CHROMAFFIN CELL TRANSPLANTS AND TROPHIC FACTORS

奥尔森博士和他的同事们将开展一系列关于 嗜铬细胞移植入帕金森病大鼠动物模型 并转化为人类遭受这种疾病的痛苦。在实验中 大鼠嗜铬细胞同种异体移植和人异种移植 对于大鼠的基底节靶点，将检测一些参数- (1)供者年龄，(2)所用移植技术类型，(3)宿主动物 免疫状态和内分泌状态，以及(4)慢性多巴胺的影响 激动剂暴露。 主要的重点将放在增加存活率和轴突的尝试上 利用营养因子从嗜铬细胞移植物向大鼠生长。 解决这一问题的实验方法包括：(1)共嫁接 嗜铬细胞伴外周神经碎屑，(2)嗜铬细胞暴露 神经生长因子和成纤维细胞生长因子的细胞移植 移植前后的浸泡和灌流技术， 以及(3)对各种已建立的细胞系和原代细胞进行遗传修饰 细胞培养合成和分泌神经生长因子和成纤维细胞 生长因子。这样的转基因细胞随后将被 与嗜铬细胞共移植，或与胎儿中枢神经元子项目 24.此外，还将利用差减杂交技术来鉴定 目前尚不清楚多巴胺神经元的营养因子。 自体嗜铬细胞移植也将在患者身上进行 患有帕金森氏症。为了长期改善贫困人口 由我们和其他人报告的此类移植物的疗效，移植物将被 移植前后应用神经生长因子。作为 细胞系基因改造的工作进展，联合移植 这些细胞和嗜铬细胞在适当的条件下在人类体内是可能的。 安全性和有效性的研究。

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.