title: Neonatal human retinal pigment epithelial cells secrete limited trophic factors in vitro and in vivo following striatal implantation in parkinsonian rats.
abstract: Human retinal pigment epithelial (hRPE) cell implants into the striatum have been investigated as a potential cell-based treatment for Parkinson's disease in a Phase II clinical trial that recently failed. We hypothesize that the trophic factor potential of the hRPE cells could potentially influence the function and/or survival of the implants and may be involved in an alternative mechanism of action. However, it is unclear if hRPE cells secreted trophic factors when handled in the manner used in the clinical Phase II trial. To address these questions, we investigated two neonatal hRPE cell lots, cultured in a similar manner to hRPE cells used in a Phase II clinical study, and longitudinally determined brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and pigment epithelium-derived factor concentrations in vitro and following striatal implantation into 6-hydroxydopamine-lesioned rats. The results demonstrate short-lived BDNF and FGF2 concentrations in vitro from hRPE cells grown alone or attached to gelatin microcarriers (GM)s as well as limited trophic factor concentration differences in vivo following striatal implantation of hRPE-GM in 6-hydroxydopamine lesioned rats compared to sham (GM-only). The data suggest that trophic factors from neonatal hRPE cell implants likely did not participate in an alternative mechanism of action, which adds supports to a hypothesis that additional factors may have been necessary for the survival and/or function of hRPE implants and potentially the success of the Phase II clinical trial.
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. kruss1@interchange.ubc.ca.|Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. kruss1@interchange.ubc.ca.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Russ
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Flores
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brudek
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
authors.forename: Doris
authors.initials: D
authors.lastname: Doudet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017322:Clinical Trials, Phase II as Topic; D003342:Corpus Striatum / Q000601:surgery*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*
chemical_list: D009414:Nerve Growth Factors
keywords: 6-Hydroxydopamine; Cell transplantation; Levodopa; Neonatal; Parkinson’s disease; Retinal pigment epithelial cells; Trophic factors