Regenerating new heart with stem cells
Piero Anversa, … , Marcello Rota, Annarosa Leri
Piero Anversa, … , Marcello Rota, Annarosa Leri
Published January 2, 2013
Citation Information: J Clin Invest. 2013;123(1):62-70. https://doi.org/10.1172/JCI63068.
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Regenerating new heart with stem cells

Abstract

This article discusses current understanding of myocardial biology, emphasizing the regeneration potential of the adult human heart and the mechanisms involved. In the last decade, a novel conceptual view has emerged. The heart is no longer considered a postmitotic organ, but is viewed as a self-renewing organ characterized by a resident stem cell compartment responsible for tissue homeostasis and cardiac repair following injury. Additionally, HSCs possess the ability to transdifferentiate and acquire the cardiomyocyte, vascular endothelial, and smooth muscle cell lineages. Both cardiac and hematopoietic stem cells may be used therapeutically in an attempt to reverse the devastating consequences of chronic heart failure of ischemic and nonischemic origin.

Authors

Piero Anversa, Jan Kajstura, Marcello Rota, Annarosa Leri

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Figure 4

Transdifferentiation of c-kit–positive HSCs.

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Transdifferentiation of c-kit–positive HSCs. (A) Schematic representatio...
(A) Schematic representation of transgene constructs used in the generation of donor mice for the acquisition of HSCs to be delivered after infarction. In each case, the promoter that controls the ubiquitous (β-actin) or myocyte-restricted (α-MHC) expression of the transgene (EGFP or c-myc–tagged nuclear-targeted Akt) is shown. c-kit–positive HSCs from donor males were injected intramyocardially in wild-type female infarcted mice. NLS, nuclear localization signal (ref. 75). (B) Infarcted female mouse treated with male HSCs. Regenerated myocytes (left; MHC, red) carry the Y chromosome (center; Y-chr; white dots in nuclei). Merged image is shown at right. Arrows indicate non-regenerated infarct. A thin layer of spared myocytes is present in the epimyocardium (EP) and endomyocardium (EN) (ref. 75). Scale bar: 50 μm. (C) Examples of myocytes isolated from the regenerated myocardium of mice injected with HSCs collected from β-actin EGFP, α-MHC EGFP, or α-MHC c-myc–tagged nuclear-targeted Akt mice. Top panels illustrate the localization of EGFP (left and middle, green; arrowheads) and c-myc (right, yellow nuclei; arrows) in newly formed cardiomyocytes. Bottom panels show the colocalization of α-SA and EGFP (yellow, arrowheads) and of α-SA and c-myc (yellow nuclei, arrows). Large spared myocytes negative for EGFP or c-myc are also present (ref. 75). Scale bar: 50 μm. (D) Myocyte-specific ionic currents and action potentials of a cell isolated from the regenerated infarcted myocardium. EGFP-positive myocytes show contractile activity (bottom). Original magnification, ×200. Reproduced with permission from Proceedings of the National Academy of Sciences of the United States of America (ref. 75; copyright 2007, National Academy of Sciences, USA).