofibrosis.\r\nResults: Surprisingly, the potent in vitro myotube formation by WT MDSCs was refractory to modulators of\r\nmyostatin expression or activity, and the Mst KO MDSCs failed to form myotubes under various conditions, despite\r\nboth MDSC expressing Oct 4 and various stem cell genes and differentiating into nonmyogenic lineages. The\r\ngenetic inactivation of myostatin in MDSCs was associated with silencing of critical genes for early myogenesis\r\n(Actc1, Acta1, and MyoD). WT MDSCs implanted into the injured gastrocnemius of aged mdx mice significantly\r\nimproved myofiber repair and reduced fat deposition and, to a lesser extent, fibrosis. In contrast to their in vitro\r\nbehavior, Mst KO MDSCs in vivo also significantly improved myofiber repair, but had few effects on lipofibrotic\r\ndegeneration.\r\nConclusions: Although WT MDSCs are very myogenic in culture and stimulate muscle repair after injury in the\r\naged mdx mouse, myostatin genetic inactivation blocks myotube formation in vitro, but the myogenic capacity is\r\nrecovered in vivo under the influence of the myostatin+ host-tissue environment, presumably by reactivation of\r\nkey genes originally silenced in the Mst KO MDSCs....
Introduction: Nervous system injuries comprise a diverse group of disorders that include traumatic brain injury\r\n(TBI). The potential of mesenchymal stem cells (MSCs) to differentiate into neural cell types has aroused hope for\r\nthe possible development of autologous therapies for central nervous system injury.\r\nMethods: In this study we isolated and characterized a human peripheral blood derived (HPBD) MSC population\r\nwhich we examined for neural lineage potential and ability to migrate in vitro and in vivo. HPBD CD133+, ATPbinding\r\ncassette sub-family G member 2 (ABCG2)+, C-X-C chemokine receptor type 4 (CXCR4)+ MSCs were\r\ndifferentiated after priming with b-mercaptoethanol (b-ME) combined with trans-retinoic acid (RA) and culture in\r\nneural basal media containing basic fibroblast growth factor (FGF2) and epidermal growth factor (EGF) or coculture\r\nwith neuronal cell lines. Differentiation efficiencies in vitro were determined using flow cytometry or\r\nfluorescent microscopy of cytospins made of FACS sorted positive cells after staining for markers of immature or\r\nmature neuronal lineages. RA-primed CD133+ABCG2+CXCR4+ human MSCs were transplanted into the lateral\r\nventricle of male Sprague-Dawley rats, 24 hours after sham or traumatic brain injury (TBI). All animals were\r\nevaluated for spatial memory performance using the Morris Water Maze (MWM) Test. Histological examination of\r\nsham or TBI brains was done to evaluate MSC survival, migration and differentiation into neural lineages. We also\r\nexamined induction of apoptosis at the injury site and production of MSC neuroprotective factors.\r\nResults: CD133+ABCG2+CXCR4+ MSCs consistently expressed markers of neural lineage induction and were\r\npositive for nestin, microtubule associated protein-1b (MAP-1b), tyrosine hydroxylase (TH), neuron specific nuclear\r\nprotein (NEUN) or type III beta-tubulin (Tuj1). Animals in the primed MSC treatment group exhibited MWM latency\r\nresults similar to the uninjured (sham) group with both groups showing improvements in latency. Histological\r\nexamination of brains of these animals showed that in uninjured animals the majority of MSCs were found in the\r\nlateral ventricle, the site of transplantation, while in TBI rats MSCs were consistently found in locations near the\r\ninjury site. We found that levels of apoptosis were less in MSC treated rats and that MSCs could be shown to\r\nproduce neurotropic factors as early as 2 days following transplantation of cells. In TBI rats, at 1 and 3 months post\r\ntransplantation cells were generated which expressed markers of neural lineages including immature as well as\r\nmature neurons....
Introduction: Neural stem cell transplantation is a promising tool for the restoration of the enteric nervous system\r\nin a variety of motility disorders. However, limited cell viability after transplantation has restricted its regenerative\r\ncapacity. The aim of this study was to evaluate the effect of transplantation of neuroepithelial stem cell (NESC)\r\noverexpressing anti-apoptotic gene Bcl-2 on the survival, differentiation and function of grafted cells in rat\r\naganglionic colon.\r\nMethods: NESCs were isolated from neural tube of embryonic rat (embryonic day 11.5) and manipulated to\r\noverexpress the Bcl-2 gene. After transplantation into the benzalkonium chloride-induced rat aganglionic colon,\r\ngrafted cells were visualized in colonic sections. Apoptosis and differentiation of the implanted cells were assessed\r\n1, 4 and 8 weeks post transplantation, respectively. Eight weeks post transplantation, neuronal function of the\r\ncolon was assessed by measuring the response of muscle strips to electrical field stimulation.\r\nResults: Transplantation with Bcl-2-NESCs reduced apoptosis within the transplant at 1 week compared with the\r\nvector-NESC grafted group. Our findings also indicated that overexpression of Bcl-2 in the transplanted NESCs\r\nenhanced differentiation into PGP9.5-positive and neuronal nitric oxide synthase-positive neurons at 8-week\r\nassessment. Moreover, electrical field stimulation-induced relaxation of colonic strips was also significantly increased\r\nin the Bcl-2-NESC grafted group.\r\nConclusion: Transplantation of NESCs genetically modified to overexpress Bcl-2 may have value for enhancing\r\nsurvival and neurogenesis of grafted cells in the adult gut environment and for improving the efficacy of stem cell\r\ntherapy following a broad range of gastrointestinal motility disorders....
Stem cells have the significant latent to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can multiply without limit to replenish other cells as long as the person is alive. When a stem cell multiplies, every new cell has the latent to either remain a stem cell or become another type of cell with a more dedicated function, such as a brain cell or a red blood cell. Research on stem cells is advancing information about how an organism develops from a single cell and how healthy cells substitute damaged cells in adult organisms. This promising area of science leading scientists to explore the possibility of cell-based therapies to treat diseases, which referred as regenerative or reparative medicine. The vast opportunity in medicine is regenerative medicine wherein stem cell therapy is going to play a major role. This review highlights the stem cell therapies that have potential to cure numerous life threatening diseases as well future perspectives in the area of stem cell research....
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