Endothelial Progenitor Cells and the Diabetic Paradox Current Knowledge and Therapeutic Perspectives

The discovery of postnatal vasculogenesis and of the important roles played by bone marrow-derived Endothelial Progenitor Cells was a landmark in vascular biology that forever has changed the concept of neovascularization. Diabetes associated vascular complications involve distinct modifications in neovascular formation, which is reduced in cardiovascular disease and increased in diabetic retinopathy, defining the diabetic paradox. The vasculogenic process seems to play a central dual role in these alterations: by one side dysfunctional EPCs impair endothelial regeneration in peripheral vasculopathy and on the other hand alterations in EPCs are involved in increased retinal vessel growth in diabetic retinopathy. Although still under investigation, these divergent features seem related to a differential response of progenitor cells to ischemic-induced depletion/induction of angiogenic factors. Due to the importance of vasculogenesis, therapeutic interventions targeting EPCs in diabetic vascular complications arose as a potential tool. However, scarce information has been disclosed regarding the safety and harmful side effects of these therapies. Future research is mandatory in order to further elucidate the complex mechanisms governing the diabetic- vasculogenic paradigm, bringing also novel insights into the potential therapeutic usefulness of EPCs.