On the Fabric of the Human Body

With the publication of De Humani Corporis Fabrica in 1543, Andreas Vesalius bestowed some of the greatest advancements of anatomic understanding since the time of Galen, correcting major misconceptions, eg, the notion that the great vessels originated in the liver. It took nearly 1500 years for this evolution in anatomic thinking to transpire.It is simultaneously humbling and invigorating to note that nearly 500 years later the study of anatomy is just as lively and full of evolutionary change. In this issue of Circulation , Kajstura and colleagues1 definitively dispatch the dogma of the heart as a terminally differentiated organ, a concept formulated a mere 40 years earlier, and in so doing completely recalibrate our understanding of cellular homeostasis in the healthy and diseased heart.Article see p 1869In 1973, Radovan Zak2 of the University of Chicago stated unequivocally, “The adult heart enlarges only by enlargement of its component muscle cells. Division of ventricular muscle cells in mammals is not activated after cardiac injury.” This conclusion was largely consistent with work by Linzbach3 in 1960; however, in this earlier comprehensive histological analysis, there was a suggestion that under certain circumstances the number of cardiac muscle fibers might increase.The Anversa laboratory began suggesting the possibility of cardiomyocyte proliferation in 1980,4 and by 1992, the group began to document clear evidence for replication of cardiac muscle cells in response to physiological stress and myocardial injury in both experimental models5–8 and humans.9,10 These early works included such bold statements as “the recognition of factors controlling myocyte proliferation may provide a new approach for regeneration of damaged and lost myocardium, a phenomenon considered impossible for several decades.” Although some recognized the power and implications of these observations, the Pfeffers' call for open-mindedness …