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

Author

Listed:
  • 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)
    Kyoto University Graduate School of Medicine)

  • Kazumasa Ogasawara

    (Shiga University of Medical Science)

  • Shinya Yamanaka

    (Center for iPS Cell Research and Application, Kyoto University
    San Francisco)

  • Jun Takahashi

    (Center for iPS Cell Research and Application, Kyoto University
    Kyoto University Graduate School of Medicine)

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.

Suggested Citation

  • Asuka Morizane & Tetsuhiro Kikuchi & Takuya Hayashi & Hiroshi Mizuma & Sayuki Takara & Hisashi Doi & Aya Mawatari & Matthew F. Glasser & Takashi Shiina & Hirohito Ishigaki & Yasushi Itoh & Keisuke Oki, 2017. "MHC matching improves engraftment of iPSC-derived neurons in non-human primates," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00926-5
    DOI: 10.1038/s41467-017-00926-5
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    Cited by:

    1. Kengo Abe & Akihiro Yamashita & Miho Morioka & Nanao Horike & Yoshiaki Takei & Saeko Koyamatsu & Keisuke Okita & Shuichi Matsuda & Noriyuki Tsumaki, 2023. "Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yun Chang & Xuechao Cai & Ramizah Syahirah & Yuxing Yao & Yang Xu & Gyuhyung Jin & Vijesh J. Bhute & Sandra Torregrosa-Allen & Bennett D. Elzey & You-Yeon Won & Qing Deng & Xiaojun Lance Lian & Xiaogu, 2023. "CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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