Human Embryonic Stem Cells Possess Immune-Privileged Properties

Authors

  • Li Li,

    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
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  • Miren L. Baroja,

    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
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  • Anish Majumdar,

    1. Geron Corporation, Menlo Park, California
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  • Kristin Chadwick,

    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
    2. The University of Western Ontario, Department of Microbiology and Immunology and Medicine, London, Ontario, Canada
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  • Anne Rouleau,

    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
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  • Lisa Gallacher,

    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
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  • Iris Ferber,

    1. Geron Corporation, Menlo Park, California
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  • Jane Lebkowski,

    1. Geron Corporation, Menlo Park, California
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  • Tanya Martin,

    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
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  • Joaquin Madrenas,

    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
    2. The University of Western Ontario, Department of Microbiology and Immunology and Medicine, London, Ontario, Canada
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  • Mickie Bhatia M.D.

    Corresponding author
    1. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada
    2. The University of Western Ontario, Department of Microbiology and Immunology and Medicine, London, Ontario, Canada
    • Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine, 100 Perth Drive, London, Ontario, Canada, N6A5K8. Telephone: 519-663-5777 ext. 34166; Fax: 519-663-2982
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Abstract

Human embryonic stem cells (hESCs) are envisioned to be a major source for cell-based therapies. Efforts to overcome rejection of hESCs include nuclear transfer and collection of hESC banks representing the broadest diversity of major histocompatability complex (MHC) polymorphorisms. Surprisingly, immune responses to hESCs have yet to be experimentally evaluated. Here, injection of hESCs into immune-competent mice was unable to induce an immune response. Undifferentiated and differentiated hESCs failed to stimulate proliferation of alloreactive primary human T cells and inhibited third-party allogeneic dendritic cell-mediated T-cell proliferation via cellular mechanisms independent of secreted factors. Upon secondary rechallenge, T cells cocultured with hESCs were still responsive to allogeneic stimulators but failed to proliferate upon re-exposure to hESCs. Our study demonstrates that hESCs possess unique immune-privileged characteristics and provides an unprecedented opportunity to further investigate the mechanisms of immune response to transplantation of hESCs that may avoid immune-mediated rejection.

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