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Generation of Functional Ventricular Heart Muscle from Mouse Ventricular Progenitor Cells

Science  16 Oct 2009:
Vol. 326, Issue 5951, pp. 426-429
DOI: 10.1126/science.1177350

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A Fix to the Heart

Regenerative cardiovascular medicine is a promising avenue for therapeutic application in advanced heart failure. Although clinical trials have suggested some limited benefits in cell transplantation therapy, robust cardiac muscle formation is lacking. Domian et al. (p. 426) examined the developmental processes in normal mature cardiac muscle. A two-color murine reporter system was used to isolate committed ventricular progenitors, which were then used to build functional force-generating cardiac tissue. Such combinations of tissue engineering and stem cell biology may eventually lead to cardiac regenerative therapy.

Abstract

The mammalian heart is formed from distinct sets of first and second heart field (FHF and SHF, respectively) progenitors. Although multipotent progenitors have previously been shown to give rise to cardiomyocytes, smooth muscle, and endothelial cells, the mechanism governing the generation of large numbers of differentiated progeny remains poorly understood. We have employed a two-colored fluorescent reporter system to isolate FHF and SHF progenitors from developing mouse embryos and embryonic stem cells. Genome-wide profiling of coding and noncoding transcripts revealed distinct molecular signatures of these progenitor populations. We further identify a committed ventricular progenitor cell in the Islet 1 lineage that is capable of limited in vitro expansion, differentiation, and assembly into functional ventricular muscle tissue, representing a combination of tissue engineering and stem cell biology.

  • * These authors contributed equally to this work.

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