Characterization and Survival of Long-Term Implants of Human Retinal Pigment Epithelial Cells Attached to Gelatin Microcarriers in a Model of Parkinson Disease

Previous studies have demonstrated that the intrastriatal implantation of human retinal pigment epithelial cells attached to gelatin microcarriers (hRPE-GM) ameliorates behavioral deficits in animal models of Parkinson disease. However, there are only sparse data on cell survival in the host. In thi...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2007-07, Vol.66 (7), p.585-596
Main Authors: Flores, Joseph, Cepeda, Ivan L, Cornfeldt, Michael L, O'Kusky, John R, Doudet, Doris J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Survival
Cell Transplantation - methods
Corpus Striatum - pathology
Corpus Striatum - physiopathology
Corpus Striatum - surgery
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Gelatin - therapeutic use
Humans
Male
Medical sciences
Microscopy, Electron, Transmission - methods
Microspheres
Nerve Tissue Proteins - metabolism
Neurology
Parkinson Disease - etiology
Parkinson Disease - physiopathology
Parkinson Disease - surgery
Pigment Epithelium of Eye - physiology
Pigment Epithelium of Eye - transplantation
Pigment Epithelium of Eye - ultrastructure
Rats
Rats, Sprague-Dawley
Time Factors
Transplantation, Heterologous - methods
Tumors of the nervous system. Phacomatoses
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Summary:Previous studies have demonstrated that the intrastriatal implantation of human retinal pigment epithelial cells attached to gelatin microcarriers (hRPE-GM) ameliorates behavioral deficits in animal models of Parkinson disease. However, there are only sparse data on cell survival in the host. In this study, we characterized a variety of retinal pigment epithelial (RPE)-specific markers in vitro and used these markers to investigate the long-term survival of hRPE-GM implants. Sprague-Dawley rats (n = 22) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and implanted with hRPE-GM without immunosuppression. Rats were euthanized at 48 hours, 7 days, 4 weeks, and 5 months postimplant and immunohistochemically processed using the following antibodies1) human-specific nuclear mitotic apparatus protein (NuMA-Ab2), 2) epithelial-specific extracellular matrix metalloproteinase inducer (EMMPRIN), 3) RPE cell-specific RPE65, and the inflammation markers 4) glial fibrillary acidic protein and 5) ED1 (rat CD68). Our analysis revealed NuMA-, EMMPRIN-, and RPE65-immunoreactive cells at different times postimplant. The morphologic features of hRPE cell implants (at 48 hours and 5 months) were confirmed by electron microscopy. Furthermore, despite evidence of chronic inflammation at the later time point, there is an appreciable number of surviving hRPE cells. This study suggests that hRPE-GM implants can survive in the absence of immunosuppression and can be potentially used as an alternative for treating Parkinson disease.
ISSN:0022-3069
1554-6578
DOI:10.1097/nen.0b013e318093e53a