LAUSR

Modern reperfusion treatment for the early stages of acute myocardial infarction, which is really quite miraculous, if you pause to think about it, arose from a fundamental understanding of coronary thrombosis. Might we someday also be able to restore function for patients who come in days, or even years, after a myocardial infarction? If we will ever develop biological treatments that restore cardiac function through tissue regeneration, we need to understand the basics. Thus, how the cardiomyocytes of the heart replenish themselves is more than an academic curiosity, because this fundamental understanding will likely be crucial to building successful regenerative strategies for failing hearts. In this issue of Circulation, 5 groups of investigators tackled the same biological question, and all reached the same conclusion: that cells in the heart expressing the Sca-1 cell surface antigen do not become cardiomyocytes to any meaningful degree and instead become endothelial cells. These articles add to the growing body of evidence that, in adult mammals, our new cardiomyocytes arise from preexisting cardiomyocytes and rarely (if at all) from adult cardiac stem cells.1 However, these new articles do not just provide a piece of the puzzle of myocardial biology; together, the articles also provide perspective on how science advances over time to benefit all of us. To explain this point, it is worth considering how the concept of adult cardiac stem cells began. Adult stem cells are cells that can self-renew and also differentiate to ≥2 different cell types. There are well-established examples of adult stem cells in, for example, the hematopoietic system, the intestinal epithelium, and the hair follicle.2 Approximately 15 years ago, adult stem cells were exciting for all areas of mammalian biology, for good reasons.3 The use of embryonic stem cells was highly controversial on ethical and religious grounds; hence, adult stem cells appeared to be the solution to regenerating human tissues. George Walker Bush was President of the United States, and he supported adult stem cell research but opposed embryonic stem cell research.4 Adult stem cells could potentially be isolated from an existing tissue (possibly even a small biopsy or a sample of blood), expanded, and then used to create unlimited numbers of a patient’s own differentiated cells. No matter what the tissue of interest, investigators wanted to identify and isolate that tissue’s putative endogenous adult stem cells. The concept of resident adult cardiac stem cells was therefore extremely attractive, because isolating and exploiting such a cell could theoretically generate new autologous cells to reconstitute damaged hearts. Every patient could essentially be their own cardiomyocyte donor. The challenge for cardiovascular investigators was finding adult cardiac stem cells; without a cell surface marker to identify the cells, it was like looking for a needle in a haystack without knowing what a needle looks © 2018 American Heart Association, Inc.