ENCAPSULATED DOPAMINERGIC TUMOR CELLS AS BRAIN IMPLANTS

这项工作的目标是建立有效性， 包封的多巴胺能（DA）细胞系在治疗 选择性DA递质缺乏，如帕金森病。 封装提供了一个限定几何形状的屏障， 封闭的细胞和它们的目标之间的渗透性。 它 限制了细胞群的生长， 和识别，免疫保护，以及更多的控制， 植入物与宿主之间相互作用与直接 细胞团的植入。 两种DA细胞系：嗜铬细胞瘤衍生的PC 12和鼠DA细胞系 神经母细胞瘤NX 31/T28将被封装在聚氯乙烯中 丙烯酸共聚物胶囊。 这些细胞在没有突触 相互作用并合成大量多巴胺。 的 包封的细胞将进一步保持在培养物中， 置于尾壳核或苍白球区域， Sprague道利大鼠。 经过1个月到1年的时间， 胶囊或包含细胞填充的大脑区域 将胶囊固定用于组织学、切片和几何结构， 估计胶囊中活细胞的体积和数量。 在 其他动物的胶囊将被植入尾壳核 区域先前已经耗尽DA末端，具有6- 羟多巴胺（6-OHDA）。 这些植入物能够 恢复DA功能将通过使用“旋转 啮齿动物”范例。 具体目标是：（1）确定 确保PC 12长期存活的技术变量， 聚合物胶囊中的NX 31/T28细胞。 (2)为了证实 DA细胞囊对单侧6- OHDA损伤大鼠。 (3)以确定宿主的大脑和免疫系统 对植入细胞胶囊的反应。 拟议的研究将 提供关于使用寿命和稳定性的基本信息， 封装的DA细胞，多巴胺的功能有效性 释放，以及与宿主大脑的相互作用。 一个成功 拟议工作的结果可能导致更好的 了解和治疗大脑中DA缺乏症。

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.