Development of In vitro Models of Microglia Mediated Myelin Phagocytosis

Multiple Sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS), characterized by demyelination of neurons and subsequent axonal loss, leading to impaired neuronal function and communication. The CNS inflammatory arm which contributes to the demyelination and gradual neuroaxonal loss in progressive patients resides primarily behind an uncompromised BBB with lesions being predominantly chronic active and smoldering in nature. Microglia, the CNS-resident immune cells, are the “macrophages” of the brain and have emerged as a critical cellular subset implicated in the etiology of MS. Here, we evaluate in vitro models of studying microglia functions for context-dependent interrogation of how this well-versed and highly dynamic CNS-resident immune cell responds to myelin debris, a substrate relevant in MS pathology. Such learnings could lead to understanding the benefits and limitations of microglia in vitro models as platforms for elucidating on novel microglia physiological functions, pathways, and/or molecules which are involved in uptake and clearance of myelin debris, with the ultimate goal of understanding how to best utilize microglial biology and functions to promote an environment for remyelination and neurorepair in MS patients.