Modeling Cellular Crosstalk of Neuroinflammation Axis by Tri-cultures of iPSC-Derived Human Microglia, Astrocytes, and Neurons

Neuroinflammation is a common early pathological feature in many neurodegenerative disorders, including Alzheimer's disease (AD), which has been heavily implicated as a causative factor in disease pathology. However, the role neuroinflammation and inflammatory cells, including microglia and astrocytes, play in AD development and progression has not been fully defined. To try to better understand and study this neuroinflammatory role in AD pathogenesis, researchers use a variety of model systems, particularly in vivo animal models. Despite their usefulness, these models do come with a variety of limitations due to the inherent complexity of the brain and the human-specific nature of AD. Here, we describe a reductionist approach at modeling neuroinflammation by utilizing an in vitro tri-culture system of neurons, astrocytes, and microglia induced from human pluripotent stem cells. This tri-culture model is a powerful tool to dissect intercellular interactions that can facilitate future studies on neuroinflammation, particularly in the context of neurodegeneration and AD.