CD10 expression identifies a subset of human perivascular progenitor cells with high proliferation and calcification potentials

Abstract

Abstract The tunica adventitia ensheathes arteries and veins and contains presumptive mesenchymal stem cells (MSCs) involved in vascular remodeling. We show here that a subset of human adventitial cells express the CD10/CALLA cell surface metalloprotease. Both CD10+ and CD10− adventitial cells displayed phenotypic features of MSCs when expanded in culture. However, CD10+ adventitial cells exhibited higher proliferation, clonogenic and osteogenic potentials in comparison to their CD10− counterparts. CD10+ adventitial cells increased expression of the cell cycle protein CCND2 via ERK1/2 signaling and osteoblastogenic gene expression via NF-κB signaling. CD10 expression was upregulated in adventitial cells through sonic hedgehog-mediated GLI1 signaling. These results suggest that CD10, which marks rapidly dividing cells in other normal and malignant cell lineages, plays a role in perivascular MSC function and cell fate specification. These findings also point to a role for CD10+ perivascular cells in vascular remodeling and calcification. Significance statement Perivascular adventitial cells include multipotent progenitor cells giving rise in culture to mesenchymal stem/progenitor cells. The present data show that a subset of human adventitial cells natively express the CD10 surface marker, regulated by sonic hedgehog/GLI1 signaling. Purified CD10+ adventitial cells exhibit high proliferative, clonogenic and osteogenic potentials, suggesting a role in pathologic vascular remodeling.