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Stem Cell Reports. 2017 Jul 11;9(1):42-49. doi: 10.1016/j.stemcr.2017.05.016. Epub 2017 Jun 15.

The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue.

Author information

1
Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.
2
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10605, USA; Center for Visual Restoration, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA.
3
Department of Biological Sciences, Center for Cancer, Genetic Diseases and Gene Regulation, Fordham University, Bronx, NY 10458, USA.
4
Cell, Developmental & Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Upstate Stem Cell cGMP Facility, University of Rochester Medical Center, Rochester, NY 14642, USA.
6
Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA. Electronic address: jeffreystern@neuralsci.org.

Abstract

Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.

KEYWORDS:

AMD; RPE; RPE transplant efficacy; developmental stage; differentiation stage; macular degeneration; retinal pigment epithelium; stem cell; transplant; vision rescue

PMID:
28625537
PMCID:
PMC5511099
DOI:
10.1016/j.stemcr.2017.05.016
[Indexed for MEDLINE]
Free PMC Article

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