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Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche

Nature Clinical Practice Cardiovascular Medicine volume 4, pages S21–S26 (2007)Cite this article

Abstract

Clinical and basic studies of cell-based myocardial therapy have proceeded at a rapid pace. Cell therapy could lead to successful cardiac regeneration or repair by any of three general mechanisms: differentiation of the administered cells into all of the cellular constituents of the heart; release of factors capable of paracrine signaling from the administered cells; and fusion of the administered cells with the existing constituents of the heart. Here, we argue that a fourth general mechanism could be operative: stimulation of endogenous repair by injected cells, which and might cause the regeneration of stem cell niches. In a porcine model of myocardial infarction, allogeneic mesenchymal stem cells stimulated substantial improvement in the ejection fraction, reduction of infarct size, and the growth of a rim of new cardiac tissue in the region in which the mesenchymal stem cells were injected. These effects occurred in the absence of definitive cardiac myocyte differentiation. After myocardial infarction, porcine hearts exhibit evidence of cardiac myocytes that have entered the cell cycle, neovascularization, and reduced levels of apoptosis. These data, in addition to new insights regarding the presence of endogenous cardiac stem cells, strongly support the concept that the heart could contain stem cell niches. Effective cell therapy could lead to restoration of these niches through multifaceted cell–cell interactions.

Key Points

  • Several mechanisms could explain the efficacy of cell-based therapies to repair cardiac injury

  • The mechanisms include cell differentiation and engraftment, and release of paracrine factors

  • Bone-marrow-derived mesenchymal stem cells stimulate myocardial recovery following injury, but evidence for differentiation is lacking

  • The heart contains endogenous stem cells that can be extracted and cultured ex vivo

  • The heart probably contains stem cell niches, which might represent structural and functional units mediating cardiac repair

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Figure 1: Loss of retention of allogeneic mesenchymal stem cells
Figure 2: Evidence of cardiac repair after myocardial infarction in the porcine heart
Figure 3: Evidence of cell division occurring after injection of mesenchymal stem cells into the infarcted tissue

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Acknowledgements

This work was supported by grants from the Johns Hopkins Specialized Center for Cell-Based Therapy, the Johns Hopkins University School of Medicine Institute for Cell Engineering (ICE), and the Donald W Reynolds Foundation and National Institutes for Health (NIH).

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Authors and Affiliations

  1. R Mazhari is a clinical fellow in the Division of Interventional Cardiology, and JM Hare is Professor of Medicine and Biomedical Engineering in the Department of Medicine/Division of Cardiology and the Specialized Center for Cell-Based Therapy, and Director of the Cardiovascular Section at the Institute for Cell Engineering (ICE), Johns Hopkins University School of Medicine, Baltimore, MD, USA.,

    Ramesh Mazhari & Joshua M Hare

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Correspondence to Joshua M Hare.

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Competing interests

Joshua M Hare has received research grants from Osiris Therapeutics Inc. R Mazhari declared she has no competing interests.

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Mazhari, R., Hare, J. Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat Rev Cardiol 4 (Suppl 1), S21–S26 (2007). https://doi.org/10.1038/ncpcardio0770

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