The adventitia: a progenitor cell niche for the vessel wall - PubMed (original) (raw)
Review
The adventitia: a progenitor cell niche for the vessel wall
Mark W Majesky et al. Cells Tissues Organs. 2012.
Abstract
Recent observations suggest that the adventitial layer of blood vessels exhibits properties resembling a stem/progenitor cell niche. Progenitor cells have been isolated from the adventitia of both murine and human blood vessels with the potential to form endothelial cells, mural cells, osteogenic cells, and adipocytes. These progenitors appear to cluster at or near the border zone between the outer media and inner adventitia. In the mouse, this border zone region corresponds to a localized site of sonic hedgehog signaling in the artery wall. This brief review will discuss the emerging evidence that the tunica adventitia may provide a niche-like signaling environment for resident progenitor cells and will address the role of the adventitia in growth, remodeling, and repair of the artery wall.
Copyright © 2011 S. Karger AG, Basel.
Figures
Fig. 1
The adventitia. Schematic view of a large elastic artery in cross section showing organization of the major cell types into layers around a central lumen (top). Int = Intima; Med = media; Adv = adventitia. A segment of the vessel wall (inset) is expanded to show the constituent cell types in the normal, uninjured arterial adventitia (bottom). The left side shows a histological cross section of postnatal day 2 thoracic aorta from a Ptc1-LacZ transgenic mouse stained with nuclear fast red. Note that Shh signaling, as indicated by Ptc1-LacZ activity (blue), is confined to the adventitial layer. The right side shows a false color rendering of the same tissue shown at left depicting CD68+ cells (macrophages, orange), Sca1+ progenitor cells (red), adventitial fibroblasts (green), and T cells (purple). Also present in variable numbers are perivascular nerves and associated glial cells, microvessels of the vasa vasorum network, and adipocytes (see also fig. 2).
Fig. 2
The adventitia as a progenitor cell niche in the artery wall. a The left common carotid artery from a postnatal day 9 mouse was fixed and immunostained for Sca1 expression and examined by confocal microscopy. Shown is a reconstructed low power image of stacked Z-plane confocal images of adventitial Sca1+ progenitor cells. Inset A high power view of the characteristic cluster arrangement of Sca1+ progenitor cells in the mouse carotid artery adventitia. b Schematic representation of a proposed progenitor cell niche in the arterial adventitia. We propose that this niche environment contains soluble factors (orange spheres) including Shh [Passman et al., 2008] and other secreted factors not yet described, and ECM proteins (thin brown, grey and white lines) including various collagens, proteoglycans, and hyaluronic acid. Adventitial progenitor cells will possess matrix adhesion receptors (Y) and cell surface receptors for soluble factors (U) that together signal maintenance of a progenitor phenotype, promote survival of progenitor cells, and prevent their premature differentiation. Upon injury to the artery wall, an influx of inflammatory cells into the adventitia likely directs downregulation of niche signaling leading to differentiation of progenitor cells to form SMCs, pericytes, and possibly other vascular cell types.
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