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.
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