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Human Embryonic Stem Cells Possess Immune-Privileged Properties

^a Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine and FOCIS Centre for Clinical Immunology and Immunotherapeutics, London, Ontario, Canada;
^b Geron Corporation, Menlo Park, California;
^c The University of Western Ontario, Department of Microbiology and Immunology and Medicine, London, Ontario, Canada.

Key Words. Human embryonic stem cells • Immune response • Transplantation • Tolerance • T-cell proliferation

Correspondence: Mickie Bhatia, M.D., 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; e-mail: mbhatia{at}robarts.ca

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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