Analysis of differentiation, plasticity and biological activity of human endothelian progenitor cells (HEPC): insights from epigenetic assessment and clinical applications

Despite advances in the management of CVDs, they continue to be a major medical problem in western countries. Current pharmacologic and interventional strategies fail to regenerate dead myocardium and are often insufficient to avoid ventricular remodelling. In this context cell therapy is emerging, and in particular stem cell therapy, due to the great potential of these cells. In this framework we attempted to provide a contribution in three main issues relative to EPC therapy: 1) We established standard operating procedures (SOPs) to purify human CB CD133+ cells using CliniMACS and applied these procedures to obtain BM-derived CD133 cells for an ongoing clinical trial in patients with chronic cardiac ischemia. 2) We assessed the effect of VPA, a chromatin remodelling agent, to improve human CD34+ cells repair potential in a context of acute myocardial ischemia. Our data showed that VPA-treated cells have an improved myocardial protection ability through epigenetic regulated enhancement of stem cell self renewal capacity. 3) We studied the biological properties of mobilized EPCs in a clinical trial that was designed to evaluate the effect of G-CSF as a non-invasive cell delivery strategy in AMI patients. Our trial suggests that in a specific subgroup of patients, early administration (<12 hours) of high-dose G-CSF may attenuate 6-months unfavourable remodelling. This occurred despite the biological function of the mobilized progenitors was depressed likely due to G-CSF effects on EPC clonogenic activity.