Dataset Information

Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease.

ABSTRACT:

Background

Attempts at cell-based dopamine replacement therapy in Parkinson disease (PD) have included surgical implantation of adrenal medullary, fetal mesencephalic, and cultured human mesencephalic tissue grafts. Trials involving putamenal implantation of human retinal pigment epithelial (RPE) cells in PD have also been performed. Neuropathologic findings in humans undergoing RPE cell implantation have not heretofore been reported. We describe the brain autopsy findings from a subject enrolled in a clinical trial of RPE cells in gelatin microcarriers for treatment of PD, and suggest factors which may have impacted cell survival.

Methods

A 68-year-old man underwent bilateral surgical implantation of 325,000 RPE cells in gelatin microcarriers (Spheramine) but died 6 months after surgery. The left cerebral hemisphere was examined. Routine postmortem formalin fixation was performed and standard, as well as immunohistochemical methods used to highlight senile plaque and Lewy body pathologic changes, iron deposition, cellular inflammation, and reactive astrocytosis in implant regions. Manual cell counts were done of RPE cells.

Results

Hematoxylin-eosin and alpha-synuclein immunostains confirmed the diagnosis of PD. Needle tracts with matrix material and RPE cells were observed in the context of local inflammatory and astrocytic reactive change. A total of 118 cells were counted (estimated 0.036% survival).

Conclusions

Retinal pigment epithelial cells are seen in human brain 6 months postimplantation, but overall survival of implanted cells appeared poor.

SUBMITTER: Farag ES

PROVIDER: S-EPMC2764397 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Publications

Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease.

Farag Emad S ES Vinters Harry V HV Bronstein Jeff J

Neurology 20090902 14

<h4>Background</h4>Attempts at cell-based dopamine replacement therapy in Parkinson disease (PD) have included surgical implantation of adrenal medullary, fetal mesencephalic, and cultured human mesencephalic tissue grafts. Trials involving putamenal implantation of human retinal pigment epithelial (RPE) cells in PD have also been performed. Neuropathologic findings in humans undergoing RPE cell implantation have not heretofore been reported. We describe the brain autopsy findings from a subject ...[more]

PMID: 19726750

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Project description:Abnormal covariance pattern of regional metabolism associated with Parkinson disease (PD) is modulated by dopaminergic pharmacotherapy. Using high-resolution 18F-FDG PET and network analysis, we previously derived and validated a parkinsonism-related metabolic pattern (PRP) in nonhuman primate models of PD. It is currently not known whether this network is modulated by experimental therapeutics. In this study, we examined changes in network activity by striatal implantation of human levodopa-producing retinal pigment epithelial (hRPE) cells in parkinsonian macaques and evaluated the reproducibility of network activity in a small test-retest study.Methods18F-FDG PET scans were acquired in 8 healthy macaques and 8 macaques with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced bilateral nigrostriatal dopaminergic lesions after unilateral putaminal implantation of hRPE cells or sham surgery. PRP activity was measured prospectively in all animals and in a subset of test-retest animals using a network quantification approach. Network activity and regional metabolic values were compared on a hemispheric basis between animal groups and treatment conditions.ResultsAll individual macaques showed clinical improvement after hRPE cell implantation compared with the sham surgery. PRP activity was elevated in the untreated MPTP hemispheres relative to those of the normal controls (P < 0.00005) but was reduced (P < 0.05) in the hRPE-implanted hemispheres. The modulation observed in network activity was supported by concurrent local and remote changes in regional glucose metabolism. PRP activity remained unchanged in the untreated MPTP hemispheres versus the sham-operated hemispheres. PRP activity was also stable (P ≥ 0.29) and correlated (R2 ≥ 0.926; P < 0.00005) in the test-retest hemispheres. These findings were highly reproducible across several PRP topographies generated in multiple cohorts of parkinsonian and healthy macaques.ConclusionWe have demonstrated long-term therapeutic effects of hRPE cell implantation in nonhuman primate models of PD. The implantation of such levodopa-producing cells can concurrently decrease the elevated metabolic network activity in parkinsonian brains on an individual basis. These results parallel the analogous findings reported in patients with PD undergoing levodopa therapy and other symptomatic interventions. With further validation in large samples, 18F-FDG PET imaging with network analysis may provide a viable biomarker for assessing treatment response in animal models of PD after experimental therapies.

Dataset Information

Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease.

Background

Methods

Results

Conclusions

Publications

Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease.

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