Perspectives of Stem Cell-Derived Microglia for Medicine

Abstract

Microglia, the resident immune cells of the central nervous system (CNS), are responsible for the innate brain immune defence. The exact origin of microglia is still unclear, but several reports suggest that microglia are of myeloid origin (Chan et al., 2007). They appear for the first time at an early embryonic state in the neuroepithelium and populate the brain from the blood in a second perinatal phase. Under pathological conditions or infections, microglia migrate to the affected tissue. On site, they change their phenotype to a proinflammatory cell type, release cytotoxic molecules such as reactive oxygen species to fight against microbes or clear tissue debris after sterile injury. Microglia also phagocyte oncogenically transformed brain cells and are able to activate additional immune cells. Proinflammatory microglial cells are also involved in the progression of neurodegenerative diseases. Research on microglia is mainly performed on primary cells. However, only a limited amount of murine or human microglial cells can be obtained from the brain tissue, thus complicating investigations of drug screenings or new cell therapy approaches that are requiring a high number of cells. For this reason, stem cell-derived microglia represent a useful tool for further studies to elucidate the role of microglia in diseases and therapeutical approaches. Data from others and our laboratory show that microglial precursor cell lines can be obtained from mouse embryonic stem cells or human induced pluripotent stem cells via a neural differentiation protocol. Human microglial cell lines open new alternatives for drug screening, combating cancer and regenerative approaches for neurological diseases.