Sertoli Cell Co-transplants in Parkinson's Disease

支持细胞是起源于睾丸的有丝分裂后细胞。它们表达和分泌许多营养、营养和调节蛋白，能够为发育中的生殖细胞提供营养和免疫支持。这些特性使它们成为传统神经移植治疗帕金森病等神经退行性疾病的理想细胞候选者。这是一种新的治疗方法，通过营养和免疫支持可以增加移植神经元的存活，减少对免疫抑制剂长期治疗的需要。本I期研究计划拟通过体外筛选试验确定最有效细胞的来源，通过完成彻底的体内剂量-反应关系来确定产生最佳神经元存活的支持细胞与神经元的比例，并确定这些细胞在跨物种移植时是否继续提供免疫保护。这些研究在帕金森病动物模型中的成功对于这些细胞作为移植物促进剂或作为其他神经退行性疾病长期局部输送营养鸡尾酒的载体的治疗潜力具有重要意义。建议的商业应用：神经移植有可能逆转PD、运动神经元病、中风等疾病的进行性退行性变。然而，神经元存活率很低，宿主对移植细胞产生的免疫反应可能进一步破坏移植物。支持细胞提供了一种新的、自然产生的技术来提高神经元的存活率，提供局部免疫抑制，而不存在长期全身抑制的健康风险，并可能减少疾病症状，超出目前可达到的水平。

Sertoli cells are post-mitotic cells originating in the testes. They express and secrete many trophic, nutritive and regulatory proteins that are able to provide trophic and immunologic support for the developing germ cell. These characteristics make them an ideal cell candidate for an adjunct to traditional neural transplantation for neurodegenerative diseases such as Parkinson's disease. This is a novel therapeutic approach that through trophic and immune support could increase the survival of transplanted neurons and decrease the need for long-term treatment with immunosuppressants. This Phase I research program proposes to determine the source of the most efficacious cells using in vitro screening assays, determine the Sertoli to neuron ratio that produces optimal neuronal survival through completion of a thorough in vivo dose-response relationship, and determine whether these cells continue to provide immune protection when grafted across species. The success of these studies in an animal model of Parkinson's disease has important implications for the therapeutic potential of these cells as graft facilitators or as the vehicle for long-term local delivery of a trophic cocktail in other neurodegenerative diseases. PROPOSED COMMERCIAL APPLICATIONS: Neural transplantation has the potential to reverse progressive degeneration in diseases such as PD, Motor Neuron Disease, Stroke. However, neuronal survival is poor and a host-generated immune response to the transplanted cells may further destroy the graft. Sertoli cells provide a novel, naturally-occurring technology to enhance neuronal survival, provide localized immunosuppression without the health risks of long-term systemic suppression and possibly decrease disease symptoms beyond currently attainable levels.