Vascular smooth muscle progenitor cells: building and repairing blood vessels

Abstract

Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair, and progression of age-related disorders. Defects in these pathways produce malformations of developing blood vessels, depletion of smooth muscle progenitor cell pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular smooth muscle cell precursors is essential if we are to use advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall.

Figure 1. Development of vascular smooth muscle from embryonic progenitors

(a) Vasculogenesis: Vascular development begins when angioblasts differentiate into endothelial cells (red) that self-assemble into a nascent capillary-like vascular network. (b) Investment: Increasing cardiac output from the developing heart stimulates production of mesenchymal cell chemoattractants by endothelial cells. SMC progenitors (brown) begin to invest the vessel wall around E10.5 in the mouse. Close contact with endothelial cells initiates SMC differentiation (blue cells). The position of the vessel within the embryo determines what type of SMC progenitor will be involved in producing the tunica media. Proliferation of SMC progenitor cells is required to supply numbers of SMCs sufficient for continued vascular development. (c) Differentiation and maturation: As layers of SMCs are added to the developing artery wall, a cross-linked extracellular matrix is formed that defines the structure of the mature tunica media.

Figure 2. Sources of vascular smooth muscle progenitor cells in adults

In large arteries (red) and veins (grey), resident SMC progenitors have been identified in the adventitial layer (green cell clusters) ^,, and in the medial layer (scattered blue cells) . Some reports suggest that SMCs in atherosclerotic plaques and intimal masses can arise from circulating, bone marrow-derived progenitor cells (yellow) ^, while others report finding no evidence to support that possible origin ^,. In microvessels, pericytes (purple) have been proposed to have multilineage differentiation potentials ^,, and can act as SMC progenitor cells ^,.