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Nat Commun. 2014 May 30;5:3903. doi: 10.1038/ncomms4903.

Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance.

Author information

1
1] Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, California 94305-5323, USA [2] Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305-5323, USA [3] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305-5323, USA [4].
2
1] Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, California 94305-5323, USA [2].
3
1] Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, California 94305-5323, USA [2] Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305-5323, USA [3] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305-5323, USA.
4
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5323, USA.
5
1] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305-5323, USA [2] Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, California 94305-5323, USA.
6
Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, California 94305-5323, USA.

Abstract

The exact nature of the immune response elicited by autologous-induced pluripotent stem cell (iPSC) progeny is still not well understood. Here we show in murine models that autologous iPSC-derived endothelial cells (iECs) elicit an immune response that resembles the one against a comparable somatic cell, the aortic endothelial cell (AEC). These cells exhibit long-term survival in vivo and prompt a tolerogenic immune response characterized by elevated IL-10 expression. In contrast, undifferentiated iPSCs elicit a very different immune response with high lymphocytic infiltration and elevated IFN-γ, granzyme-B and perforin intragraft. Furthermore, the clonal structure of infiltrating T cells from iEC grafts is statistically indistinguishable from that of AECs, but is different from that of undifferentiated iPSC grafts. Taken together, our results indicate that the differentiation of iPSCs results in a loss of immunogenicity and leads to the induction of tolerance, despite expected antigen expression differences between iPSC-derived versus original somatic cells.

PMID:
24875164
PMCID:
PMC4075468
DOI:
10.1038/ncomms4903
[Indexed for MEDLINE]
Free PMC Article
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