Overall, these results underscore the potential of iMGLs as a renewable source of patient-derived microglial-like cells for studying the role of microglia in neurodegenerative diseases. While our comparisons were limited to cultured microglia, we showed that our cells were highly similar to primary cells and our studies have highlighted potential new ways to culture microglia within BORGs or mouse brains. For example, transplantation of iMGLs into various CNS disease mouse models will allow for the study of human microglial function in neurodegenerative disease in vivo that may be influenced by genetics and the inheritance of specific mutations. This platform will allow for the identification of potential novel microglial-based translational therapies, as recently discussed (Biber et al., 2016). Finally, while technical challenges exist for isolating microglia from both human brain and BORGS for study, the development of future tools will likely make it feasible to compare microglia isolated from BORGs with freshly isolated microglia to determine whether 3D organoid systems fully recapitulate the in vivo microglia signature. In summary, we demonstrate a methodology to generate human microglial-like cells, in large quantities, from renewable iPSCs that can be used as primary microglia surrogates.
