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Article

Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models

1
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
2
Division of Regenerative Medicine, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
3
Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Sapporo, Hokkaido 060-0815, Japan
4
Central Institute for Experimental Animals (CIEA), Kawasaki 210-0821, Japan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Hiroshi Yagi
Cells 2021, 10(2), 476; https://doi.org/10.3390/cells10020476
Received: 9 January 2021 / Revised: 5 February 2021 / Accepted: 18 February 2021 / Published: 23 February 2021
(This article belongs to the Special Issue Current Progress in Organ Regeneration: Cells, Organoids and Organs)
Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice. After the transplantation of HLA-A2 human hematopoietic stem cells into NOG-HLA-A2Tg, we succeeded in achieving alloimmune responses after the HLA-mismatched human-induced pluripotent stem cell (hiPSC)-derived liver-like tissue transplantation. This immune response was inhibited by administering tacrolimus. In this model, we reproduced allograft rejection after the human iPSC-derived liver-like tissue transplantation. Human tissue transplantation on the humanized mouse liver surface is a good model that can predict T-cell-mediated cellular rejection that may occur when organ transplantation is performed. View Full-Text
Keywords: allograft rejection; human iPS cell; liver bud; humanized mouse allograft rejection; human iPS cell; liver bud; humanized mouse
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MDPI and ACS Style

Mori, A.; Murata, S.; Tashiro, N.; Tadokoro, T.; Okamoto, S.; Otsuka, R.; Wada, H.; Murata, T.; Takahashi, T.; Seino, K.-i.; Taniguchi, H. Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models. Cells 2021, 10, 476. https://doi.org/10.3390/cells10020476

AMA Style

Mori A, Murata S, Tashiro N, Tadokoro T, Okamoto S, Otsuka R, Wada H, Murata T, Takahashi T, Seino K-i, Taniguchi H. Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models. Cells. 2021; 10(2):476. https://doi.org/10.3390/cells10020476

Chicago/Turabian Style

Mori, Akihiro, Soichiro Murata, Nao Tashiro, Tomomi Tadokoro, Satoshi Okamoto, Ryo Otsuka, Haruka Wada, Tomoki Murata, Takeshi Takahashi, Ken-ichiro Seino, and Hideki Taniguchi. 2021. "Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models" Cells 10, no. 2: 476. https://doi.org/10.3390/cells10020476

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