Endothelial progenitor cells transfected with PDGF: cellular and molecular targets for prevention of diabetic microangiopathy.

Microvascular insufficiency represents a major cause of end-organ failure among diabetics. Prevention at early stage of disease is therefore necessary and is a focus of current investigations. Progression of diabetes is complicated by endothelial cell apoptosis as well as occlusion of arteriole and capillary leading to microvascular rarefaction. This favors the formation of non-healing limb ulcers and limits the benefit of revascularization. Recent study indicated that reduction of platelet derived growth factor (PDGF) expression was indeed critical, in causing functional and morphological vascular changes, namely the dissociation of pericytes from the capillaries in muscles. Diabetic microangiopathy is a result of pericytes dissociation from reduced PDGF as well as vessel rarefaction from reduced number of endothelial progenitor cells (EPCs) and EPC dysfunction. Since blood vessels develop through the assembly of these two principal cell types--endothelial cells and pericytes/smooth muscle cells, prevention of diabetic microangiopathy requires interventions targeting at both cell types in a complementary and synergistic manner. An improved recruitment of EPCs will help repair of injured endothelium while molecular targeting with PDGF will enhance pericytes recruitment. EPCs modified with PDGF therefore hold promise as the next generation of agents for prevention of microangiopathy.