Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation

Abstract

Cell-based therapy has emerged as a promising therapeutic tool for treatment of ischemic cardiovascular disease. Both unselected bone marrow-derived mononuclear cells (BMNCs), which include stem/progenitor cells and several other cell types, and endothelial progenitor cells (EPCs), a subpopulation of BMNCs, display regenerative potential in ischemic tissue. Abundant evidence supports the involvement of EPCs in capillary growth, and EPCs also appear to participate in the formation of collateral vessels. Collectively, these effects have led to improved perfusion and functional recovery in animal models of myocardial and peripheral ischemia, and in early clinical trials, the therapeutic administration of EPCs to patients with myocardial infarction or chronic angina has been associated with positive trends in perfusion. EPCs also contribute to endothelial repair and may, consequently, impede the development or progression of arteriosclerosis. This review provides a brief summary of the preclinical and clinical evidence for the role of EPCs in blood-vessel formation and repair during ischemic cardiovascular disease.

Figure 1. EPCs in Ischemic Tissue Repair

The regenerative effects of EPCs in ischemic tissue are currently believed to occur primarily through the release of multiple factors that alter the microenvironment in a paracrine fashion. The secreted factors, in turn, recruit additional stem/progenitor cells, activate resident stem cells, suppress cell death, and may enhance the proliferation of resident cells. Collectively, these effects promote the growth of new blood vessels and improve tissue perfusion.

Figure 2. Mechanisms of Neovascularization

(A) Exceptionally detailed images depict the mechanisms of neovascularization in ischemic cardiovascular disease. (B) In response to the obstruction of bulk blood flow, collateral vessels form via arteriogenesis – the transformation of pre-existing arterioles into larger conduction vessels. (C) In ischemic tissues, capillary formation can occur via both angiogenesis – the sprouting of capillaries from pre-existing vessels – and vasculogenesis – de novo formation in previously avascular tissue, which is stimulated by the recruitment of stem and progenitor cells; the incorporation of EPCs into the microvasculature has been detected via the use of genetically modified cells.