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...
Main Authors: | , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2017-07-01
|
Series: | Stem Cell Reports |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117302230 |
_version_ | 1828306842852261888 |
---|---|
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. |
first_indexed | 2024-04-13T14:49:32Z |
format | Article |
id | doaj.art-2f04f00793cb4317b5d4af57e00a3b05 |
institution | Directory Open Access Journal |
issn | 2213-6711 |
language | English |
last_indexed | 2024-04-13T14:49:32Z |
publishDate | 2017-07-01 |
publisher | Elsevier |
record_format | Article |
series | Stem Cell Reports |
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 |
work_keys_str_mv | AT richardjdavis thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT naziamalam thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT cuipingzhao thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT claudiamuller thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT janmeetssaini thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT timothyablenkinsop thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT francescamazzoni thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT melissacampbell thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT susanmborden thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT caroljcharniga thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT pattyllederman thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT vanessaaguilar thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT michaelnaimark thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT michaelfiske thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT nathanboles thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT sallytemple thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT silviacfinnemann thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT glentprusky thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT jeffreyhstern thedevelopmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT richardjdavis developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT naziamalam developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT cuipingzhao developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT claudiamuller developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT janmeetssaini developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT timothyablenkinsop developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT francescamazzoni developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT melissacampbell developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT susanmborden developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT caroljcharniga developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT pattyllederman developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT vanessaaguilar developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT michaelnaimark developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT michaelfiske developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT nathanboles developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT sallytemple developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT silviacfinnemann developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT glentprusky developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue AT jeffreyhstern developmentalstageofadulthumanstemcellderivedretinalpigmentepitheliumcellsinfluencestransplantefficacyforvisionrescue |