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（由申请人提供）：使用中枢神经系统干的移植策略 细胞具有替代失去的神经元回路的巨大潜力 帕金森病和其他神经系统疾病。中枢神经系统移植能力 如果要提供治疗效果，移植后的存活至关重要 为广大PD患者带来福音。此外，还必须有足够的 供体细胞的来源。该提案的目的是插入人类 端粒酶基因 (hTERT) 转入人类死后神经祖细胞 （HPCP）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 hTERT 的异位表达是一种合乎逻辑的方法 使这些细胞在培养物中永生化并降低其敏感性 移植后发生细胞凋亡。确定异位的影响 HPCP 中端粒酶的表达对群体倍增、细胞凋亡抵抗力的影响 分化成所有中枢神经系统细胞类型的能力是至关重要的第一步 在研究这些方法时。评估活力、增殖和 移植到 6-OHDA 损伤大鼠模型中的 hTERT+ HPCP 的不同命运 帕金森病的诊断以及移植后功能恢复的评估 接收者将进一步描述这些方法可能的程度 为未来神经系统疾病的干细胞治疗做出贡献。对于 治疗帕金森？疾病，未来的步骤可能包括将这些结合起来 具有可能在一部分人中诱导多巴胺能命运的策略的方法 这些祖先。