Progenitor cells and vascular disease

Abstract

Vascular progenitor cells have been the focus of much attention in recent years; both from the point of view of their pathophysiological roles and their potential as therapeutic agents. However, there is as yet no definitive description of either endothelial or vascular smooth muscle progenitor cells. Cells with the ability to differentiate into mature endothelial and vascular smooth muscle reportedly reside within a number of different tissues, including bone marrow, spleen, cardiac muscle, skeletal muscle and adipose tissue. Within these niches, vascular progenitor cells remain quiescent, until mobilized in response to injury or disease. Once mobilized, these progenitor cells enter the circulation and migrate to sites of damage, where they contribute to the remodelling process. It is generally perceived that endothelial progenitors are reparative, acting to restore vascular homeostasis, while smooth muscle progenitors contribute to pathological changes. Indeed, the number of circulating endothelial progenitor cells inversely correlates with exposure to cardiovascular risk factors and numbers of animal models and human studies have demonstrated therapeutic roles for endothelial progenitor cells, which can be enhanced by manipulating them to overexpress vasculo-protective genes. It remains to be determined whether smooth muscle progenitor cells, which are less well studied than their endothelial counterparts, can likewise be manipulated to achieve therapeutic benefit. This review outlines our current understanding of endothelial and smooth muscle progenitor cell biology, their roles in vascular disease and their potential as therapeutic agents.

Figure 1

Mobilization, homing and recruitment of vascular progenitor cells. Vascular damage, such as that following vein grafting or stenting, involves endothelial denudation and platelet accumulation. Platelets, along with neighbouring endothelial and smooth muscle cells, secrete various growth factors and cytokines/chemokines, including platelet‐derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and stromal cell‐derived factor‐1 (SDF‐1). PDGF is important for smooth muscle cell migration and proliferation. VEGF and SDF‐1 are important for the mobilization of vascular progenitor cells; circulating in the blood and promoting progenitor cell translocation from the quiescent vascular bone marrow niche. Both endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs) of bone marrow origin have been observed in neo‐intimal lesions. Once mobilized, vascular progenitor cells are believed to migrate through the circulation to the site of damage where chemokines and integrins mediate their recruitment and there is evidence for both luminal and adventitial routes of entry. For illustrative purposes, vascular progenitor cells are shown as a population of c‐kit⁺ cells within the bone marrow, and as EPC and SMPC populations thereafter.