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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)128-138
Number of pages11
JournalStem Cell Research
Volume19
DOIs
Publication statusPublished - 2017 Mar 1

Keywords

  • HLA
  • Immunomodulatory function
  • iPS cell-derived neural stem/progenitor cells
  • Mixed lymphocyte reaction

ASJC Scopus subject areas

  • Medicine(all)
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Ozaki, M., Iwanami, A., Nagoshi, N., Kohyama, J., Itakura, G., Iwai, H., Nishimura, S., Nishiyama, Y., Kawabata, S., Sugai, K., Iida, T., Matsubayashi, K., Isoda, M., Kashiwagi, R., Toyama, Y., Matsumoto, M., Okano, H., & Nakamura, M. (2017). Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro. Stem Cell Research, 19, 128-138. https://doi.org/10.1016/j.scr.2017.01.007