It has been suggested that a vascular-like cell has multipotent regenerative and mesenchymal lineage relationships. The identity of this stem/progenitor cell has remained elusive. We report here that adult central nervous system (CNS) capillaries contain a distinct population of microvascular cells, the pericyte that are nestin/NG2 positive and in response to basic fibroblast growth factor (bFGF) differentiate into cells of neural lineage. In their microvascular location, pericytes express nestin and NG2 proteoglycan. In serum containing media primary (0 to 7 day old) CNS pericytes are nestin positive, NG2 positive, alpha smooth muscle actin (alphaSMA) positive, and do not bind the endothelial cell specific griffonia symplicifolia agglutinin (GSA). In serum containing media, pericytes do not undergo neurogenesis but are induced to express alphaSMA. In bFGF containing media without serum, CNS pericytes form small clusters and multicellular spheres. Differentiated spheres expressed neuronal and glial cell markers. After disruption and serial dilution, differentiated spheres were capable of self-renewal. When differentiated spheres were disrupted and cultured in the presence of serum, multiple adherent cell populations were identified by dual and triple immunocytochemistry. Cells expressing markers characteristic of pericytes, neurons, and glial cells were generated. Many of the cells exhibited dual expression of differentiation markers. With prolonged culture fully differentiated cells of neural lineage were present. Results indicate that adult CNS microvascular pericytes have neural stem cell capability.

Pericytes were described nearly 140 years ago by the French scientist Charles-Marie Benjamin Rouget and were referred to as the Rouget cell. The Rouget cell was renamed primarily due to its anatomical location in the endothelium. Pericytes are important cellular constituents of the capillaries and post capillary venules and are located abluminal to the endothelial cells and luminal to parenchymal cells. They deposit elements of the basal lamina and are totally surrounded by this vascular component. Despite many years of investigation since their discovery, the role of this intriguing cell still remains a mystery, in part, due to the difficulty of studying this cell in vivo, due to the difficulty of isolating pure primary pericytes, and due to the lack of a pericyte specific marker. Pericytes are thought to be local regulatory cells and important to the maintenance of homeostasis and hemostasis. In the brain, pericytes are in active communication with the cells of the neurovascular unit and make fine-tuned regulatory adjustments in response to stress stimuli. These adaptations at the vascular level form the basis for functional and phenotypic changes that include differentiation along mesenchymal and neurological lineages, and lend credence to the supposition that pericytes are multipotential stems cells in the adult brain and in other tissues. This review will consider evidence that pericytes are stem cells derived from historical work and from more recent literature, and will attempt to dispel a number of misconceptions about the pericyte that has lead to confusion in the literature. We will also speculate on the importance of pericyte stem cell activity in survival and DNA repair and how dysregulation of pericyte function may lead to disease.

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Pericytes are a very important cellular constituent of the blood-brain barrier. They play a regulatory role in brain angiogenesis, endothelial cell tight junction formation, blood-brain barrier differentiation, as well as contribute to the microvascular vasodynamic capacity and structural stability. Central nervous system pericytes express macrophage functions and are actively involved in the neuroimmune network operating at the blood-brain barrier. They exhibit unique functional characteristics critical for the pathogenesis of a number of cerebrovascular, neurodegenerative, and neuroimmune diseases.