Lessons from ex vivo and in vitro models in microglia research

Microglia are resident immune cells of the central nervous system (CNS) that dynamically adapt to their microenvironment to achieve multiple housekeeping roles. While ex vivo and in vitro models are instrumental tools to study microglial function, the slicing or culturing process inherently leads to markedly altered microglial phenotypes. Understanding the nature of these limitations and developing better ex vivo and in vitro models are crucial for enhancing the utility of these methods. In this review, we discuss recent developments in ex vivo and in vitro microglia models, from cell cultures to brain slices, focusing on the mechanisms that may need to be considered when using these tools and interpreting the obtained results. We suggest that limitations of ex vivo and in vitro models also provide opportunities to better understand the mechanisms driving microglial phenotype changes in various disease states.