Cited by 758Pluripotent Stem Cells ResearchOrgan and Tissue Transplantation ResearchMesenchymal stem cell research

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

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Deuse, Tobias, Hu, Xiaomeng, Gravina, Alessia, Wang, Dong, Tediashvili, Grigol, De, Chandrav, Thayer, William O., Wahl, Angela, Garcia, J. Victor, Reichenspurner, Hermann, Davis, Mark M., Lanier, Lewis L., Schrepfer, Sonja·2019·Nature Biotechnology

DOI 10.1038/s41587-019-0016-3PMC PMC6419516

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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.

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Authors: Deuse, T., Hu, X., Gravina, A., Wang, D., Tediashvili, G., De, C., Thayer, W. O., Wahl, A., Garcia, J. V., Reichenspurner, H., Davis, M. M., Lanier, L. L., & Schrepfer, S.
Affiliations: University of California, San Francisco (US)
Universität Hamburg (DE)
University of North Carolina at Chapel Hill (US)
Howard Hughes Medical Institute (US)
Corresponding author: Schrepfer, Sonja
ORCID: Deuse, Tobias
Hu, Xiaomeng
Gravina, Alessia
Wang, Dong
Tediashvili, Grigol
De, Chandrav
Wahl, Angela
Davis, Mark M.
Lanier, Lewis L.
Schrepfer, Sonja
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2019-02-18
Volume: 37
Issue: 3
Pages: 252-258
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/s41587-019-0016-3
PMC: PMC6419516
OpenAlex: W2911604931
Cited by: 758
References: 31
Citations by year: 2026: 98 · 2025: 102 · 2024: 102 · 2023: 113 · 2022: 94 · 2021: 97 · 2020: 106 · 2019: 46
FWCI: 28.36
Type: journal article
Language: en
Update notices: correction (2022-09-16)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Biotechnology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL140236)
National Institute of Mental Health (R01MH108179)
National Institute of Allergy and Infectious Diseases (R01AI068129, R01AI111899, R01AI123010, U19AI057229)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Health Sciences › Medicine › Transplantation › Organ and Tissue Transplantation Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords: induced pluripotent stem cells, immune rejection, allogeneic transplantation, MHC mismatch, endothelial cells, smooth muscle cells, cardiomyocytes, immunosuppression-free transplantation
MeSH terms: Animals, Cell Differentiation, Graft Rejection, HLA Antigens, Humans, Transplantation, Homologous, Histocompatibility Antigens Class I, Myocytes, Cardiac, Mice, Induced Pluripotent Stem Cells

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

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