A Nucleolar Weapon in Our Fight for Regenerating Adult Hearts

Abstract

See related article, pages 89–97 Ischemic diseases and heart failure remain the major causes of morbidity and mortality in the industrialized world. Several new therapeutic modalities have been developed to interfere with the response to injury and to improve cardiac function after ischemia or cardiomyopathy. Experimental and clinical studies demonstrated that the transplantation of bone marrow–derived or tissue-resident stem/progenitor cells in diseased hearts improves neovascularization and functional recovery.1 However, the recent discovery of cardiac stem cells (CSCs) in the adult heart poses the question whether activation of the endogenous pool of these resident stem cells may compensate for the loss of cardiac tissue after injury and improve functional recovery. Indeed, a genetic fate-mapping study elegantly demonstrated that stem cells or precursor cells significantly contributed to the replacement of adult mammalian cardiomyocytes after injury.2 Although it remains unclear to what extent cardiac regeneration in this genetic model was mediated by CSCs or circulating progenitor cell populations being attracted to the heart after injury, mounting evidence suggests that injury-associated signals activate CSCs in situ, which subsequently contribute to the refreshment of the injured heart.3 Obviously, to play a significant role in endogenous cardiac regeneration, the relatively small number of endogenous CSCs needs to be expanded after injury before differentiating into cardiac myocytes. However, the molecular mechanisms underlying the activation, expansion, and recruitment of resident CSCs after injury remain unclear. In the current issue of Circulation Research , Siddiqi et al provide an intriguing concept, which might help to mechanistically explain how proliferation of CSCs is regulated in response to injury.4 The authors investigated the cardiac expression of stem cell specific genes, involved in self-renewal and proliferation, during cardiomyopathic injuries and found increased expression of the nucleolar protein nucleostemin—recently discovered in embryonic and adult stem cells as well …