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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027694-02
Application #
3414085
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1988-12-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
Schools of Earth Sciences/Natur
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Aebischer, P; Goddard, M; Signore, A P et al. (1994) Functional recovery in hemiparkinsonian primates transplanted with polymer-encapsulated PC12 cells. Exp Neurol 126:151-8
Jaeger, C B; Aebischer, P; Tresco, P A et al. (1992) Growth of tumour cell lines in polymer capsules: ultrastructure of encapsulated PC12 cells. J Neurocytol 21:469-80
Tresco, P A; Winn, S R; Tan, S et al. (1992) Polymer-encapsulated PC12 cells: long-term survival and associated reduction in lesion-induced rotational behavior. Cell Transplant 1:255-64
Jaeger, C B; Winn, S R; Tresco, P A et al. (1991) Repair of the blood-brain barrier following implantation of polymer capsules. Brain Res 551:163-70
Winn, S R; Tresco, P A; Zielinski, B et al. (1991) Behavioral recovery following intrastriatal implantation of microencapsulated PC12 cells. Exp Neurol 113:322-9
Kraig, R P; Dong, L M; Thisted, R et al. (1991) Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein. J Neurosci 11:2187-98
Aebischer, P; Winn, S R; Tresco, P A et al. (1991) Transplantation of polymer encapsulated neurotransmitter secreting cells: effect of the encapsulation technique. J Biomech Eng 113:178-83
Aebischer, P; Tresco, P A; Winn, S R et al. (1991) Long-term cross-species brain transplantation of a polymer-encapsulated dopamine-secreting cell line. Exp Neurol 111:269-75
Jaeger, C B; Greene, L A; Tresco, P A et al. (1990) Polymer encapsulated dopaminergic cell lines as ""alternative neural grafts"". Prog Brain Res 82:41-6
Kraig, R P; Jaeger, C B (1990) Ionic concomitants of astroglial transformation to reactive species. Stroke 21:III184-7