Premium
Transnasal transplantation of human induced pluripotent stem cell‐derived microglia to the brain of immunocompetent mice
Author(s) -
Parajuli Bijay,
Saito Hiroki,
Shinozaki Youichi,
Shigetomi Eiji,
Miwa Hiroto,
Yoneda Sosuke,
Tanimura Miki,
Omachi Shigeki,
Asaki Toshiyuki,
Takahashi Koji,
Fujita Masahide,
Nakashima Kinichi,
Koizumi Schuichi
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23985
Subject(s) - microglia , induced pluripotent stem cell , biology , transplantation , stem cell , neuroscience , embryonic stem cell , immune system , human brain , neuroinflammation , microbiology and biotechnology , immunology , medicine , inflammation , biochemistry , gene
Abstract 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.