Editors' ChoiceRegenerative Cardiology

Building Hearts, One Cell at a Time

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Science Translational Medicine  08 Jun 2011:
Vol. 3, Issue 86, pp. 86ec84
DOI: 10.1126/scitranslmed.3002718

Long before the discovery of stem cells, singer Linda Ronstadt crooned that “the heart is just like a wheel/When you bend it, you can't mend it.” She was wrong. The human heart is a dynamic ever-changing organ that increases in size and function with aerobic conditioning or pregnancy and can remodel itself after a myocardial infarction or in response to longstanding hypertension. Understanding the mechanisms that underlie human heart growth and development may hold the key to mending broken hearts through tissue regeneration. Now, Tulloch et al. study the developmental changes in immature human cardiomyocyte cells that were subjected to in vitro treatments designed to mimic certain conditions experienced by developing heart in vivo.

The authors evaluated the response of immature human myocardium to mechanical stress manipulation and vascularization using tissue engineering methods that provided the cells with a physiological three-dimensional environment. Using a collagen matrix embedded with human embryonic stem cell–derived cardiomyocytes, the researchers applied various forms of mechanical stress and assessed cardiomyocyte proliferation, maturation, and architecture. The cell-laden matrix constructs were stressed by using both static and cyclical methods and display increases in cell alignment, organization, DNA synthesis, and size (hypertrophy) as compared with that of constructs subjected to unstressed conditions. A vascular cell network was then added to the constructs. First, endothelial cells were added, which increased cardiomyocyte proliferation and the development of micro blood vessels (cord structures and lumens). The addition of support cells—specifically, mouse embryonic fibroblasts or human bone marrow stromal cells—gave rise to a marked increase in the presences of vessel cord structures and lumens. The engineered myocardial tissue was then grafted onto the epicardial surface of rat hearts. After 1 week, harvested hearts revealed that the grafts formed blood vessels that were perfused by the host circulation.

The authors conclude that engineered human myocardium that is exposed to both mechanical load and vascular-cell coculture controls cardiomyocyte proliferation and can be incorporated into cardiac tissue in vivo. These findings suggest that simulating physiological conditions in vitro is a necessary step in the regeneration of human myocardial tissue. These exciting results take scientists one step closer step to devising ways to repair injured hearts.

N. L. Tulloch et al., Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ. Res. 19 May 2011 (10.1161/CIRCRESAHA.110.237206). [Abstract]

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