Dendritic cells (DC) are specialized cells that capture and present antigen to T cells. Recent advances have been made in understanding their origin, heterogeneity, and the signals that induce their migration and maturation resident microglia are antigen-presenting cells (APC) involved in stimulation or reactivation of CNS-targeted T cells. Generation of DC from microglia, as demonstrated ex vivo, may support GM-CSF-driven differentiation of brain DC from local, likely, microglial progenitors. Here, we report the establishment of long-term cultures of rat ecto-mesenchymal stem cells (EMSCs) using specific supplemented media for induction. These EMSCs share some morphological characteristics and the allostimulatory capacity of classical DCs, and when transplanted into the brain using a rat glioma model survive within the cortex, and are morphologically and phenotypically similar to microglia over 7 days. Our findings related to the development and differentiation of microglial progenitors support the view that microglia are derived prenatally from mesodermal progenitors that are distinct from monocytes.