Regeneration of the heart.
Bottom Line: First, although endogenous mammalian cardiac regeneration clearly seems to decline rapidly after birth, it may still persist in adulthood.Second, recent breakthroughs have enabled reprogramming of cells that were apparently terminally differentiated, either by dedifferentiation into pluripotent stem cells or by transdifferentiation into cardiac myocytes.In this review, we discuss the current status of research on cardiac regeneration, with a focus on the challenges that hold back therapeutic development.
Affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Partners Research Building, Cambridge, MA, USA. firstname.lastname@example.orgShow MeSH
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Mentions: The heart also presents a unique challenge compared to other organs owing to the propensity of cardiac myocytes to synthesize DNA during S-phase without completing either mitosis and/or cytokinesis (Fig 1). During early post-natal development, for example, the majority of rodent cardiac myocytes (Li et al, 1996) and an estimated 25–57% of human cardiac myocytes (Olivetti et al, 1996; Schmid & Pfitzer, 1985) become binucleated. By adulthood, most cardiac myocyte nuclei have also become polyploid with at least one (4n: tetraploid) or two (8n: octoploid) additional rounds of chromosomal replication (Bergmann et al, 2010). Although some studies demonstrated that the polyploidy rate in the cardiac myocyte pool is not affected by ageing or injury (Olivetti et al, 1996), others suggested that the ploidy state is more dynamic. The ploidy state of cardiac myocytes may increase with myocardial hypertrophy or injury (Adler & Friedburg, 1986), which could be mistaken for myocyte division. Conversely, hearts that have been unloaded by implantation of a ventricular assist device may have a lower percentage of polyploid myocytes, because more 2n cardiac myocytes are being generated (Wohlschlaeger et al, 2010). These aspects of cardiac myocyte biology inevitably represent potential confounders that must be considered in any quantification of cardiac myocyte formation. As with any controversial hypothesis, achieving consensus regarding adult mammalian cardiac myocyte turnover will likely require multiple lines of evidence using multiple different methodologies.
Affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Partners Research Building, Cambridge, MA, USA. email@example.com