Despite adequate reperfusion, however, most patients still suffer irreversible myocardial cell loss.
Ironically, reperfusion itself is an important contributor to irreversible myocardial tissue loss due to accelerated apoptosis, a phenomenon referred to as reperfusion injury ().
Recent developments in stem cell biology have indicated that stem cells can limit the progression of heart failure and restore cardiac tissue mass ().In both experimental and preliminary clinical studies, potential therapeutic benefits of stem cell transplantation have been demonstrated (Menasche et al., 2003, Perin et al., 2003, Shake et al., 2002 and Strauer et al., 2002).Among the stem cells that have been tested for cardiac repair, mesenchymal stem cells (MSCs) derived from adult bone marrow have emerged as one of the most promising stem cell types for treating cardiovascular disease ().Although paracrine effects of mesenchymal stem cells (MSCs) have been suggested previously, cardioprotection by human MSC secretions has never been demonstrated.Human MSC-conditioned medium (CM) was collected by following a clinically compliant protocol.
In a porcine model of ischemia and reperfusion injury, intravenous and intracoronary MSC-CM treatment significantly reduced myocardial nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2′-deoxyguanosine.In addition, expression levels of phospho-SMAD2 and active caspase 3 were diminished following CM treatment, suggesting that TGF-β signaling and apoptosis were reduced.This was associated with a 60% reduction in infarct size and marked improvement of systolic and diastolic cardiac performance as assessed with echocardiography and pressure volume loops.Fractionation studies revealed that only the fraction of the CM containing products 1000 k Da (100–220 nm) provided cardioprotection in a mouse model of ischemia and reperfusion injury.This indicates that the responsible paracrine factor of human MSCs is likely a large complex rather than a single small molecule.These data identify human MSC-CM as a promising therapeutic option to reduce myocardial infarct size in patients with acute MI and suggest that the use of stem cell secretions could extend the applicability of stem cells for therapeutic purposes.).