PEDF and VEGF-A output from human retinal pigment epithelial cells grown on novel microcarriers

Torsten Falk, Nicole R. Congrove, Shiling Zhang, Alexander D. McCourt, Scott J Sherman, Brian S Mckay

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (1ng/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 (1M) 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.

Original languageEnglish (US)
Article number278932
JournalJournal of Biomedicine and Biotechnology
Volume2012
DOIs
StatePublished - 2012

Fingerprint

Retinal Pigments
Vascular Endothelial Growth Factor A
Epithelial Cells
Plastics
Parkinson Disease
Clinical Trials
Melanins
Nerve Growth Factors
Gelatin
Conditioned Culture Medium
Cell- and Tissue-Based Therapy
Pigments
pigment epithelium-derived factor
Chemical activation
Survival
Growth

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

PEDF and VEGF-A output from human retinal pigment epithelial cells grown on novel microcarriers. / Falk, Torsten; Congrove, Nicole R.; Zhang, Shiling; McCourt, Alexander D.; Sherman, Scott J; Mckay, Brian S.

In: Journal of Biomedicine and Biotechnology, Vol. 2012, 278932, 2012.

Research output: Contribution to journalArticle

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