Direct induction of ramified microglia-like cells from human monocytes: Dynamic microglial dysfunction in Nasu-Hakola disease

Masahiro Ohgidani, Takahiro A. Kato, Daiki Setoyama, Noriaki Sagata, Ryota Hashimoto, Kazue Shigenobu, Tetsuhiko Yoshida, Kohei Hayakawa, Norihiro Shimokawa, Daisuke Miura, Hideo Utsumi, Shigenobu Kanba

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Abstract

Microglia have been implicated in various neurological and psychiatric disorders in rodent and human postmortem studies. However, the dynamic actions of microglia in the living human brain have not been clarified due to a lack of studies dealing with in situ microglia. Herein, we present a novel technique for developing induced microglia-like (iMG) cells from human peripheral blood cells. An optimized cocktail of cytokines, GM-CSF and IL-34, converted human monocytes into iMG cells within 14 days. The iMG cells have microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. To confirm clinical utilities, we developed iMG cells from a patient of Nasu-Hakola disease (NHD), which is suggested to be directly caused by microglial dysfunction, and observed that these cells from NHD express delayed but stronger inflammatory responses compared with those from the healthy control. Altogether, the iMG-technique promises to elucidate unresolved aspects of human microglia in various brain disorders.

Original languageEnglish
Article number4957
JournalScientific reports
Volume4
DOIs
Publication statusPublished - May 14 2014

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Microglia
Monocytes
Cytokines
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
Brain Diseases
Granulocyte-Macrophage Colony-Stimulating Factor
Nervous System Diseases
Psychiatry
Rodentia
Blood Cells
Brain

All Science Journal Classification (ASJC) codes

  • General

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Direct induction of ramified microglia-like cells from human monocytes : Dynamic microglial dysfunction in Nasu-Hakola disease. / Ohgidani, Masahiro; Kato, Takahiro A.; Setoyama, Daiki; Sagata, Noriaki; Hashimoto, Ryota; Shigenobu, Kazue; Yoshida, Tetsuhiko; Hayakawa, Kohei; Shimokawa, Norihiro; Miura, Daisuke; Utsumi, Hideo; Kanba, Shigenobu.

In: Scientific reports, Vol. 4, 4957, 14.05.2014.

Research output: Contribution to journalArticle

Ohgidani, M, Kato, TA, Setoyama, D, Sagata, N, Hashimoto, R, Shigenobu, K, Yoshida, T, Hayakawa, K, Shimokawa, N, Miura, D, Utsumi, H & Kanba, S 2014, 'Direct induction of ramified microglia-like cells from human monocytes: Dynamic microglial dysfunction in Nasu-Hakola disease', Scientific reports, vol. 4, 4957. https://doi.org/10.1038/srep04957
Ohgidani, Masahiro ; Kato, Takahiro A. ; Setoyama, Daiki ; Sagata, Noriaki ; Hashimoto, Ryota ; Shigenobu, Kazue ; Yoshida, Tetsuhiko ; Hayakawa, Kohei ; Shimokawa, Norihiro ; Miura, Daisuke ; Utsumi, Hideo ; Kanba, Shigenobu. / Direct induction of ramified microglia-like cells from human monocytes : Dynamic microglial dysfunction in Nasu-Hakola disease. In: Scientific reports. 2014 ; Vol. 4.
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