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

J Biomed Biotechnol. 2012;2012:278932. doi: 10.1155/2012/278932. Epub 2012 Apr 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / instrumentation*
  • Cell Culture Techniques / methods
  • Cells, Cultured
  • Eye Proteins / metabolism*
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Humans
  • Levodopa / metabolism
  • Membrane Glycoproteins / metabolism
  • Nerve Growth Factors / metabolism*
  • Photomicrography
  • Plastics
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism*
  • Serpins / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Eye Proteins
  • GPR143 protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Nerve Growth Factors
  • Plastics
  • Serpins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor
  • Levodopa