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The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue.
Stem Cell Reports. 2017 07 11; 9(1):42-49.SC

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.

Authors+Show Affiliations

Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.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.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Department of Biological Sciences, Center for Cancer, Genetic Diseases and Gene Regulation, Fordham University, Bronx, NY 10458, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Cell, Developmental & Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Department of Biological Sciences, Center for Cancer, Genetic Diseases and Gene Regulation, Fordham University, Bronx, NY 10458, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Upstate Stem Cell cGMP Facility, University of Rochester Medical Center, Rochester, NY 14642, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA.Department of Biological Sciences, Center for Cancer, Genetic Diseases and Gene Regulation, Fordham University, Bronx, NY 10458, USA.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.Neural Stem Cell Institute, Regenerative Research Foundation, One Discovery Drive, Rensselaer, NY 12144, USA. Electronic address: jeffreystern@neuralsci.org.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28625537

Citation

Davis, Richard J., et al. "The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue." Stem Cell Reports, vol. 9, no. 1, 2017, pp. 42-49.
Davis RJ, Alam NM, Zhao C, et al. The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. Stem Cell Reports. 2017;9(1):42-49.
Davis, R. J., Alam, N. M., Zhao, C., Müller, C., Saini, J. S., Blenkinsop, T. A., Mazzoni, F., Campbell, M., Borden, S. M., Charniga, C. J., Lederman, P. L., Aguilar, V., Naimark, M., Fiske, M., Boles, N., Temple, S., Finnemann, S. C., Prusky, G. T., & Stern, J. H. (2017). The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. Stem Cell Reports, 9(1), 42-49. https://doi.org/10.1016/j.stemcr.2017.05.016
Davis RJ, et al. The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. Stem Cell Reports. 2017 07 11;9(1):42-49. PubMed PMID: 28625537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. AU - Davis,Richard J, AU - Alam,Nazia M, AU - Zhao,Cuiping, AU - Müller,Claudia, AU - Saini,Janmeet S, AU - Blenkinsop,Timothy A, AU - Mazzoni,Francesca, AU - Campbell,Melissa, AU - Borden,Susan M, AU - Charniga,Carol J, AU - Lederman,Patty L, AU - Aguilar,Vanessa, AU - Naimark,Michael, AU - Fiske,Michael, AU - Boles,Nathan, AU - Temple,Sally, AU - Finnemann,Silvia C, AU - Prusky,Glen T, AU - Stern,Jeffrey H, Y1 - 2017/06/15/ PY - 2016/11/28/received PY - 2017/05/15/revised PY - 2017/05/15/accepted PY - 2017/6/20/pubmed PY - 2018/5/1/medline PY - 2017/6/20/entrez KW - AMD KW - RPE KW - RPE transplant efficacy KW - developmental stage KW - differentiation stage KW - macular degeneration KW - retinal pigment epithelium KW - stem cell KW - transplant KW - vision rescue SP - 42 EP - 49 JF - Stem cell reports JO - Stem Cell Reports VL - 9 IS - 1 N2 - 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. SN - 2213-6711 UR - https://www.unboundmedicine.com/medline/citation/28625537/The_Developmental_Stage_of_Adult_Human_Stem_Cell_Derived_Retinal_Pigment_Epithelium_Cells_Influences_Transplant_Efficacy_for_Vision_Rescue_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-6711(17)30223-0 DB - PRIME DP - Unbound Medicine ER -