Exploring microglial replacement: From disease models to clinical translation

Abstract

Microglia, the resident immune cells of the central nervous system (CNS), play pivotal roles in immune surveillance, synaptic remodeling, and neuroinflammatory responses. Recent interest has focused on microglial replacement therapy to renew microglial populations, mitigate neuroinflammation, and deliver functional genes. This review synthesizes current research on the potential applications of microglial replacement therapy, highlighting preclinical studies employing diverse depletion models, the source of replaced microglia, and their impacts on CNS disorders. Moreover, challenges and considerations for the clinical translation of microglial replacement therapy are discussed. Overall, microglial replacement therapy holds promise for restoring CNS homeostasis and ameliorating neuroinflammation, offering new avenues for the development of disease-modifying treatments for CNS disorders.