Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications

Pericytes are mural vascular cells found predominantly on the abluminal wall of capillaries, where they contribute to the maintenance of capillary structural integrity and vascular permeability. Generally quiescent cells in the adult, pericyte activation and proliferation occur during both physiological and pathological vascular and tissue remodeling. A considerable body of research indicates that pericytes possess attributes of a multipotent adult stem cell, as they are capable of self-renewal as well as commitment and differentiation into multiple lineages. However, pericytes also display phenotypic heterogeneity and recent studies indicate that lineage potential differs between pericyte subpopulations. While numerous microenvironmental cues and cell signaling pathways are known to regulate pericyte functions, the roles that metabolic pathways play in pericyte quiescence, self-renewal or differentiation have been given limited consideration to date. This review will summarize existing data regarding pericyte metabolism and will discuss the coupling of signal pathways to shifts in metabolic pathway preferences that ultimately regulate pericyte quiescence, self-renewal and trans-differentiation. The association between dysregulated metabolic processes and development of pericyte pathologies will be highlighted. Despite ongoing debate regarding pericyte classification and their functional capacity for trans-differentiation in vivo, pericytes are increasingly exploited as a cell therapy tool to promote tissue healing and regeneration. Ultimately, the efficacy of therapeutic approaches hinges on the capacity to effectively control/optimize the fate of the implanted pericytes. Thus, we will identify knowledge gaps that need to be addressed to more effectively harness the opportunity for therapeutic manipulation of pericytes to control pathological outcomes in tissue remodeling.