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

Asuka Morizane, Tetsuhiro Kikuchi, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Hisashi Doi, Aya Mawatari, Matthew F. Glasser, Takashi Shiina, Hirohito Ishigaki, Yasushi Itoh, Keisuke Okita, Emi Yamasaki, Daisuke Doi, Hirotaka Onoe, Kazumasa Ogasawara, Shinya Yamanaka and Jun Takahashi ()
Additional contact information
Asuka Morizane: Center for iPS Cell Research and Application, Kyoto University
Tetsuhiro Kikuchi: Center for iPS Cell Research and Application, Kyoto University
Takuya Hayashi: RIKEN Center for Life Science Technologies (CLST)
Hiroshi Mizuma: RIKEN Center for Life Science Technologies (CLST)
Sayuki Takara: RIKEN Center for Life Science Technologies (CLST)
Hisashi Doi: RIKEN Center for Life Science Technologies (CLST)
Aya Mawatari: RIKEN Center for Life Science Technologies (CLST)
Matthew F. Glasser: Washington University School of Medicine
Takashi Shiina: Tokai University, School of Medicine
Hirohito Ishigaki: Shiga University of Medical Science
Yasushi Itoh: Shiga University of Medical Science
Keisuke Okita: Center for iPS Cell Research and Application, Kyoto University
Emi Yamasaki: Center for iPS Cell Research and Application, Kyoto University
Daisuke Doi: Center for iPS Cell Research and Application, Kyoto University
Hirotaka Onoe: RIKEN Center for Life Science Technologies (CLST)
Kazumasa Ogasawara: Shiga University of Medical Science
Shinya Yamanaka: Center for iPS Cell Research and Application, Kyoto University
Jun Takahashi: Center for iPS Cell Research and Application, Kyoto University

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00926-5

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