Vasculogenic properties of adventitial Sca-1+CD45+ progenitor cells in mice: a potential source of vasa vasorum in atherosclerosis

Abstract

The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.

Single‐cell RNA sequencing reveals the induction of novel myeloid and myeloid‐associated cell populations in visceral fat with long‐term obesity

“…Cluster 5 cells also expressed both Klf4 and Myc genes but did not express Oct4 and Sox2, which suggests these cells possess a fate‐restricted multipotent but not pluripotent phenotype. Described characteristics suggest that the Cluster 5 cells may, in fact, represent hematopoietic‐derived precursor cells that resemble the previously reported monocyte‐predisposed hierarchy of CD45 + progenitor cells located in the adventitia that express c‐kit, CD34, and Ly6a 29,30 . Previous other studies confirmed that murine aorta contains multiple hematoprogenitor/hematopoietic stem cell (hPC/HSC) populations enriched in CD45 + and Ly6a + that represent macrophage precursors.…”

Recent Developments in Vascular Adventitial Pathobiology

“…Adventitial Sca-1 þ CD45 þ cells also possess vasculogenic and angiogenic activities and may thus be a source of VV. 43 Mekala et al 44 demonstrated that fetal liver kinase 1epositive CD34 þ stem cells resident in the vascular adventitia, including that of coronary arteries, are a source for generating mouse and human cardiomyocytes after myocardial infarction. ECs and macrophages support this novel process.…”

The P387 thrombospondin‐4 variant promotes accumulation of macrophages in atherosclerotic lesions

“…Recent studies suggested that adventitia is not only providing structure to a blood vessel but plays an active role in regulation of arterial wall functions and in development of pathological changes associated with wall remodeling, for example, aneurism and atherosclerosis development. 50,51 Adventitia of ApoE -/mice predisposed to development of atherosclerosis has increased myeloid cell infiltration, activated resident macrophages, and enhanced interaction between the mesenchymal cells and inflammatory macrophages. 52 The interaction of resident cells of adventitia with immune cells appears crucial at the early stages of atherosclerosis.…”