New vessel formation in the context of cardiomyocyte regeneration – the role and importance of an adequate perfusing vasculature

•Adequate arterial perfusion is essential for proper cardiomyocyte function.•Clinical data has shown that only large conduit vessels are adequate for this task.•So far, few cell therapy studies have addressed this need during cardiac repair.•Of these, some studies have shown the generation of small-medium sized vessels.•The provision of a robust cardiac arterial supply is a key area for future study.

The history of revascularization for cardiac ischemia dates back to the early 1960’s when the first coronary artery bypass graft procedures were performed in humans. With this 50 year history of providing a new vasculature to ischemic and hibernating myocardium, a profound depth of experience has been amassed in clinical cardiovascular medicine as to what does, and does not work in the context of cardiac revascularization, alleviating ischemia and adequacy of myocardial perfusion. These issues are of central relevance to contemporary cell-based cardiac regenerative approaches. While the cardiovascular cell therapy field is surging forward on many exciting fronts, several well accepted clinical axioms related to the cardiac arterial supply appear to be almost overlooked by some of our current basic conceptual and experimental cell therapy paradigms. We present here information drawn from five decades of the clinical revascularization experience, review relevant new data on vascular formation via cell therapy, and put forward the case that for optimal cell-based cardiac regeneration due attention must be paid to providing an adequate vascular supply.