Transnasal transplantation of human induced pluripotent stem cell-derived microglia to the brain of immunocompetent mice

Bijay Parajuli, Hiroki Saito, Youichi Shinozaki, Eiji Shigetomi, Hiroto Miwa, Sosuke Yoneda, Miki Tanimura, Shigeki Omachi, Toshiyuki Asaki, Koji Takahashi, Masahide Fujita, Kinichi Nakashima, Schuichi Koizumi

研究成果: Contribution to journalArticle査読

1 被引用数 (Scopus)

抄録

Microglia are the resident immune cells of the brain, and play essential roles in neuronal development, homeostatic function, and neurodegenerative disease. Human microglia are relatively different from mouse microglia. However, most research on human microglia is performed in vitro, which does not accurately represent microglia characteristics under in vivo conditions. To elucidate the in vivo characteristics of human microglia, methods have been developed to generate and transplant induced pluripotent or embryonic stem cell-derived human microglia into neonatal or adult mouse brains. However, its widespread use remains limited by the technical difficulties of generating human microglia, as well as the need to use immune-deficient mice and conduct invasive surgeries. To address these issues, we developed a simplified method to generate induced pluripotent stem cell-derived human microglia and transplant them into the brain via a transnasal route in immunocompetent mice, in combination with a colony stimulating factor 1 receptor antagonist. We found that human microglia were able to migrate through the cribriform plate to different regions of the brain, proliferate, and become the dominant microglia in a region-specific manner by occupying the vacant niche when exogenous human cytokine is administered, for at least 60 days.

本文言語英語
ページ(範囲)2332-2348
ページ数17
ジャーナルGLIA
69
10
DOI
出版ステータス出版済み - 10 2021

All Science Journal Classification (ASJC) codes

  • 神経学
  • 細胞および分子神経科学

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