ES CELL TRANSPLANTATION AFTER SPINAL CORD INJURY

脊髓损伤后 ES 细胞移植

• 批准号: 6625482
• 负责人: EUGENE M JOHNSON
• 金额: $ 106.77万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-17 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625482
• 关键词: embryonic stem cell; spinal cord injury; stem cell transplantation

Grant funds are requested to support a new research Program Project aimed at initiating an exploration of the potential of embryonic stem (ES) cell transplantation for restoring lost functions after spinal cord injury. Members of the proposed Project team have already developed experience working with mouse ES cells differentiated down neural lineages, methods for reducing cell death in the nervous system, and rodent models of traumatic spinal cord injury. In the experiments that form the specific background for the present proposal, Project team members have obtained evidence that mouse ES-cell derived neural lineage cells (ESNLCs) can be successfully transplanted into the syrinx/cyst that forms nine days after impact injury to the rat spinal cord . These transplanted ESNLCs survived for at least many weeks, partially filling the syrinx and migrating into host tissue, and expressed markers for differentiated oligodendrocytes, astrocytes, and neurons. The requested Program Project funding would enable Project team members to build on these early experiments in a systematic and hypothesis-driven fashion. Based on direct observations that a majority of transplanted ESNLCs die over the first 48 hours following transplantation and that neurons in particular continue to die over subsequent days, the emphasis of the experiments proposed here will be on improving the survival of transplanted ESNLCs through pharmacological and genetic engineering approaches aimed at blocking apoptosis and excitotoxicity. It is anticipated that work performed in subsequent years may be directed at optimizing the ESNLC transplantation procedure in other ways.

请求拨款支持一项新的研究计划项目，该项目旨在启动探索胚胎干（ES）细胞移植恢复脊髓损伤后丧失功能的潜力。拟议项目团队的成员已经积累了使用小鼠 ES 细胞分化为神经谱系、减少神经系统细胞死亡的方法以及创伤性脊髓损伤的啮齿动物模型的经验。在构成本提案具体背景的实验中，项目团队成员获得了证据，表明小鼠 ES 细胞衍生的神经谱系细胞 (ESNLC) 可以成功移植到大鼠脊髓冲击损伤九天后形成的空洞/囊肿中。这些移植的 ESNLC 存活至少数周，部分填充空洞并迁移到宿主组织中，并表达分化的少突胶质细胞、星形胶质细胞和神经元的标记物。所请求的计划项目资金将使项目团队成员能够以系统和假设驱动的方式在这些早期实验的基础上进行开发。根据直接观察到大多数移植的 ESNLC 在移植后的前 48 小时内死亡，特别是神经元在随后的几天内继续死亡，这里提出的实验的重点将是通过旨在阻止细胞凋亡和兴奋性毒性的药理学和基因工程方法来提高移植的 ESNLC 的存活率。预计随后几年进行的工作可能会以其他方式优化 ESNLC 移植程序。