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

doi:10.1038/srep04957

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

Sci Rep. 2014 May 14:4:4957. doi: 10.1038/srep04957.

Affiliations

¹ Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University.
² 1] Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University [2] Innovation Center for Medical Redox Navigation, Kyushu University.
³ Innovation Center for Medical Redox Navigation, Kyushu University.
⁴ 1] Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University [2] Department of Psychiatry, Osaka University Graduate School of Medicine.
⁵ Department of Psychiatry, Asakayama General Hospital.
⁶ Department of Psychiatry, Osaka University Graduate School of Medicine.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Cell Differentiation* / drug effects
Cytokines / metabolism
Cytokines / pharmacology
Female
Humans
Immunophenotyping
Inflammation Mediators / metabolism
Lipodystrophy / genetics
Lipodystrophy / immunology
Lipodystrophy / metabolism
Lipodystrophy / pathology
Membrane Proteins / genetics
Membrane Proteins / metabolism
Microglia / cytology*
Microglia / drug effects
Microglia / metabolism*
Middle Aged
Monocytes / cytology*
Monocytes / drug effects
Monocytes / metabolism*
Osteochondrodysplasias / genetics
Osteochondrodysplasias / immunology
Osteochondrodysplasias / metabolism
Osteochondrodysplasias / pathology
RNA Interference
Subacute Sclerosing Panencephalitis / genetics
Subacute Sclerosing Panencephalitis / immunology
Subacute Sclerosing Panencephalitis / metabolism
Subacute Sclerosing Panencephalitis / pathology

Substances

Adaptor Proteins, Signal Transducing
Cytokines
Inflammation Mediators
Membrane Proteins
TYROBP protein, human

Supplementary concepts

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy