Model of MAPC interactions
with splenocytes to modulate
microglia/macrophage phenotype. (A) In a normal uninjured brain resident microglia generally exist in a ramified M2 state. Functions include patrolling the brain to detect any disturbances or foreign substances as well as many other functions. This allows for a neuroprotection of neurons and other cell types. Regulatory T-cells (Treg) are in constant communication with the resident ramified microglia (B) After TBI, ramified microglia change into activated microglia, which function mainly to phagocytose cellular debris created after injury. In addition to the activated resident microglia, there is influx of macropahges due to the damaged (leaky) BBB as well as upregulation of chemoattractant molecules and adhesion factors. After injury activated microglia and infiltrating macrophages are indistinguishable from each other. Both these cell types are being modulated by effector T-cells (Teff). (C) After TBI, MAPC treatment helps seal the leaky BBB. In addition, with direct contact with splenocytes, MAPC treatment results in Treg proliferation. This in turn aids in modulating the activated microglia/macrophage into ramified microglia, thereby reducing the long-term proinflammatory effects of activated microglia. BBB, blood brain barrier; MAPC, multipotent adult progenitor cell; TBI, traumatic brain injury.