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（由申请方提供）：使用CNS股骨柄的移植策略 细胞提供了巨大的潜力， 帕金森？的疾病和其他神经系统疾病。CNS移植物的能力 如果要提供治疗效果， 大量的PD患者。此外，必须有一个足够的 供体细胞的来源。该提案的目的是插入人类 端粒酶基因转染人死后神经前体细胞 （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提供了一个简单的 可获得的供体来源，hTERT的异位表达是一种合乎逻辑的手段， 在培养中使这些细胞永生化并降低它们的易感性 移植后的凋亡性死亡。确定异位妊娠的影响 端粒酶在HPCPs中表达对群体增殖、抗凋亡的影响 而分化成所有类型的中枢神经系统细胞是关键的第一步 研究这些方法。评估其生存能力、增殖能力和 hTERT+ HPCPs移植到6-OHDA损伤大鼠模型中的不同命运 帕金森？的疾病，并评估移植功能恢复 接受者将进一步描述这些方法可以在多大程度上 有助于未来神经系统疾病的干细胞治疗。为 治疗帕金森？疾病，未来的步骤可能包括将这些 方法与策略可能诱导多巴胺能的命运之间的一个子集， 这些祖先。