Classification and Functional Characterization of Vasa Vasorum-Associated Perivascular Progenitor Cells in Human Aorta

In the microcirculation, pericytes are believed to function as mesenchymal stromal cells (MSCs). We hypothesized that the vasa vasorum harbor progenitor cells within the adventitia of human aorta. Pericytes, endothelial progenitor cells, and other cell subpopulations were detected among freshly isolated adventitial cells using flow cytometry. Purified cultured pericytes were enriched for the MSC markers CD105 and CD73 and depleted of the endothelial markers von Willebrand factor and CD31. Cultured pericytes were capable of smooth muscle lineage progression including inducible expression of smooth muscle myosin heavy chain, calponin, and α-smooth muscle actin, and adopted a spindle shape. Pericytes formed spheroids when cultured on Matrigel substrates and peripherally localized with branching endothelial cells in vitro. Our results indicate that the vasa vasorum form a progenitor cell niche distinct from other previously described progenitor populations in human adventitia. These findings could have important implications for understanding the complex pathophysiology of human aortic disease. •Perivascular progenitor cells were classified in human ascending aorta•Adventitial vasa vasorum were identified as a progenitor cell niche•Purified pericytes were functional in vitro as smooth muscle cell progenitors•Branching endothelial cell networks were associated with pericytes in vitro Phillippi and colleagues classified the surface proteome of perivascular progenitor cells in human ascending aorta and revealed their localization to the vasa vasorum. Purified pericytes demonstrated potential for smooth muscle cell differentiation and an association with branching endothelial cells in vitro.