Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease.
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.
Farag
Emad S
ES
Movement Disorders Program, UCLA Department of Neurology, 300 UCLA Medical Plaza Ste. B200, Los Angeles, CA 90095, USA. efarag@mednet.ucla.edu
Vinters
Harry V
HV
Bronstein
Jeff
J
D000368:Aged; D001344:Autopsy; D002452:Cell Count; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D004847:Epithelial Cells / Q000637:transplantation; D005911:Gliosis / Q000209:etiology; D006085:Graft Survival; D006416:Hematoxylin; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016631:Lewy Bodies / Q000737:chemistry / Q000473:pathology; D008297:Male; D016377:Organ Transplantation; D010300:Parkinson Disease / Q000473:pathology* / Q000601:surgery*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000637:transplantation*; D011699:Putamen / Q000601:surgery*; D013238:Stereotaxic Techniques / Q000009:adverse effects; D016896:Treatment Outcome; D051844:alpha-Synuclein / Q000032:analysis
D004396:Coloring Agents; D051844:alpha-Synuclein; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin