Human monocyte-derived microglia-like (iMG) cells: A tool to explore microglial dynamics

Abstract

Recent studies have highlighted the importance of microglia as key immunomodulators in a variety of neuropsychiatric diseases. Postmortem brain analysis and positron emission tomography are representative research approaches to assess microglial activation in human patients and this research has revealed microglial activation in the brains of patients with various neuropsychiatric disorders. However, only limited aspects of microglial activation can be assessed with these methods. To overcome the technical and ethical limitations of collecting human-derived microglia in brain biopsies, we first developed a method to generate directly induced microglia-like (iMG) cells from fresh human peripheral blood monocytes in 2014. These iMG cells can be used to perform dynamic morphological and molecular analyses regarding phagocytic capacity and cytokine release following stress stimulation at the cellular level. Patient-derived iMG cells can potentially serve as an important surrogate marker for estimating microglial activation in the human brain, and may provide previously unknown insights into the dynamic pathophysiology of microglia in patients with neuropsychiatric disorders. Thus, the iMG-based technology could be used as a valuable reverse translational tool and provide new insights into the dynamic molecular pathophysiology of microglia in a wide variety of psychiatric and physical disorders.