Abstract

The use of neural cell types derived from human induced pluripotent stem cells (iPSC) hold promises for filling an important gap between studies in humans and animal models for drug discovery and modeling of neurodegenerative diseases. While protocols to generate pure, highly specialized, and terminally-differentiated cell types (such as neurons, astrocytes, and microglia) from iPSC are available, it is now evident that studying these cells in isolation doesn’t recapitulate the complexity required in a “brain-in-a-dish” model. Therefore, we have established new tri-culture model systems that incorporate iPSC-derived neurons, astrocytes, and microglia together. To balance survival and function of each cell type, optimization of extracellular matrixes (ECM), media, and cell ratios is required. Here we present data from various assays, including microglia phagocytosis, neuroinflammatory cytokine release, and neuronal network activity. These results highlight the importance of the complex interplay among the different cell types in “brain-in-a-dish” in vitro models for the development of novel therapeutics and the mechanistic understanding of different cellular aspects of neurogenerative disease.