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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 α-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.
Glossary
- ABC=
- avidin-biotin-peroxidase complex;
- DAB=
- diaminobenzidine tetrahydrochloride;
- EGTA=
- ethylene glycol-bis[β-aminoethyl ether]-N,N,N′N′-tetraacetic acid;
- GFAP=
- glial fibrillary acidic protein;
- H-E=
- hematoxylin-eosin;
- PD=
- Parkinson disease;
- PEDF=
- pigment epithelial derived factor;
- RPE=
- retinal pigment epithelium.
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