Sertoli Cell Co-transplants in Parkinson's Disease

支持细胞联合移植治疗帕金森病

• 批准号: 6337127
• 负责人: ALISON E WILLING
• 金额: $ 17.61万
• 依托单位: SANERON CCEL THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6337127
• 关键词: Parkinson's disease; Sertoli cells; cell population study; cell transplantation; dopamine; immunocytochemistry; immunosuppression; laboratory mouse; laboratory rat; lymphocyte proliferation; nervous system transplantation; neurotrophic factors; swine; technology /technique development; tissue /cell culture

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.

Sertoli细胞是源自睾丸的有丝分裂细胞。他们表达并分泌许多营养，营养和调节性蛋白质，它们能够为发育中的生殖细胞提供营养和免疫学支持。 这些特征使它们成为传统神经移植辅助神经退行性疾病（如帕金森氏病）的理想细胞候选者。这是一种新型的治疗方法，通过营养和免疫支持可以增加移植神经元的存活，并减少对免疫抑制剂长期治疗的需求。该阶段I研究计划建议使用体外筛选测定法确定最有效细胞的来源，确定通过完成彻底的体内剂量反应关系，确定可产生最佳神经元存活的Sertoli与神经元比，并确定这些细胞在跨物种植入物种时是否继续提供免疫保护。这些研究在帕金森氏病动物模型中的成功对这些细胞作为移植物促进剂的治疗潜力或作为其他神经退行性疾病中营养鸡尾酒长期递送的载体具有重要意义。拟议的商业应用：神经移植有可能在PD，运动神经元疾病，中风等疾病中逆向进行性变性。然而，神经元存活较差，宿主对移植细胞的免疫反应可能会进一步破坏移植物。 Sertoli细胞提供了一种新型的，自然的技术来增强神经元存活，提供局部免疫抑制，而没有长期全身抑制的健康风险，并可能降低疾病症状，超出目前可达到的水平。

项目成果

Enhancing tyrosine hydroxylase expression and survival of fetal ventral mesencephalon neurons with rat or porcine Sertoli cells in vitro.

在体外用大鼠或猪支持细胞增强胎儿腹侧中脑神经元的酪氨酸羟化酶表达和存活。

• DOI: 10.1016/j.brainres.2006.04.058
• 发表时间: 2006
• 期刊: Brain research.
• 作者: Shamekh,Rania;Mallery,Jennifer;Newcomb,Jennifer;Hushen,Joelle;Saporta,Samuel;Cameron,DonF;Sanberg,CyndyDavis;Sanberg,PaulR;Willing,AlisonE
• 通讯作者: Willing,AlisonE

Survival of rat or mouse ventral mesencephalon neurons after cotransplantation with rat sertoli cells in the mouse striatum.

与小鼠纹状体中的大鼠支持细胞共移植后，大鼠或小鼠腹侧中脑神经元的存活。

• DOI: 10.3727/000000005783982747
• 发表时间: 2005
• 期刊: Cell transplantation
• 影响因子: 3.3
• 作者: Shamekh,R;Newcomb,J;Mallery,J;Cassady,CJ;Saporta,S;Cameron,DF;Sanberg,PR;Willing,AE
• 通讯作者: Willing,AE