Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells§

Authors

  • David E. Buchholz,

    1. Center for Stem Cell Biology and Engineering,University of California, Santa Barbara, California, USA
    2. Neuroscience Research Institute,University of California, Santa Barbara, California, USA
    3. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California, USA
    Search for more papers by this author
  • Sherry T. Hikita,

    1. Center for Stem Cell Biology and Engineering,University of California, Santa Barbara, California, USA
    2. Neuroscience Research Institute,University of California, Santa Barbara, California, USA
    3. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California, USA
    Search for more papers by this author
  • Teisha J. Rowland,

    1. Center for Stem Cell Biology and Engineering,University of California, Santa Barbara, California, USA
    2. Neuroscience Research Institute,University of California, Santa Barbara, California, USA
    3. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California, USA
    Search for more papers by this author
  • Amy M. Friedrich,

    1. Center for Stem Cell Biology and Engineering,University of California, Santa Barbara, California, USA
    2. Neuroscience Research Institute,University of California, Santa Barbara, California, USA
    3. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California, USA
    Search for more papers by this author
  • Cassidy R. Hinman,

    1. Center for Stem Cell Biology and Engineering,University of California, Santa Barbara, California, USA
    2. Neuroscience Research Institute,University of California, Santa Barbara, California, USA
    3. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California, USA
    Search for more papers by this author
  • Lincoln V. Johnson,

    1. Center for Stem Cell Biology and Engineering,University of California, Santa Barbara, California, USA
    2. Center for the Study of Macular Degeneration,University of California, Santa Barbara, California, USA
    3. Neuroscience Research Institute,University of California, Santa Barbara, California, USA
    4. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California, USA
    Search for more papers by this author
  • Dennis O. Clegg

    Corresponding author
    1. Center for Stem Cell Biology and Engineering,University of California, Santa Barbara, California, USA
    2. Center for the Study of Macular Degeneration,University of California, Santa Barbara, California, USA
    3. Neuroscience Research Institute,University of California, Santa Barbara, California, USA
    4. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California, USA
    • Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA
    Search for more papers by this author
    • Telephone: 805-893-8490; Fax: 805-893-2005


  • Author contributions: D.E.B.: Conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; S.T.H.: Conception and design, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; T.J.R.: Conception and design, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; A.M.F.: Collection and/or assembly of data, final approval of manuscript; C.R.H.: Collection and/or assembly of data, final approval of manuscript; L.V.J.: Conception and design, financial support, final approval of manuscript; D.O.C.: Conception and design, financial support, final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS August 5, 2009.

Abstract

Human induced pluripotent stem cells (iPSCs) have great promise for cellular therapy, but it is unclear if they have the same potential as human embryonic stem cells (hESCs) to differentiate into specialized cell types. Ocular cells such as the retinal pigmented epithelium (RPE) are of particular interest because they could be used to treat degenerative eye diseases, including age-related macular degeneration and retinitis pigmentosa. We show here that iPSCs generated using Oct4, Sox2, Nanog, and Lin28 can spontaneously differentiate into RPE cells, which can then be isolated and cultured to form highly differentiated RPE monolayers. RPE derived from iPSCs (iPS-RPE) were analyzed with respect to gene expression, protein expression, and rod outer segment phagocytosis, and compared with cultured fetal human RPE (fRPE) and RPE derived from hESCs (hESC-RPE). iPS-RPE expression of marker mRNAs was quantitatively similar to that of fRPE and hESC-RPE, and marker proteins were appropriately expressed and localized in polarized monolayers. Levels of rod outer segment phagocytosis by iPS-RPE, fRPE, and hESC-RPE were likewise similar and dependent on integrin αvβ5. This work shows that iPSCs can differentiate into functional RPE that are quantitatively similar to fRPE and hESC-RPE and further supports the finding that iPSCs are similar to hESCs in their differentiation potential. STEM CELLS 2009;27:2427–2434

Ancillary