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Nat Biotechnol. 2019 Mar;37(3):252-258. doi: 10.1038/s41587-019-0016-3. Epub 2019 Feb 18.

Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients.

Author information

1
Department of Surgery, Division of Cardiothoracic Surgery, Transplant and Stem Cell Immunobiology-Lab, University of California San Francisco, San Francisco, CA, USA.
2
Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.
3
Cardiovascular Research Center Hamburg and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.
4
Division of Infectious Diseases, UNC Center for AIDS Research, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
5
Howard Hughes Medical Institute, Institute for Immunity, Transplantation and Infection, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
6
Department of Microbiology and Immunology and the Parker Institute for Cancer Immunotherapy, University of California San Francisco, San Francisco, California, USA.
7
Department of Surgery, Division of Cardiothoracic Surgery, Transplant and Stem Cell Immunobiology-Lab, University of California San Francisco, San Francisco, CA, USA. Sonja.Schrepfer@ucsf.edu.

Abstract

Autologous induced pluripotent stem cells (iPSCs) constitute an unlimited cell source for patient-specific cell-based organ repair strategies. However, their generation and subsequent differentiation into specific cells or tissues entail cell line-specific manufacturing challenges and form a lengthy process that precludes acute treatment modalities. These shortcomings could be overcome by using prefabricated allogeneic cell or tissue products, but the vigorous immune response against histo-incompatible cells has prevented the successful implementation of this approach. Here we show that both mouse and human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed. These hypoimmunogenic iPSCs retain their pluripotent stem cell potential and differentiation capacity. Endothelial cells, smooth muscle cells, and cardiomyocytes derived from hypoimmunogenic mouse or human iPSCs reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression. These findings suggest that hypoimmunogenic cell grafts can be engineered for universal transplantation.

PMID:
30778232
DOI:
10.1038/s41587-019-0016-3

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