Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

Samuel Mon-Wei Yu¹, John Yongjoon Choi², Jamie Kady³, Marina De Cos⁴, Jenny S Wong⁴, Emily King⁴, Nour Younis², Nadim Al Rahy⁵, Soltan Al Chaar⁵, Houda Djebli⁶, Siawosh Eskandari², Stephen Samuel², Tamara Merhej², Nivedha Sukumar⁷, Jia-Ren Lin⁸, Jia-Yun Chen⁸, Yilin Xu⁸, Sandro Santagata⁹, Astrid Weins¹⁰, Melissa Yeung², Paolo Cravedi⁴, Kirk N Campbell⁴, Dario Lemos¹¹, Joseph V Bonventre¹², Michael A Brehm¹³, Jamil Azzi¹⁴

Affiliations

¹ Department of Medicine, Nephrology Division, Mount Sinai Hospital, New York, New York, USA; Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
⁴ Department of Medicine, Nephrology Division, Mount Sinai Hospital, New York, New York, USA.
⁵ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Doctoral School of Science and Technology, Lebanese University, Beirut, Lebanon.
⁶ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Institute of Biological Science, Faculty of Medical Sciences, Mohammed VI Polytechnic University, Benguerir, Morocco.
⁷ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Biotechnology, Northeastern University, Boston, Massachusetts, USA.
⁸ Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
¹² Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA; Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: joseph_bonventre@hms.harvard.edu.
¹³ Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA. Electronic address: michael.brehm@umassmed.edu.
¹⁴ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: jazzi@bwh.harvard.edu.

PMID: 40127865
PMCID: PMC12145861 (available on 2026-06-01)
DOI: 10.1016/j.kint.2025.02.027

Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

Samuel Mon-Wei Yu et al. Kidney Int. 2025 Jun.

. 2025 Jun;107(6):1011-1016.

doi: 10.1016/j.kint.2025.02.027. Epub 2025 Mar 22.

Authors

Affiliations

¹ Department of Medicine, Nephrology Division, Mount Sinai Hospital, New York, New York, USA; Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
⁴ Department of Medicine, Nephrology Division, Mount Sinai Hospital, New York, New York, USA.
⁵ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Doctoral School of Science and Technology, Lebanese University, Beirut, Lebanon.
⁶ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Institute of Biological Science, Faculty of Medical Sciences, Mohammed VI Polytechnic University, Benguerir, Morocco.
⁷ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Biotechnology, Northeastern University, Boston, Massachusetts, USA.
⁸ Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
¹² Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA; Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: joseph_bonventre@hms.harvard.edu.
¹³ Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA. Electronic address: michael.brehm@umassmed.edu.
¹⁴ Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: jazzi@bwh.harvard.edu.

PMID: 40127865
PMCID: PMC12145861 (available on 2026-06-01)
DOI: 10.1016/j.kint.2025.02.027

Abstract

Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids ex vivo. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity.

Keywords: human kidney organoids; humanized mice model; kidney transplantation.

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Conflict of interest statement

DISCLOSURES

JVB is an inventor on kidney organoid patents assigned to MassGeneralBrigham.

References

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Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

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Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

Authors

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Conflict of interest statement

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