Primary adult microglia: a guided approach towards more relevant in vitro methodology

Abstract: Microglia are the resident tissue macrophages of the central nervous system. Recent publications demonstrate the intricate involvement of innate immune responses in the pathogenesis of neurodegenerative disorders, underlining the importance of these cells. The development of in vitro methodology is however hampered by several issues. As most neurodegenerative diseases present themselves at relatively old age it is most relevant to study adult, aged microglia. Rodent adult microglia, stem cell-based and cell line-based approaches are of limited use for such purposes. Primary cell cultures from adult humans or animals with a long life span might be a better option.
We have developed primary microglia cultures from adult rhesus macaques and will present data demonstrating their value for studies on innate immune responses. We have uncovered cell-specific differences in e.g. inflammasome molecular machinery. Since very recent transcriptome studies have demonstrated that classical primary microglia culture models still only partially recapitulate the hallmarks of mature homeostatic microglia we have followed up on these studies. We have determined the transcriptome of mature homeostatic ex vivo microglia from adult rhesus macaques and compared this to the transcriptomes of primary rhesus microglia that were exposed to different experimental cell culture regimes for 7 days. We will also present a brief overview of these results and present new cell culture approaches currently under development in our lab.