title: PEDF and VEGF-A output from human retinal pigment epithelial cells grown on novel microcarriers.
abstract: Human retinal pigment epithelial (hRPE) cells have been tested as a cell-based therapy for Parkinson's disease but will require additional study before further clinical trials can be planned. We now show that the long-term survival and neurotrophic potential of hRPE cells can be enhanced by the use of FDA-approved plastic-based microcarriers compared to a gelatin-based microcarrier as used in failed clinical trials. The hRPE cells grown on these plastic-based microcarriers display several important characteristics of hRPE found in vivo: (1) characteristic morphological features, (2) accumulation of melanin pigment, and (3) high levels of production of the neurotrophic factors pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A). Growth of hRPE cells on plastic-based microcarriers led to sustained levels (>1 ng/ml) of PEDF and VEGF-A in conditioned media for two months. We also show that the expression of VEGF-A and PEDF is reciprocally regulated by activation of the GPR143 pathway. GPR143 is activated by L-DOPA (1 μM) which decreased VEGF-A secretion as opposed to the previously reported increase in PEDF secretion. The hRPE microcarriers are therefore novel candidate delivery systems for achieving long-term delivery of the neuroprotective factors PEDF and VEGF-A, which could have a value in neurodegenerative conditions such as Parkinson's disease.
authors.affiliation: Department of Neurology, College of Medicine, The University of Arizona, AHSC, P.O. Box 245023, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA. tfalk@u.arizona.edu
authors.forename: Torsten
authors.initials: T
authors.lastname: Falk
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Congrove
authors.forename: Shiling
authors.initials: S
authors.lastname: Zhang
authors.forename: Alexander D
authors.initials: AD
authors.lastname: McCourt
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Sherman
authors.forename: Brian S
authors.initials: BS
authors.lastname: McKay
mesh_terms: D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002478:Cells, Cultured; D005136:Eye Proteins / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D010784:Photomicrography; D010969:Plastics; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007980:Levodopa; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D010969:Plastics; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C095276:GPR143 protein, human; C467484:VEGFA protein, human