Percutaneous delivery of stem cells for spinal cord injury

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方面显示出巨大的希望。然而，没有有效的方法将它们运送到受伤部位。这是一项小型的重点研究计划，旨在开发和优化通过腰椎穿刺（LP）在大鼠脊髓挫伤模型中输送MSC的方案。骨髓间充质干细胞的LP输送是一种微创手术，可以很容易地转化为人类患者。通过LP输送间充质干细胞可使细胞进入脑脊液（CSF），远离受损脊髓的恶劣环境，而循环的CSF又为间充质干细胞提供了进入受伤部位的机会。初步数据和我们发表的经验表明，LP交付是一个可行的提议。首先，本项目提出确定骨髓间充质干细胞LP移植治疗脊髓挫伤的最佳方案。接下来，它使用这些最佳方案，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，它探讨了在没有任何免疫抑制的情况下进行自体间充质干细胞移植（使用同基因移植来模仿自体模型）的可能性。长期细胞存活实验也被提出，以证明MSC移植到中枢神经系统缺乏肿瘤潜能和其他毒性。所有方案将通过详细的组织学和行为评估进行验证。希望从这个项目中产生的结果将产生一种以微创方式输送干细胞的创新方法。这项新技术将在将基础干细胞研究转化为临床方面取得重大突破，并将促进早期临床试验，因为这项技术的微创性。

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.