The interplay between the immune and nervous systems is a critical aspect of various neurodegenerative diseases (NDD), but the development of physiologically relevant models mimicking the intercellular interactions remains a challenge. To overcome this, human induced pluripotent stem cell technology can be leveraged to build multicellular models and bring human pathophysiology into preclinical testing to develop new therapeutics targeting neuroinflammation.
In this study, we developed a triculture model with human iPSC-derived neurons, astrocytes and microglia that resembles physiological conditions. This relevant model recapitulates pro-inflammatory cytokines, phagocytic activity, microglia and neural morphological changes, which can be quantified with Ncardia assays. The results indicate that our in vitro models are able to recapitulate neuroinflammation in the context of NDDs such as Alzheimer's Disease, and enable evaluation of compounds' effect in this pathological process. Our model can be utilized to test new therapeutics targeting neuroinflammation, facilitating early decision making steps with high confidence.