ENCAPSULATED DOPAMINERGIC TUMOR CELLS AS BRAIN IMPLANTS

这项工作的目标是建立 微囊化多巴胺能细胞系治疗骨肉瘤的实验研究 选择性多巴胺递质缺乏，如帕金森氏症。 封装提供了定义的几何形状的障碍，并且 封闭单元与其目标之间的渗透性。它 限制细胞数量的增长，允许精确放置 以及识别、免疫保护和对 种植体与宿主之间的相互作用与直接作用 细胞团的植入。 两种DA细胞系：嗜铬细胞瘤来源的PC12和小鼠 神经母细胞瘤NX31/T28将用聚氯乙烯包裹 丙烯酸共聚胶囊。这些细胞在没有突触的情况下存活 相互作用，合成大量的多巴胺。这个 被包裹的细胞要么在培养中进一步保持，要么 置于尾壳核或苍白球区 Spraogue Dawley大鼠。在1个月到1年的时间段后， 胶囊或包含充满细胞的大脑区域 胶囊的组织学、切片和几何形状将被固定， 估计胶囊内活细胞的体积和数量。在……里面 其他动物将把胶囊植入尾壳核 以前已耗尽6-6个DA终端的地区 羟基多巴胺(6-OHDA)。这些植入物的能力 恢复DA功能将通过以下方式进行评估 具体目标是：(1)界定 确保PC12和PC12长期生存的技术变量 在聚合物胶囊中培养NX31/T28细胞。(2)确立效力 DA细胞胶囊对单侧6-羟色胺旋转行为的影响 OHDA损毁大鼠。(3)确定宿主大脑和免疫力 对植入的细胞胶囊的反应。拟议的研究将 提供有关长寿和稳定性的基本信息 包裹的DA细胞--多巴胺的功能效应 释放，以及与宿主大脑的相互作用。一位成功的 拟议工作的结果可能会导致更好的 脑多巴胺缺乏症的认识和治疗。

The goal of this work is to establish the effectiveness of encapsulated dopaminergic (DA) cell lines in the treatment of selective DA transmitter deficiencies, such as Parkinson's Disease. Encapsulation provides a barrier of defined geometry and permeability between the enclosed cells and their target. It limits the growth of the cell population, allows precise placement and recognition, immune protection, and more control over the interaction between implant and host compared to direct implantation of the cell mass. Two DA cell lines: pheochromocytoma derived PC12 and the murine neuroblastoma NX31/T28 will be enclosed in polyvinylchloride acrylic copolymer capsules. These cells survive without synaptic interaction and synthesize large quantities of dopamine. The encapsulated cells will be either further maintained in culture or placed into the caudate-putamen or globus pallidus regions of Sprague Dawley rats. After periods of between 1 month and 1 year, the capsules or the brain regions containing the cell-filled capsules will be fixed for histology, sectioned and the geometry, volume and numbers of live cells in the capsule estimated. In other animals the capsules will be implanted into a caudate-putamen region that has been previously depleted of DA terminals with 6- hydroxydopamine (6-OHDA). The capability of these implants to restore DA function will be evaluated by using the "rotating rodent" paradigm. The specific aims are: (1) To define the technical variables that will ensure long term survival of PC12 and NX31/T28 cells in polymer capsules. (2) To establish the effects of DA cell capsules on the rotational behavior of unilaterally 6- OHDA lesioned rats. (3) To determine the host brain and immune reactions to implanted cell capsules. The proposed studies will provide basic information on the longevity and stability of the encapsulated DA cells, the functional effectiveness of dopamine release, and the interaction with the host brain. A successful outcome of the proposed work could lead to both a better understanding and treatment of DA-deficiency in the brain.