CHROMAFFIN CELL TRANSPLANTS AND TROPHIC FACTORS

嗜铬细胞移植和营养因子

• 批准号: 3738133
• 负责人: LARS OLSON
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3738133
• 关键词: Parkinson's disease; adrenal transplantation; autologous transplantation; axon; basal ganglia; caudate nucleus; chromaffin cells; confocal scanning microscopy; cryopreservation; dendrites; disease /disorder model; dopamine agonists; electrophysiology; fibroblast growth factor; growth factor; histocompatibility; homologous transplantation; human genetic material tag; human subject; laboratory rat; nervous system transplantation; neurogenesis; neuronal guidance; neurotrophic factors; nucleic acid hybridization; peripheral nervous system; subtraction hybridization; therapy; tissue /cell culture; tissue /organ preservation; transfection; transplantation immunology; xenotransplantation

Dr. Olson and his colleagues will carry out a series of studies on transplantation of chromaffin cells into rat animal models of Parkinsons disease and into human suffering from this illness. In experiments involving chromaffin cell rat allografts and human xenografts, transplanted to basal ganglia targets in rats, a number of parameters will be examined - (1) donor age, (2) type of transplantation technique used, (3) host animal immune status and endocrine state, and (4) influence of chronic dopamine agonist exposure. A major emphasis will be placed on attempts to augment survival and neurite outgrowth from chromaffin cell grafts to rats by use of trophic factors. Experimental approaches to this problem will include: (1) cografting chromaffin cells with peripheral nerve minces, (2) exposure of chromaffin cell grafts to nerve growth factor and fibroblast growth factor via immersion and perfusion techniques both before and after transplantation, and (3) genetically modifying various established cells lines and primary cell cultures to synthesize and secrete nerve growth factor and fibroblast growth factor. Such genetically modified cells would be subsequently cografted with chromaffin cells, or with fetal CNS neurons in subproject 24. In addition, subtraction hybridization will be utilized to identify hitherto unknown trophic factors for dopamine neurons. Autologous chromaffin cell grafts will also be carried out in patients suffering from Parkinsons disease. In order to improve the poor long-term efficacy of such grafts reported by ourselves and others, grafts will be exposed to nerve growth factor before and after transplantation. As the work on genetic modification of cell lines proceeds, co-transplantation of those cells and chromaffin cells may be possible in man after appropriate studies of safety and efficacy.

奥尔森博士和他的同事将进行一系列的研究， 嗜铬细胞移植治疗帕金森病的实验研究 疾病和人类遭受这种疾病的痛苦。 在实验中 涉及嗜铬细胞大鼠同种异体移植物和人异种移植物，移植 对于大鼠基底神经节靶点，将检查许多参数- (1)供体年龄，（2）移植技术类型，（3）宿主动物 免疫状态和内分泌状态;（4）慢性多巴胺影响 激动剂暴露。 一个主要的重点将放在试图增加生存和神经突 通过使用营养因子从嗜铬细胞移植到大鼠的生长。 解决这一问题的实验方法包括：（1）共移植 嗜铬细胞伴周围神经损伤;（2）嗜铬细胞暴露 细胞移植到神经生长因子和成纤维细胞生长因子， 移植前后的浸泡和灌注技术， 和（3）遗传修饰各种已建立的细胞系和原代 合成和分泌神经生长因子和成纤维细胞的细胞培养物 生长因子 这种基因修饰的细胞随后将被 与嗜铬细胞或胎儿CNS神经元共移植 24. 此外，还将利用扣除杂交来鉴定 迄今未知的多巴胺神经元营养因子。 自体嗜铬细胞移植也将在患者中进行 患有帕金森病。 为了改善穷人的长期 我们和其他人报道的这种移植物的疗效，移植物将是 在移植前后暴露于神经生长因子。 为 细胞系的遗传修饰工作继续进行， 这些细胞和嗜铬细胞可能在人类适当的 安全性和有效性的研究。