Neuroprotection and neurogenesis by brain vascular pericytes

Abstract

Vascular pericytes (PCs) are a component of the blood-brain barrier (BBB)/neurovascular unit together with astrocytes and endothelial cells. Besides their crucial role in maintaining the BBB, increasing evidence shows that PCs have a potential to be a multipotent stem cell activity. However, their multipotency has not been considered in the pathological brain, such as after an ischemic stroke. Here, we examined whether brain vascular PCs undergoing ischemia (iPCs) have multipotential stem cell activity and differentiate into neural and vascular lineage cells to reconstruct the BBB/neurovascular unit. Using PCs extracted from ischemic regions (iPCs) from mouse brains and human brain PCs cultured under oxygen/glucose deprivation, we show that PCs developed stemness presumably through reprogramming. The iPCs revealed a complex phenotype of angioblasts, in addition to their original mesenchymal properties, and multidifferentiated into cells from both a neural and vascular lineage. These data indicate that under ischemic/hypoxic conditions, PCs can acquire multipotential stem cell activity and can differentiate into major components of the BBB/neurovascular unit. Thus, these findings support the novel concept that iPCs can contribute to both neurogenesis and vasculogenesis (neurovasculogenesis) at the site of brain injuries.