The promise of myocardial repair--towards a better understanding.

Abstract

Despite major advances in the management of acute myocardial infarction, including effective and early urgent revascularisation, myocardial damage is common and may be severe. In many patients myocardial infarction is followed by myocardial scarring, ventricular remodelling, dilatation and reduced cardiac function followed over a period of months to years by an inexorable downhill course culminating in heart failure and death regardless of best current treatment modalities. In the new millennium, we are witnessing a paradigm shift in our approach to myocardial damage, following the landmark observation that the adult heart is not necessarily a post-mitotic organ and that regeneration of cardiac myocytes may occur in the circumstances of the appropriate signalling processes.1 Within a relatively short time period, the findings from the basic science and animal laboratory have been applied in the clinical arena. Intracoronary injection of mesenchymal stromal cells (MSCs) of bone-marrow origin produced encouraging results in humans recovering from acute infarction,2 with an improvement in myocardial perfusion by thallium-201 scintigraphy, and higher ejection fraction compared with patients not treated. The intracoronary injection of progenitor cells originating in marrow or peripheral blood (PBSCs) was followed by enhanced regional contractile function, a significant increase at 4 months in coronary flow reserve in the infarct artery and a significant increase in myocardial viability by quantitative F-18-fluorodeoxyglucose-positron emission tomography in the infarct zone.3 Ejection fraction increased significantly post-infarction.3 There were no differences for any measured parameter between blood-derived or bone-marrow-derived progenitor cells. Britten et al.4 showed that the migratory capacity of the infused cells is a major determinant of infarct remodelling, disclosing a causal effect of progenitor cell therapy on regeneration enhancement. None of the published studies regarding injection of MSCs or PBSCs have been randomised or placebo-controlled and a large number of questions remain unanswered as …