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

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 c...

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Main Authors: Richard J. Davis, Nazia M. Alam, Cuiping Zhao, Claudia Müller, Janmeet S. Saini, Timothy A. Blenkinsop, Francesca Mazzoni, Melissa Campbell, Susan M. Borden, Carol J. Charniga, Patty L. Lederman, Vanessa Aguilar, Michael Naimark, Michael Fiske, Nathan Boles, Sally Temple, Silvia C. Finnemann, Glen T. Prusky, Jeffrey H. Stern
Format: Article
Language:English
Published: Elsevier 2017-07-01
Series:Stem Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117302230
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author Richard J. Davis
Nazia M. Alam
Cuiping Zhao
Claudia Müller
Janmeet S. Saini
Timothy A. Blenkinsop
Francesca Mazzoni
Melissa Campbell
Susan M. Borden
Carol J. Charniga
Patty L. Lederman
Vanessa Aguilar
Michael Naimark
Michael Fiske
Nathan Boles
Sally Temple
Silvia C. Finnemann
Glen T. Prusky
Jeffrey H. Stern
author_facet Richard J. Davis
Nazia M. Alam
Cuiping Zhao
Claudia Müller
Janmeet S. Saini
Timothy A. Blenkinsop
Francesca Mazzoni
Melissa Campbell
Susan M. Borden
Carol J. Charniga
Patty L. Lederman
Vanessa Aguilar
Michael Naimark
Michael Fiske
Nathan Boles
Sally Temple
Silvia C. Finnemann
Glen T. Prusky
Jeffrey H. Stern
author_sort Richard J. Davis
collection DOAJ
description 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.
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spelling doaj.art-2f04f00793cb4317b5d4af57e00a3b052022-12-22T02:42:38ZengElsevierStem Cell Reports2213-67112017-07-0191424910.1016/j.stemcr.2017.05.016The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision RescueRichard J. Davis0Nazia M. Alam1Cuiping Zhao2Claudia Müller3Janmeet S. Saini4Timothy A. Blenkinsop5Francesca Mazzoni6Melissa Campbell7Susan M. Borden8Carol J. Charniga9Patty L. Lederman10Vanessa Aguilar11Michael Naimark12Michael Fiske13Nathan Boles14Sally Temple15Silvia C. Finnemann16Glen T. Prusky17Jeffrey H. Stern18Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USADepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10605, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USADepartment of Biological Sciences, Center for Cancer, Genetic Diseases and Gene Regulation, Fordham University, Bronx, NY 10458, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USACell, Developmental & Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Biological Sciences, Center for Cancer, Genetic Diseases and Gene Regulation, Fordham University, Bronx, NY 10458, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USAUpstate Stem Cell cGMP Facility, University of Rochester Medical Center, Rochester, NY 14642, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USADepartment of Biological Sciences, Center for Cancer, Genetic Diseases and Gene Regulation, Fordham University, Bronx, NY 10458, USADepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10605, USANeural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USAAge-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.http://www.sciencedirect.com/science/article/pii/S2213671117302230retinal pigment epitheliumRPEstem celltransplantdifferentiation stagemacular degenerationAMDdevelopmental stagevision rescueRPE transplant efficacy
spellingShingle Richard J. Davis
Nazia M. Alam
Cuiping Zhao
Claudia Müller
Janmeet S. Saini
Timothy A. Blenkinsop
Francesca Mazzoni
Melissa Campbell
Susan M. Borden
Carol J. Charniga
Patty L. Lederman
Vanessa Aguilar
Michael Naimark
Michael Fiske
Nathan Boles
Sally Temple
Silvia C. Finnemann
Glen T. Prusky
Jeffrey H. Stern
The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue
Stem Cell Reports
retinal pigment epithelium
RPE
stem cell
transplant
differentiation stage
macular degeneration
AMD
developmental stage
vision rescue
RPE transplant efficacy
title The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue
title_full The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue
title_fullStr The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue
title_full_unstemmed The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue
title_short The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue
title_sort developmental stage of adult human stem cell derived retinal pigment epithelium cells influences transplant efficacy for vision rescue
topic retinal pigment epithelium
RPE
stem cell
transplant
differentiation stage
macular degeneration
AMD
developmental stage
vision rescue
RPE transplant efficacy
url http://www.sciencedirect.com/science/article/pii/S2213671117302230
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