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The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells

Nature Clinical Practice Cardiovascular Medicine volume 4, pages S27–S39 (2007)Cite this article

Abstract

Adequate cell-based repair of adult myocardium remains an elusive goal because most cells that are used cannot generate mature myocardium sufficient to promote large functional improvements. Embryonic stem cells can generate both mature cardiocytes and vasculature, but their use is hampered by associated teratoma formation and the need for an allogeneic source. The detection of sca-1+, c-kit+, or isl-1+ cardiac precursors and the creation of cardiospheres from adult heart tissues suggest that a persistent population of immature progenitor cells is present in the mature myocardium. These cell populations probably represent stages along a continuum of cardiac stem cell development and differentiation. We report isolation from ventricle of uncommitted cardiac progenitor cells, which appear to resemble the more immature, common pool of embryonic lateral plate mesoderm progenitors that yield both myocardial and endocardial cells during normal cardiac development. Under controlled in vitro conditions and in vivo, these cells can differentiate into endothelial, smooth muscle, and cardiomyocyte lineages and can be isolated and expanded to clinically relevant numbers from adult rat myocardial tissue. In this article, we discuss the potential for autologous repair or even cardiac regeneration with cells that follow a developmental pathway similar to embryonic cardiac precursors but without the inherent limitations associated with undifferentiated embryonic stem cells.

Key Points

  • Uncommitted cardiac-derived progenitor cells (UPCs) can be isolated from adult mammalian heart and expanded in vitro

  • UPCs resemble undifferentiated embryonic stem cells and recapitulate cardiac development when exposed to cardiac differentiation conditions in vitro

  • These cells may give rise to other cardiac stem cell populations

  • UPCs improve left ventricular function when transplanted after myocardial injury and differentiate into cardiomyocyte-like and vascular cells

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Figure 1: SSEA-1+ progenitor cells in rat postnatal myocardia
Figure 2: Characterization of adult heart-derived progenitor cells isolated from primary cultures
Figure 3: Schematic representations of in vitro recapitulation of cardiac development of and application of UPCs
Figure 4: Primary culture of ventricular mechanically and enzymatically processed rat ventricular myocardium
Figure 5: In vitro differentiation of adult heart-derived UPCs with cardiocyte coculture
Figure 6: Functional repair and myocardial regeneration after undifferentiated progenitor cell transplantation in a rat left anterior descending coronary artery ligation model
Figure 7: Left ventricular function and remodeling after treatment with UCPs, compared with control

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Authors and Affiliations

  1. J Brechtken is a Fellow in Cardiology in the Division of Cardiology, and DA Taylor is Medtronic Bakken Professor in the Department of Integrative Biology and Physiology, Department of Surgery, HC Ott formerly was Scientific Director, TS Matthiesen, S Grindle, and W Nelson are scientists, S-K Goh is an assistant scientist, and DA Taylor is Director in the Center for Cardiovascular Repair, University of Minnesota, MN, USA. HC Ott is currently a resident in general surgery, Massachusetts General Hospital, Boston, MA, USA.,

    Harald C Ott, Thomas S Matthiesen, Johannes Brechtken, Suzanne Grindle, Saik-Kia Goh, Wendy Nelson & Doris A Taylor

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  1. Harald C Ott
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Correspondence to Doris A Taylor.

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Ott, H., Matthiesen, T., Brechtken, J. et al. The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells. Nat Rev Cardiol 4 (Suppl 1), S27–S39 (2007). https://doi.org/10.1038/ncpcardio0771

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