IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms4903.html
   My bibliography  Save this article

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

Author

Listed:
  • Patricia .E de Almeida

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Everett H. Meyer

    (Stanford University School of Medicine)

  • Nigel G. Kooreman

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Sebastian Diecke

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Devaveena Dey

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Veronica Sanchez-Freire

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Shijun Hu

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Antje Ebert

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Justin Odegaard

    (Stanford University School of Medicine)

  • Nicholas M. Mordwinkin

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Thomas P. Brouwer

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • David Lo

    (Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
    Stanford University School of Medicine)

  • Daniel T. Montoro

    (Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
    Stanford University School of Medicine)

  • Michael T. Longaker

    (Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
    Stanford University School of Medicine)

  • Robert S. Negrin

    (Stanford University School of Medicine)

  • Joseph C. Wu

    (Stanford University School of Medicine
    Stanford Cardiovascular Institute, Stanford University School of Medicine
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

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.

Suggested Citation

  • Patricia .E de Almeida & Everett H. Meyer & Nigel G. Kooreman & Sebastian Diecke & Devaveena Dey & Veronica Sanchez-Freire & Shijun Hu & Antje Ebert & Justin Odegaard & Nicholas M. Mordwinkin & Thomas, 2014. "Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4903
    DOI: 10.1038/ncomms4903
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms4903
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms4903?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4903. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.