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前景。然而，没有有效的方法将它们递送到损伤部位。这是一个小型而集中的研究提案，旨在开发和优化通过腰椎穿刺（LP）在脊髓挫伤大鼠模型中递送MSC的方案。MSC的LP递送是一种微创手术，可以很容易地转化为人类患者。通过LP递送MSC将细胞置于脑脊液（CSF）中，远离挫伤脊髓的不利环境，而循环的CSF为MSC提供了回到受伤部位的机会。初步数据和我们发表的经验表明，LP交付是一个可行的主张。首先，本项目提出确定最佳方案进行骨髓间充质干细胞LP移植脊髓挫伤。接下来，它使用这些最佳的协议，并比较他们的功能结果与直接实质移植的标准方法。最后，它探讨了在没有任何免疫抑制的情况下进行自体MSC移植（使用同基因移植来模拟自体模型）的可能性。还提出了长期细胞存活实验来证明MSC移植到中枢神经系统中缺乏肿瘤潜力和其他毒性。将通过进行详细的组织学和行为评估来验证所有方案。希望该项目产生的结果将产生一种以微创方式提供干细胞的创新方法。这项新技术将导致将基础干细胞研究转化为临床的重大突破，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.