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Kidney Int., Mar 22 2025, S0085-2538(25)00255-8 | https://doi.org/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 1,2∗, John Yongjoon Choi 2∗, Jamie Kady 3, Marina De Cos 1, Jenny S. Wong 1, Emily King 1, Nour Younis 2, Nadim Al Rahy 2,7, Soltan Al Chaar 2,7, Houda Djebli 2,8, Siawosh Eskandari 2, Stephen Samuel 2, Tamara Merhej 2, Nivedha Sukumar 2,9, Jia-Ren Lin 5, Jia-Yun Chen 5, Yilin Xu 5, Sandro Santagata 5,6, Astrid Weins 6, Melissa Yeung 2, Paolo Cravedi 1, Kirk N. Campbell 1, Dario Lemos 2,4, Joseph V. Bonventre 2,4,10#, Michael Brehm 3#, Jamil Azzi 2#
1Nephrology Division, Department of Medicine, Mount Sinai Hospital, New York, New York
2Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
3University of Massachusetts, Worcester, Massachusetts
4Harvard Stem Cell Institute
5Department of Systems Biology, Harvard Medical School, Boston, Massachusetts
6Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
7Doctoral School of Science and Technology, Lebanese University, Beirut, Lebanon
8Institute of Biological Science, Faculty of Medical Sciences, Mohammed VI Polytechnic University, Benguerir, Morocco
9Northeastern University, Boston, Massachusetts
10Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
∗Co-first author
#Co-corresponding author
Corresponding author: Jamil Azzi
1Nephrology Division, Department of Medicine, Mount Sinai Hospital, New York, New York
2Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
3University of Massachusetts, Worcester, Massachusetts
4Harvard Stem Cell Institute
5Department of Systems Biology, Harvard Medical School, Boston, Massachusetts
6Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
7Doctoral School of Science and Technology, Lebanese University, Beirut, Lebanon
8Institute of Biological Science, Faculty of Medical Sciences, Mohammed VI Polytechnic University, Benguerir, Morocco
9Northeastern University, Boston, Massachusetts
10Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
∗Co-first author
#Co-corresponding author
Corresponding author: Jamil Azzi
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.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-26)
- 국외 연구진
- 생명과학 > 면역학
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