Possible NK cell-mediated immune responses against iPSC-derived cells in allogeneic transplantation settings

In the regenerative medicine field, allogenic transplantation of regenerated tissues has been promoted because autologous transplantation setting is costly and time-consuming to prepare and therefore unsuitable for emergent treatment. To avoid a T cell-mediated immune rejection in the allogenic transplantation setting, induced pluripotent stem cells (iPSCs) derived from different HLA haplotype-homozygous (HLA-homo) donors have been prepared to be used as source of regenerated tissues. However, there still remain immunological issues, even when HLA-homo iPSCs are used. One issue is the immune response against minor histocompatibility antigens expressed on the regenerated tissues, and the other is the immune rejection mediated by NK cells. In this article, we introduce our research on NK cell reactivity against the regenerated tissues in the HLA homo-to-hetero transplantation setting. We further introduce several approaches taken by other groups that address the NK-mediated immune rejection issue.