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Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells.
Maruotti, Julien; Sripathi, Srinivas R; Bharti, Kapil; Fuller, John; Wahlin, Karl J; Ranganathan, Vinod; Sluch, Valentin M; Berlinicke, Cynthia A; Davis, Janine; Kim, Catherine; Zhao, Lijun; Wan, Jun; Qian, Jiang; Corneo, Barbara; Temple, Sally; Dubey, Ramin; Olenyuk, Bogdan Z; Bhutto, Imran; Lutty, Gerard A; Zack, Donald J.
Afiliación
  • Maruotti J; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Sripathi SR; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Bharti K; Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
  • Fuller J; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Wahlin KJ; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Ranganathan V; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Sluch VM; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Berlinicke CA; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Davis J; Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
  • Kim C; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Zhao L; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Wan J; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Qian J; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Corneo B; Stem Cell Core Facility, Columbia University, New York, NY 10032;
  • Temple S; Neural Stem Cell Institute, Rensselaer, NY 12144;
  • Dubey R; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305;
  • Olenyuk BZ; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089;
  • Bhutto I; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Lutty GA; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287;
  • Zack DJ; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287; Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, MD 21287; Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21287; Institute of Genetic Medicine, Johns Hopkins
Proc Natl Acad Sci U S A ; 112(35): 10950-5, 2015 Sep 01.
Article en En | MEDLINE | ID: mdl-26269569
Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule-only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Células Madre Pluripotentes / Epitelio Pigmentado de la Retina Tipo de estudio: Guideline / Prognostic_studies Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Células Madre Pluripotentes / Epitelio Pigmentado de la Retina Tipo de estudio: Guideline / Prognostic_studies Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos