Shedding New Light on the Mechanism Underlying Stem Cell Therapy for the Heart

Abstract

It is widely accepted that the adult mammalian heart is a terminally differentiated organ with little capacity to regenerate after damage, such as that caused by a myocardial infarction (MI). Nevertheless, mounting evidence suggests that mature cardiomyocytes do slowly turn over (up to 1% per year).1,2 In addition, there are many claims that the heart contains cell populations expressing stem cell markers that could in principle contribute to repair.3,4 However, whether proliferating cardiomyocytes or endogenous stem or progenitor cells actually contribute to cardiac repair after injury has remained unclear – until now. In a study recently published in Cell Stem Cell,5 Lee and colleagues used a clever lineage-tracing approach in mice1 to identify two potential sources of new cardiomyocytes in the adult heart: those arising from the division of existing cardiomyocytes and those formed by differentiation of the endogenous progenitors. Using their transgenic mouse model, they were able to distinguish these two sources of cardiomyocytes. More strikingly, the authors show that some stem cells currently being tested for the ability to improve heart function in cell transplantation trials can enhance the differentiation of endogenous progenitors, whereas others cannot. The study provides new insight into how cell therapy for the heart might work and suggests ways in which optimal cell types for therapy might be chosen – as well as how the controversial outcomes of many clinical trials might be resolved.