Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro

Masahiro Ozaki, Akio Iwanami, Narihito Nagoshi, Jun Kohyama, Go Itakura, Hiroki Iwai, Soraya Nishimura, Yuichiro Nishiyama, Soya Kawabata, Keiko Sugai, Tsuyoshi Iida, Kohei Matsubayashi, Miho Isoda, Rei Kashiwagi, Yoshiaki Toyama, Morio Matsumoto, Hideyuki Okano, Masaya Nakamura

研究成果: Article査読

18 被引用数 (Scopus)

抄録

To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries. In this study, we evaluated the significance of HLA matching in hiPSC-NS/PC transplantation by performing modified mixed lymphocyte reaction (MLR) assays with hiPSC-NS/PCs. Compared to fetus-derived NS/PCs, the expression levels of human leukocyte antigen-antigen D related (HLA-DR) and co-stimulatory molecules on hiPSC-NS/PCs were significantly low, even with the addition of tumor necrosis factor-α (TNFα) and/or interferon-γ (IFNγ) to mimic the inflammatory environment surrounding transplanted hiPSC-NS/PCs in injured tissues. Interestingly, both the allogeneic HLA-matched and the HLA-mismatched responses were similarly low in the modified MLR assay. Furthermore, the autologous response was also similar to the allogeneic response. hiPSC-NS/PCs suppressed the proliferative responses of allogeneic HLA-mismatched peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. Thus, the low antigen-presenting function and immunosuppressive effects of hiPSC-NS/PCs result in a depressed immune response, even in an allogeneic HLA-mismatched setting. It is crucial to verify whether these in vitro results are reproducible in a clinical setting.

本文言語English
ページ(範囲)128-138
ページ数11
ジャーナルStem Cell Research
19
DOI
出版ステータスPublished - 2017 3月 1

ASJC Scopus subject areas

  • 発生生物学
  • 細胞生物学

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