Vascular wall resident progenitor cells: a source for postnatal vasculogenesis

Abstract

Here, we report the existence of endothelial precursor (EPC) and stem cells in a distinct zone of the vascular wall that are capable to differentiate into mature endothelial cells, hematopoietic and local immune cells, such as macrophages. This zone has been identified to be localized between smooth muscle and adventitial layer of human adult vascular wall. It predominantly contains CD34-positive (+) but CD31-negative (-) cells, which also express VEGFR2 and TIE2. Only few cells in this zone of the vascular wall are positive for CD45. In a ring assay using the fragments of human internal thoracic artery (HITA), we show here that the CD34 + cells of the HITA-wall form capillary sprouts ex vivo and are apparently recruited for capillary formation by tumor cells. New vessels formed by these vascular wall resident EPCs express markers for angiogenically activated endothelial cells, such as CEACAM1, and also for mature endothelial cells, such as VE-cadherin or occludin. Vascular wall areas containing EPCs are found in large and middle sized arteries and veins of all organs studied here. These data suggest the existence of a 'vasculogenic zone' in the wall of adult human blood vessels, which may serve as a source for progenitor cells for postnatal vasculogenesis, contributing to tumor vascularization and local immune response.

Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches

“…Over the past decade, there has been increasing evidence that the integrity of the vascular wall is maintained by diversified cell populations, dedicated to endothelial repair and angiogenesis [8,9,14,15]. Diabetic patients often show deterioration of those cell types, especially in the presence of other cardiovascular complications [13,16].…”

Working hypothesis to redefine endothelial progenitor cells

“…19 It now appears that aside from angiogenesis and arteriogenesis, circulatory system remodeling in the adult may indeed involve the recruitment of not only endothelial progenitors but also a plurality of cells in an intricate collaboration. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Sprouted endothelium may line the vessel lumen while other cells support vessel formation through secretion of cytokines and modification of the extracellular space. [40][41][42][43][44][45] Although each cell type appears to be fundamentally different, all cell types involved in postnatal vasculogenesis have been lumped into the single term 'EPC'.…”

A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1 + smooth muscle progenitor cells

“…Adventitial cells participate in vascular growth and repair and are important determinants of lumen size via control of inward or outward wall remodeling processes (2,5). Recent studies report unexpected roles for the adventitia insofar as it supports resident progenitor cells that can adopt both vascular and nonvascular fates (6)(7)(8). Despite these important functional properties, the signals and environmental cues that confer such unique and dynamic properties to the adventitial layer remain largely unknown.…”

“…The adventitia responds to balloon catheter injury with rapid increases in SM␣Actin and SM22␣ expression, particularly at the media-adventitia interface (5). Endothelial progenitor cells are reported to cluster between the media and adventitia in human arteries (7,8). These cells formed capillary sprouts in ex vivo ring culture assays and were recruited by tumor cells for capillary vessel formation in vivo.…”