Modeling neuro-immune interactions using human pluripotent stem cells

Human pluripotent stem cells can be differentiated into cell types that are representative of the central nervous system. Under specific culture conditions, these cells can be induced to self-organize into 3D organoids that are reminiscent of the developing brain. Microglia are the resident immune cells of the brain but are derived from a different lineage than neural cells, which presents a challenge to modeling neuroimmune interactions. Although human microglia-like cells can be differentiated from pluripotent stem cells, important considerations include ensuring the identity of microglia, which can be influenced by both the lineage and the local environment, and developing culture methods that promote the integration and survival of diverse cell types in a physiologically relevant model. Recently, several strategies to generate neural organoids with integrated microglia have been demonstrated and provide new opportunities to interrogate interactions among microglia and neurons during development and in response to injury and disease.