HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Data Supplement All Versions of this Article: WNL.0b013e3181bbff1cv1 73/14/1095    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Farag, E. S. Articles by Bronstein, J. PubMed PubMed Citation Articles by Farag, E. S. Articles by Bronstein, J. Related Collections Parkinson's disease/Parkinsonism Related Article

Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease

From the UCLA Department of Neurology (E.S.F., H.V.V., J.B.); WLA VA Southwest PADRECC (E.S.F., J.B.), Los Angeles; and UCLA Section of Neuropathology (H.V.V.), Department of Pathology and Laboratory Medicine, Los Angeles, CA.

Address correspondence and reprint requests to Dr. Emad Farag, Movement Disorders Program, UCLA Department of Neurology, 300 UCLA Medical Plaza Ste. B200, Los Angeles, CA 90095 efarag{at}mednet.ucla.edu.

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 -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.

Abbreviations: 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.

Supplemental data at www.neurology.org

Editorial, page 1086.

e-Pub ahead of print on September 2, 2009, at www.neurology.org.

Disclosure: Author disclosures are provided at the end of the article.

Received March 20, 2009. Accepted in final form July 27, 2009.

Related Article

Autopsy investigation of neurodegenerative disease transplant patients: Hindsight is 20/20

James F. Morley and John E. Duda
Neurology 2009 73: 1086-1087. [Full Text] [PDF]

This article has been cited by other articles:

				J. F. Morley and J. E. Duda Autopsy investigation of neurodegenerative disease transplant patients: Hindsight is 20/20 Neurology, October 6, 2009; 73(14): 1086 - 1087. [Full Text] [PDF]