Editors' ChoiceRegenerative Medicine

Growing a New Heart from the Old One

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Science Translational Medicine  17 Dec 2014:
Vol. 6, Issue 267, pp. 267ec217
DOI: 10.1126/scitranslmed.aaa3462

With the high rates of heart disease in the United States, one could expect to regularly hear a variation of the Tin Man’s musical lament: “If I only had a new heart.” Indeed, heart attack affects ~3% of Americans over the age of 20, and once present, the resulting scarring of the heart is irreversible and can lead to heart failure, dangerous arrhythmias, and death. Regeneration of new heart muscle has long been sought as a solution, but progress has been slow. Many prior efforts have centered on coaxing stem or progenitor cells to differentiate into new cardiac myocytes. But in a new approach, O’Meara et al. identify possible mechanisms by which mammalian cardiac myocytes can reenter the cell cycle and replicate directly.

Currently, the only treatment for patients with severe heart-muscle damage is heart transplantation or implantation of mechanical assist pumps, both of which confer considerable health risks and high financial costs. In their innovative new work, investigators used an unusual mammalian model of myocardial regeneration to study reentry of heart cells into the cell cycle. Until one week of age, neonatal mouse hearts can fully regenerate after resection of the left ventricular apex. On the basis of genetic fate mapping studies, this phenomenon has been attributed to the division of existing cardiac myocytes. O’Meara et al. performed a detailed evaluation of changes in gene expression associated with regeneration of myocytes in neonatal mouse hearts. By comparing these data with genetic data from myocytes in tissue culture and in nonregenerating heart tissue, the authors identified genes potentially involved in cardiac regeneration. They then used computer modeling to predict upstream regulators of these genes and identified the most likely candidates on the basis of their demonstrated ability to promote myocardial DNA synthesis. The gene networks identified as important for neonatal mouse heart regeneration have known functions in cell cycling, mitosis, and RNA processing.

The work by O’Meara et al. has important translational implications. If promoters of cardiac myocyte regeneration can be successfully tested in vivo, therapies could be designed to promote the reversal of otherwise progressive heart damage. Such therapies could improve patient outcomes and add important new tools for the management of heart disease.

C. O’Meara et al., Transcriptional reversion of cardiac myocyte fate during mammalian cardiac regeneration. Circ. Res. 10.1161/CIRCRESAHA.116.304269 (2014). [Abstract]

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