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.

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