ES CELL TRANSPLANTATION AFTER SPINAL CORD INJURY

脊髓损伤后 ES 细胞移植

• 批准号: 6477172
• 负责人: EUGENE M JOHNSON
• 金额: $ 106.78万
• 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/6477172
• 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.

要求赠款资金支持一项新的研究计划项目，旨在启动探索胚胎茎（ES）细胞移植对脊髓损伤后恢复功能的恢复功能的潜力。拟议的项目团队的成员已经开发了与小鼠ES细胞一起工作的经验，可以分化神经谱系，减少神经系统中细胞死亡的方法以及创伤性脊髓损伤的啮齿动物模型。在构成本提案特定背景的实验中，项目团队成员获得了证据表明，可以成功将小鼠ES细胞衍生的神经谱系细胞（ESNLC）成功移植到Syrinx/Cyst中，这些Syrinx/Cyst形成了大鼠脊髓造成9天的损伤。这些移植的ESNLC至少存活了数周，部分填充了Syrinx并迁移到宿主组织中，并表达了分化的少突胶质细胞，星形胶质细胞和神经元的标记。要求的计划项目资金将使项目团队成员能够以系统的和假设为驱动的方式在这些早期实验的基础上进行。基于直接观察到，大多数移植的ESNLC在移植后的头48小时死亡，尤其是神经元在随后的几天中继续死亡，此处的实验的重点将是通过药理和遗传学工程进行移植的ESNLC的存活，旨在通过药理学和遗传工程来阻止Apoptosis和Ixcitox，而旨在通过药理和遗传学工程进行促进。可以预料，随后几年所做的工作可能是针对其他方式优化ESNLC移植程序的。