ENCAPSULATED DOPAMINERGIC TUMOR CELLS AS BRAIN IMPLANTS

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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.