myocardial infarction and chronic ischemicreperfusion and stenting of the respective coronary artery as well as anti-thrombotic therapies. These therapies cannot avoid the later sequelae of the disease, namely ventricular remodelling. Since the human heart only has very limited ability to regenerate itself it can normally not compensate for the consequences of an acute myocardial infarction, namely tissue damage in the affected region of the heart and massive cell death due to oxygen deprivation. For both, acute myocardial infarction and chronic ischemic heart diseases, this leads to an increased morbidity and mortality for patients. The goal is to increase cardiac regeneration on top of standard therapies, to improve ventricular function and to increase the number of viable and functional cells in the diseased cardiac tissue, thereby ameliorating the effects of cardiac remodelling with the long term goal of reducing morbidity and mortality of patients with large myocardial infarctions and depressed left ventricular contractile function.
The mechanism of action of BMCs
One route might be that they either differentiate into endothelial cells and become incorporated perivascularly to support neovascularization of the ischemic tissue. Another route might be that the BMCs transdifferentiate into cardiomyocytes or fuse with existing cardiomyocytes and thus increase cardiac muscle tissue. The third route might be an indirect one whereby the BMCs would produce paracrine factors recruiting other cells and enhancing neovascularization and arteriogenesis in the ischemic area. There is an intense ongoing debate in the scientific community about these alternative mechanisms of action. Albeit there is overwhelming evidence in the literature that BMCs ameliorate the effects of cardiac ischemia, it is not yet clear, whether any of the three potential BMC fates (neovascularization, transdifferentiation or paracrine effects) is the major driver of cardiac repair or whether all three routes contribute to the final outcome.