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Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny

Abstract

Stem cells have emerged as a next-generation therapy for cardiovascular disease. Initial clinical trials in patients with myocardial infarction document improved cardiac performance after administration of stem cells, translating their regenerative potential from the bench to the bedside. However, the promise of stem cell-based therapy has yet to be fully exploited, in part due to varying degrees of efficacy on follow-up. Contributing to the uncertain outcome is the variable cardiogenic potential of patient-derived stem cells. A strategy mimicking cardiogenic signaling was here formulated to transform mesenchymal stem cells, derived from human bone marrow, into cardiac progenitors. We identified a set of recombinant trophic factors capable of collectively inducing nuclear translocation of cardiac-specific transcription factors, engaging mesenchymal stem cells into cardiopoiesis, and ultimately securing a phenotype with functional excitation–contraction coupling. Maximizing the cardiogenic potential of human mesenchymal stem cells achieves a critical step in optimizing therapeutic translation.

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Figure 1: Cardiogenic potential of stem cells
Figure 2: Derivation of a cardiopoietic population from human mesenchymal stem cells yields functional progeny

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Acknowledgements

We thank DL Mann and C Mummery for the generous gifts of TNF-α-transgenic mice and endodermal cells, RS Faustino and RB Dyer for expert assistance, and S Vuk-Pavlovic for guidance and discussion. This work was supported by the National Institutes of Health, the Marriott Heart Disease Research Program, the Marriott Foundation, the Ted Nash Long Life Foundation, the Ralph Wilson Medical Research Foundation, and the Miami Heart Research Institute.

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Correspondence to Andre Terzic.

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Behfar, A., Terzic, A. Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny. Nat Rev Cardiol 3, S78–S82 (2006). https://doi.org/10.1038/ncpcardio0429

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  • DOI: https://doi.org/10.1038/ncpcardio0429

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