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

被引：115

作者：

de Almeida, Patricia E. ^{[1
,2
,3
,4
]}

Meyer, Everett H. ^{[5
]}

Kooreman, Nigel G. ^{[1
,2
,3
,4
]}

Diecke, Sebastian ^{[1
,2
,3
,4
]}

Dey, Devaveena ^{[1
,2
,3
,4
]}

Sanchez-Freire, Veronica ^{[1
,2
,3
,4
]}

Hu, Shijun ^{[1
,2
,3
,4
]}

Ebert, Antje ^{[1
,2
,3
,4
]}

Odegaard, Justin ^{[6
]}

Mordwinkin, Nicholas M. ^{[1
,2
,3
,4
]}

Brouwer, Thomas P. ^{[1
,2
,3
,4
]}

Lo, David ^{[4
,7
]}

Montoro, Daniel T. ^{[4
,7
]}

Longaker, Michael T. ^{[4
,7
]}

Negrin, Robert S. ^{[5
]}

Wu, Joseph C. ^{[1
,2
,3
,4
]}

机构：

[1] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Dept Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[7] Stanford Univ, Sch Med, Dept Surg, Div Plast & Reconstruct Surg, Stanford, CA 94305 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

REGULATORY T-CELLS; EPIGENETIC MEMORY; HUMAN FIBROBLASTS; REJECTION; REPERTOIRE; INDUCTION; RESPONSES; DISEASE; INNATE; CANCER;

D O I：

10.1038/ncomms4903

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-gamma, 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.

引用

页数：12

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