Context dependent cytokine secretion by stem cell derived microglia in vitro

This thesis demonstrated that inflammation by brain immune called microglia, is context dependent. Previous studies have used microglia derived from human embryonic stem cells to model Alzheimer's disease, but have not investigated whether the responses are uniform across models. This thesis used stem cell-derived microglia, under multiple culture conditions, to demonstrate that differences in inflammation is due to environmental context. It was clearly demonstrated that microglia grown with neurons were more inflammatory than microglia grown alone. Additionally, this thesis shows the inflammation profile is altered by how inflammation is stimulated. This is the first study to demonstrate clear context dependent differences in stem cell-derived microglia inflammation models. This indicates future works should take care to choose appropriate culturing conditions and stimulus choices for modelling diseases of the brain for optimal experimental outcomes.