Percutaneous delivery of stem cells for spinal cord injury

经皮递送干细胞治疗脊髓损伤

基本信息

批准号：
7013658
负责人：
Itzhak Fischer
金额：
$ 13.96万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7013658
关键词：
artificial immunosuppression autologous transplantation bone marrow brain derived neurotrophic factor cell death cerebrospinal fluid connective tissue cells hematopoietic tissue transplantation homologous transplantation immunocytochemistry laboratory rat lumbar puncture nervous system disorder therapy nervous system regeneration nonhuman therapy evaluation spinal cord injury stem cell transplantation therapy design /development

项目摘要

DESCRIPTION (provided by applicant): Bone marrow stromal cells (MSC) have shown great promise in improving outcome after spinal cord injury. There is, however, no efficient method to deliver them to the injury site. This is a small and focused research proposal that aims to develop and optimize protocols for delivering MSC via a Lumbar Puncture (LP) in a rat model of spinal contusion. LP delivery of MSC is a minimally invasive procedure that can be easily translated into human patients. Delivery of MSC via LP places cells into the cerebrospinal fluid (CSF), away from the hostile environment of the contused cord, and yet the circulating CSF offers MSC an opportunity to home into the injured site. Preliminary data and our published experience demonstrates that LP delivery is a feasible proposition. First, this project proposes to determine optimal protocols for performing LP transplantation of MSC for spinal cord contusion. Next, it uses these optimal protocols and compares their functional outcome with the standard method of direct parenchymal transplantation. Finally, it explores the possibility of performing autologous MSC transplantation (using syngeneic transplantation to mimic the autologous model) without any immunosuppression. Long-term cell survival experiments are also proposed to demonstrate lack of neoplastic potential and other toxicities with MSC transplantation into the central nervous system. All protocols will be validated by performing detailed histological and behavioral assessments. It is hoped that the results generated from this project will produce an innovative methodology for delivering stem cells in a minimally invasive way. This novel technique will lead to significant breakthroughs in translating basic stem cell research into the clinic and will facilitate earlier clinical trials because of the minimally invasive nature of this technique.

描述（由申请人提供）：骨髓基质细胞（MSC）在改善脊髓损伤后的预后表现出了巨大的希望。但是，没有有效的方法将其运送到伤害部位。这是一项小型且重点的研究建议，旨在通过脊柱挫伤大鼠模型中的腰椎穿刺（LP）来开发和优化用于提供MSC的方案。 MSC的LP递送是一种微创手术，可以轻松地转化为人类患者。通过LP传递MSC，将细胞置于脑脊液（CSF），远离挫折绳索的敌对环境，但循环的CSF为MSC提供了一个机会，可以回家进入受伤部位。初步数据和我们已发表的经验表明，LP交付是一个可行的主张。首先，该项目建议确定对MSC进行LP移植的最佳方案。接下来，它使用这些最佳协议，并将其功能结果与直接实质移植的标准方法进行比较。最后，它探讨了执行自体MSC移植（使用合成性移植以模仿自体模型）的可能性，而无需任何免疫抑制。还提出了长期的细胞存活实验，以证明缺乏肿瘤潜力和其他毒性，并将MSC移植到中枢神经系统中。所有协议将通过执行详细的组织学和行为评估来验证。希望该项目产生的结果将产生一种创新的方法，用于以微创的方式传递干细胞。这项新型技术将导致将基本干细胞研究转化为诊所的重大突破，并且由于该技术的微创性质，将促进早期的临床试验。