Abstract 796: In Humans, Mesenchymal Stem Cells (MSCs) are Mobilized into the Peripheral Blood Immediately after an Acute Myocardial Infarction (AMI).
It has been shown that Hematopoietic Stem Cells (HSCs) and Endothelial Progenitor Cells (EPCs) are mobilized in humans immediately after an AMI and that they are an effective cell source to be employed in cardiac regenerative medicine. In murine models MSCs have been successfully utilized in cardiac cell therapy, but it is still unknown whether these cells are recruited to the PB immediately after an AMI. Objectives To identify: 1. whether cells with a MSC immunophenotype are mobilized into the peripheral blood (PB) of patients following an AMI; 2. which plasmatic cytokines are correlated to MSC mobilization level; 3. whether MSC mobilization ceases during the chronic phase of an healed infarct. Materials and Methods We enrolled 52 patients with first AMI admission at CCU within 24 hours from the onset of symptoms (mean age, 66 years; 37 men and 15 women) and 15 control subjects (mean age, 55 years; 10 men and 5 women). MSC, HSC and EPC classes were quantified on days 1 (T1), 7 (T2) and six month (T3) after the acute event. Peripheral white blood cells were stained with directly conjugated antibodies and analyzed by FACS. MSCs were identified as CD90+C45/ CD34−/low, CD105+C45/CD34−/low, HSCs as CD90+C45/CD34high, CD105+C45/CD34high, CD117+C45/CD34high, CD133+C45/CD34high and EPCs as VE-cadherin+CD117+/−, CD34+KDR+. The temporal kinetic of SDF-1, IL8, VEGF, SCF, PDGF-BB, bFGF and HGF plasmatic levels was determined by ELISA. Results and conclusion Increased circulating level of MSCs could be documented in the PB of patients suffering from an AMI. Remarkably, MSCs were massively recruited to the PB at T1 (7000 fold with respect to control, P<0.01), persisted at a high concentration at T2 and decreased at control levels (CL) at T3. HSCs and EPcs increased but at much lower extent: HSC increased 40 folds (P<0.01) at T1, nearly doubled in concentration at T2 and decreased at T3; circulating EPCs peaked at T1 (6 folds), decreasing again at T2 and reaching CL at T3. The temporal MSC kinetic strictly overlapped PDGF-BB, HGF and bFGF plasmatic levels. In conclusion, for the first time in humans it has been shown that MSCs are massively recruited into the PB after an AMI. PDGF-BB, bFGF and HGF seem to play a role in this process.