Exploring iPSCs-derived microglia in psychiatry: methods, implementations, and challenges.

Abstract

Microglia, the principal immune cells of the central nervous system (CNS), have been implicated in playing a key role in psychiatry. These cells are involved in maintaining and protecting the brain against pathogens through mechanisms that promote neuroinflammation. While neuroinflammation is essential for achieving brain homeostasis, its chronic activation can lead to impaired brain function, disrupted neuronal development, and altered synaptic activity. Research into psychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorders (ASD) has shown increased microglia activity and density, although most studies rely on post-mortem tissue or positron emission tomography (PET) imaging. Recent advances in induced pluripotent stem cells (iPSCs)-derived microglia (iMGL) offer new opportunities to study psychiatry disorders at the molecular and cellular levels, potentially leading to a better understanding of these disorders and their underlying mechanisms, as well as contributing to the development of effective biomarkers and treatments. Despite this potential, the application of iMGLs in psychiatric research remains limited. This review discusses the formation and function of microglia in both health and psychiatric conditions. Additionally, outlines various protocols for generating iMGLs, evaluates their current research applications, and addresses the limitations and associated challenges.