Journal Article MHC matching improves engraftment of iPSC-derived neurons in non-human primates

Morizane, Asuka  ,  Kikuchi, Tetsuhiro  ,  Hayashi, Takuya  ,  Mizuma, Hiroshi  ,  Takara, Sayuki  ,  Doi, Hisashi  ,  Mawatari, Aya  ,  Glasser, Matthew F.  ,  Shiina, Takashi  ,  Ishigaki, Hirohito  ,  Itoh, Yasushi  ,  Okita, Keisuke  ,  Yamasaki, Emi  ,  Doi, Daisuke  ,  Onoe, Hirotaka  ,  Ogasawara, Kazumasa  ,  Yamanaka, Shinya  ,  Takahashi, Jun

82017-08-30 , Springer Nature
iPS細胞由来神経細胞の他家移植におけるMHC適合の有用性. 京都大学プレスリリース. 2017-09-04.
The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.

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