NDLI: Polarized secretion of PEDF from human embryonic stem cell-derived RPE promotes retinal progenitor cell survival.

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Polarized secretion of PEDF from human embryonic stem cell-derived RPE promotes retinal progenitor cell survival.

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Polarized secretion of PEDF from human embryonic stem cell-derived RPE promotes retinal progenitor cell survival.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Deng, Xuemei Spee, Christine Zhu, Danhong Hinton, David R. Hsieh, Chih-Lin Sonoda, Shozo Barron, Ernesto Pera, Martin
Description	Country affiliation: United States Author Affiliation: Zhu D ( Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.)
Abstract	PURPOSE: Human embryonic stem cell-derived RPE (hES-RPE) transplantation is a promising therapy for atrophic age-related macular degeneration (AMD); however, future therapeutic approaches may consider co-transplantation of hES-RPE with retinal progenitor cells (RPCs) as a replacement source for lost photoreceptors. The purpose of this study was to determine the effect of polarization of hES-RPE monolayers on their ability to promote survival of RPCs. METHODS: The hES-3 cell line was used for derivation of RPE. Polarization of hES-RPE was achieved by prolonged growth on permeable inserts. RPCs were isolated from 16- to 18-week-gestation human fetal eyes. ELISA was performed to measure pigment epithelium-derived factor (PEDF) levels from conditioned media. RESULTS: Pigmented RPE-like cells appeared as early as 4 weeks in culture and were subcultured at 8 weeks. Differentiated hES-RPE had a normal chromosomal karyotype. Phenotypically polarized hES-RPE cells showed expression of RPE-specific genes. Polarized hES-RPE showed prominent expression of PEDF in apical cytoplasm and a marked increase in secretion of PEDF into the medium compared with nonpolarized culture. RPCs grown in the presence of supernatants from polarized hES-RPE showed enhanced survival, which was ablated by the presence of anti-PEDF antibody. CONCLUSIONS: hES-3 cells can be differentiated into functionally polarized hES-RPE cells that exhibit characteristics similar to those of native RPE. On polarization, hES-RPE cells secrete high levels of PEDF that can support RPC survival. These experiments suggest that polarization of hES-RPE would be an important feature for promotion of RPC survival in future cell therapy for atrophic AMD.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.10-6413
Journal	Investigative Opthalmology & Visual Science
Issue Number	3
Volume Number	52
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2011-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Embryonic Stem Cells Cytology Metabolism Eye Proteins Nerve Growth Factors Retinal Pigment Epithelium Serpins Animals Blotting, Western Cell Culture Techniques Cell Differentiation Physiology Cell Survival Coculture Techniques Enzyme-linked Immunosorbent Assay Gene Expression Profiling Gestational Age In Situ Nick-end Labeling Karyotyping Microscopy, Confocal Phagocytosis Reverse Transcriptase Polymerase Chain Reaction Rod Cell Outer Segment Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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