Telomerase re-expression in postmorterm CNS Progenitors.

死后中枢神经系统祖细胞中端粒酶的重新表达。

• 批准号: 6529774
• 负责人: Robert Mark Richardson
• 金额: $ 3.13万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6529774
• 关键词: Parkinson's disease; apoptosis; cell differentiation; cell line; cell proliferation; cell type; central nervous system; gene expression; human tissue; laboratory rat; nervous system regeneration; neurons; postmortem; stem cell transplantation; stem cells; telomerase; transfection; transposon /insertion element; tyrosine 3 monooxygenase

DESCRIPTION (provided by applicant): Transplantation strategies using CNS stem cells offer tremendous potential for replacing neuronal circuitry lost to Parkinson?s disease and other neurological disorders. The ability of CNS grafts to survive after transplant is crucial if therapeutic benefit is to be provided to a large number of patients with PD. Additionally, there must be an adequate source of donor cells. The purpose of this proposal is to insert the human telomerase gene (hTERT) into human postmortem-derived neural progenitor cells (HPCPs) in order to improve the survival of transplanted cells and ultimately increase the proliferation of desired cell types. HPCPs provide an easily accessible donor source, and ectopic expression of hTERT is a logical means by which to immortalize these cells in culture and decrease their susceptibility to apoptotic death following transplantation. Determining the effect of ectopic telomerase expression in HPCPs on population doublings, resistance to apoptosis and ability to differentiate into all CNS cell types is the crucial first step in investigating these methods. Assessing the viability, proliferation and differential fates of hTERT+ HPCPs transplanted to a 6-OHDA lesioned rat model of Parkinson?s disease, and evaluating functional recovery in transplant recipients will further characterize the extent to which these approaches may contribute to future stem cell therapy for neurological disorders. For the treatment of Parkinson? disease, a future step may include combining these methods with strategies likely to induce a dopaminergic fate among a subset of these progenitors.

描述(申请人提供)：使用中枢神经系统干细胞的移植策略 细胞提供了巨大的潜力来取代丢失的神经元电路 帕金森？S病等神经系统疾病。中枢神经系统移植物的能力 如果要提供治疗益处，移植后的存活是至关重要的 给大量的帕金森病患者。此外，必须有足够的 供体细胞的来源。这项提议的目的是将人类 端粒酶基因(HTERT)导入人死后神经前体细胞的研究 (HPCPs)以提高移植细胞的存活率，并最终 增加所需细胞类型的增殖。HPCP提供了一个轻松的 可获得供体来源，hTERT的异位表达是一种逻辑手段，通过 使这些细胞在培养中永生并降低它们的敏感性 移植后的细胞凋亡性死亡。确定异位的影响 端粒酶在群体倍增的HPCP中的表达与抗凋亡 能够分化为所有类型的中枢神经系统细胞是关键的第一步 在研究这些方法时。评估其生存能力、增殖能力和 HTERT+HPCPs移植于6-羟基多巴胺损伤大鼠模型的不同命运 帕金森病、S病与移植后功能恢复的关系 接受者将进一步描述这些方法可以在多大程度上 为未来神经疾病的干细胞治疗做出贡献。对于 帕金森的治疗？疾病，未来的步骤可能包括结合这些 这些方法的策略可能会在一组 这些祖先。