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Published online on August 19, 2003, 10.1073/pnas.1832855100
PNAS | September 2, 2003 | vol. 100 | no. 18 | 10440-10445


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From The Cover
Medical Sciences
Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy

Konrad Urbanek *, Federico Quaini *, Giordano Tasca {dagger}, Daniele Torella *, Clotilde Castaldo *, Bernardo Nadal-Ginard *, Annarosa Leri *, Jan Kajstura *, Eugenio Quaini {dagger}, and Piero Anversa * {ddagger}

*Department of Medicine, New York Medical College, Valhalla, NY 10595; and {dagger}Cardiac Surgery, Casa di Cura Poliambulanza, 25124 Brescia, Italy

Edited by Eugene Braunwald, Partners HealthCare System, Inc., Boston, MA, and approved July 8, 2003 (received for review May 12, 2003)

It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes.

This paper was submitted directly (Track II) to the PNAS office.

{ddagger} To whom correspondence should be addressed at: Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY 10595. E-mail: piero_anversa{at}nymc.edu.


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