Minority predoctoral fellowship program

描述(由调查员提供)：本提案旨在探索 人骨髓来源的多潜能成体干细胞的治疗潜力 (MAPC)用于神经移植和修复。MAPC可以提供(1)来源 用于细胞替代治疗的移植组织和(2)基因治疗载体 纠正中枢神经系统的代谢或神经化学缺陷。我们将测试 人MAPC是否可以迁移并经历神经元、部位特异性 将其移植到新生大鼠体内进行体内分化。自.以来 胆碱能基底前脑变性与认知功能减退相关 在阿尔茨海默病？S病中，我们将特别关注 MAPC在该区域移植时的胆碱能分化。体外 神经生长因子基因转移已被证明是一种合适的方法 改善与基底神经退行性变相关的认知缺陷 前脑胆碱能系统，如在衰老和阿尔茨海默病？S病中所见。AS基因 治疗载体，我们感兴趣的是确定 神经生长因子分泌的MAPC移植改善动物认知功能障碍 伴有部分胆碱能免疫渗漏。因此，我们的实验将测试 MAPC作为神经移植现成来源的作用 组织除了具有易于膨胀的优点外， 在体外分化和基因操作方面，也体现了独特的 自体移植的前景展望。

DESCRIPTION (provided by investigator): This proposal intends to explore the therapeutic potential of human bone marrow derived multipotent adult stem cells (MAPCs) for neural transplantation and repair. MAPCs could provide a (1) source of grafting tissue for cell replacement therapies and (2) gene therapy vehicles to correct metabolic or neurochemical deficiencies in the CNS. We will test whether human MAPCs can migrate and undergo neuronal, site-specific differentiation in vivo by transplanting them into neonatal rats. Since cholinergic basal forebrain degeneration is correlated with cognitive decline in Alzheimer?s disease, we will particularly addresss the potential for cholinergic differentiation of MAPCs when transplanted in this region. Ex-vivo nerve growth factor gene transfer has been shown to be a suitable approach to improve the cognitive deficits associated with degeneration of the basal forebrain cholinergic system, as seen in aging and Alzheimer?s disease. As gene therapy vehicles, we are interested in determining the effectiveness of NGF-secreting MAPCs transplants to ameliorate the cognitive deficits of animals with partial cholinergic immunolesions. Therefore, our experiments will test the role for MAPCs as a readily available source for neural transplantation tissue that besides the advantage of being amenable to expansion, differentiation and genetic manipulation in vitro, also embodies the unique prospect for autologous transplantation.