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The adventitia is composed of a heterogeneous population of cells, including quiescent resident inflammatory cells, endothelial cells, pericytes, fibroblasts, and recent findings that the abundant presence of resident stem/progenitor cells have been also reported in the layer.1 The adventitia also contains a vasa vasorum, a complete vascular tree–like structure,2 including arterioles, capillaries, and veins. The vascular adventitia acts as a biological processing center for the retrieval, integration, storage, and release of key regulators for the vessel wall function.3 In the adventitia of apoE-deficient mice, stem/progenitor cells expressing Sca1 have been identified, which may contribute to endothelial regeneration and smooth muscle accumulation in the neointimal lesions.4 Several groups5 also demonstrated that the adventitia of human vessels contains stem/progenitor cells with mesenchymal properties because they express vimentin, collagen-I, CD29, CD44, and CD105 and show adipogenic and osteogenic differentiation potential. In addition, it was shown that CD34+/CD31− cells from the adventitia of human saphenous vein gave rise to a proliferative cell population with multilineage potential. In vivo these cells improved neovascularization after they were injected intramuscularly into murine ischemic limbs. Similarly, human aortic CD105+CD34−Flk-1+ cells displayed vasculogenic potential. Thus, adult arteries contain cells with characteristics of ancestral stem cells. Local Sca1+ myeloid progenitors with hematopoietic potential and residing in a similar adventitial niche6 were also identified. These results uncover the complexity of vascular stem cells, which could be closely related to vascular repair and disease development.5 However, little is known about the origins of these stem/progenitor cells in the adventitia.Article, see p 296 In this issue of Circulation Research , Majesky et al7 provided the first direct in vivo evidence that a proportion of Sca1+ progenitors can be …

Vascular Progenitors and Smooth Muscle Cells Chicken and Egg?