TY - JOUR
T1 - Transnasal transplantation of human induced pluripotent stem cell-derived microglia to the brain of immunocompetent mice
AU - Parajuli, Bijay
AU - Saito, Hiroki
AU - Shinozaki, Youichi
AU - Shigetomi, Eiji
AU - Miwa, Hiroto
AU - Yoneda, Sosuke
AU - Tanimura, Miki
AU - Omachi, Shigeki
AU - Asaki, Toshiyuki
AU - Takahashi, Koji
AU - Fujita, Masahide
AU - Nakashima, Kinichi
AU - Koizumi, Schuichi
N1 - Funding Information:
Grant sponsors: This study was supported by JSPS KAKENHI 17 K14961 (PB), 20 K15899 (PB), 20H05902 (SK), 20H05060 (SK), 19H04746 (SK), AMED 21bm0404057 (KN), AMED‐CREST 25gm1310008 (SK, KN), CREST (SK), the Mitsubishi Science Foundation (SK), the Takeda Science Foundation (SK), and a Frontier Brain Science Grant from the University of Yamanashi (SK). We thank Koizumi‐Lab members, and Junji Tsuchida, Yukiko Yamatsu and Yusaku Masago from Shionogi & Co. Ltd for technical supports and helpful advice. We also thank Bronwen Gardner, PhD, from Edanz Group ( https://en-author-services.edanz.com/ ) for editing a draft of this manuscript.
Funding Information:
AMED‐CREST, Grant/Award Number: 25gm1310008; Core Research for Evolutional Science and Technology, Grant/Award Number: JPMJCR14G2; Frontier Brain Science Grant from the University of Yamanashi; Japan Agency for Medical Research and Development, Grant/Award Number: 21bm0404057; Japan Society for the Promotion of Science, Grant/Award Numbers: KAKENHI (17K14961), KAKENHI (19H04746), KAKENHI (20H05060), KAKENHI (20H05902), KAKENHI (20K15899); Mitsubishi Foundation; Takeda Medical Research Foundation Funding information
Funding Information:
Grant sponsors: This study was supported by JSPS KAKENHI 17 K14961 (PB), 20 K15899 (PB), 20H05902 (SK), 20H05060 (SK), 19H04746 (SK), AMED 21bm0404057 (KN), AMED-CREST 25gm1310008 (SK, KN), CREST (SK), the Mitsubishi Science Foundation (SK), the Takeda Science Foundation (SK), and a Frontier Brain Science Grant from the University of Yamanashi (SK). We thank Koizumi-Lab members, and Junji Tsuchida, Yukiko Yamatsu and Yusaku Masago from Shionogi & Co. Ltd for technical supports and helpful advice. We also thank Bronwen Gardner, PhD, from Edanz Group (https://en-author-services.edanz.com/) for editing a draft of this manuscript.
Publisher Copyright:
© 2021 The Authors. Glia published by Wiley Periodicals LLC.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
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U2 - 10.1002/glia.23985
DO - 10.1002/glia.23985
M3 - Article
C2 - 34309082
AN - SCOPUS:85111435425
VL - 69
SP - 2332
EP - 2348
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 10
ER -