Journal
CELLS
Volume 10, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/cells10020476
Keywords
allograft rejection; human iPS cell; liver bud; humanized mouse
Categories
Funding
- Japan Agency for Medical Research and Development (AMED)
- Center for Clinical Application Research on Specific Disease/Organ from the Research Center Network for the Realization of Regenerative Medicine
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By introducing human leukocyte antigen into immune-compromised mice, researchers were able to replicate human immune responses in a new model, providing insights for transplantation research.
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-2R gamma KO 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.
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