Differentiation of the pericyte in wound healing: The precursor, the process, and the role of the vascular endothelial cell.

Pericytes play a crucial role in the homeostasis and maturation of newly formed vessels, but their precursor and the process of their differentiation remain unclear. In this study, we show that in vivo, pericytes in human granulation tissue taken from burn patients expressed CD13 and collagen I, which are cell markers of peripheral blood fibrocytes (PBFCs). Mouse PBFCs, ex vivo labeled by PKH-26 and administered intravenously back to mice, formed lumens in the granulation tissue and expressed pericyte marker NG2. Furthermore, in cell culture, human PBFCs in co-culture with human umbilical vascular endothelial cells or human dermal microvascular endothelial cells (HDMECs) expressed pericyte markers desmin and myosin heavy chain of smooth muscle cell, and some migrated to the membrane of human umbilical vascular endothelial cells or HDMECs to form PBFC/vascular endothelial cell clusters, or formed round PBFC only clusters with their nuclei aligned along a circle. The formation of PBFC/vascular endothelial cell clusters and round PBFC clusters were inhibited by an antibody against monocyte chemotactic protein-1. PBFCs cultured with homogenate of granulation tissue also expressed desmin and myosin heavy chain of smooth muscle cell. Our findings support that the PBFC is a precursor of pericytes, the differentiation of PBFCs is induced by vascular endothelial cells in a paracrine fashion.