Development of Histocompatible Primate-Induced Pluripotent Stem Cells for Neural Transplantation§

Authors

  • Michela Deleidi,

    1. Center for Neuroregeneration Research, Harvard Medical School/McLean Hospital, Belmont, Massachusetts, USA
    2. Udall Parkinson's Disease Research Center of Excellence, Boston, Massachusetts, USA
    3. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • Gunnar Hargus,

    1. Center for Neuroregeneration Research, Harvard Medical School/McLean Hospital, Belmont, Massachusetts, USA
    2. Udall Parkinson's Disease Research Center of Excellence, Boston, Massachusetts, USA
    3. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • Penelope Hallett,

    1. Center for Neuroregeneration Research, Harvard Medical School/McLean Hospital, Belmont, Massachusetts, USA
    2. Udall Parkinson's Disease Research Center of Excellence, Boston, Massachusetts, USA
    3. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • Teresia Osborn,

    1. Center for Neuroregeneration Research, Harvard Medical School/McLean Hospital, Belmont, Massachusetts, USA
    2. Udall Parkinson's Disease Research Center of Excellence, Boston, Massachusetts, USA
    3. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • Ole Isacson

    Corresponding author
    1. Center for Neuroregeneration Research, Harvard Medical School/McLean Hospital, Belmont, Massachusetts, USA
    2. Udall Parkinson's Disease Research Center of Excellence, Boston, Massachusetts, USA
    3. Harvard Stem Cell Institute, Boston, Massachusetts, USA
    • Harvard Medical School/McLean Hospital, MRC 1, Belmont, Massachusetts 02478, USA
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    • Telephone: +1-617-855-3283; Fax: +1-617-855-2522


  • Author contributions: M.D.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; G.H., P.H., and T.O.: collection and/or assembly of data, final approval of manuscript; O.I.: conception and design, grant support, data analysis and interpretation, manuscript writing, final approval of manuscript.

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

  • §

    First published online in STEM CELLSEXPRESS May 23, 2011.

Abstract

Immune rejection and risk of tumor formation are perhaps the greatest hurdles in the field of stem cell transplantation. Here, we report the generation of several lines of induced pluripotent stem cells (iPSCs) from cynomolgus macaque (CM) skin fibroblasts carrying specific major histocompatibility complex (MHC) haplotypes. To develop a collection of MHC-matched iPSCs, we genotyped the MHC locus of 25 CMs by microsatellite polymerase chain reaction analysis. Using retroviral infection of dermal skin fibroblasts, we generated several CM-iPSC lines carrying different haplotypes. We characterized the immunological properties of CM-iPSCs and demonstrated that CM-iPSCs can be induced to differentiate in vitro along specific neuronal populations, such as midbrain dopaminergic (DA) neurons. Midbrain-like DA neurons generated from CM-iPSCs integrated into the striatum of a rodent model of Parkinson's disease and promoted behavioral recovery. Importantly, neither tumor formation nor inflammatory reactions were observed in the transplanted animals up to 6 months after transplantation. We believe that the generation and characterization of such histocompatible iPSCs will allow the preclinical validation of safety and efficacy of iPSCs for neurodegenerative diseases and several other human conditions in the field of regenerative medicine. STEM CELLS 2011;29:1052–1063

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