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J Am Coll Cardiol, 2006; 47:1769-1776, doi:10.1016/j.jacc.2006.02.003 (Published online 11 April 2006).
© 2006 by the American College of Cardiology Foundation
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Cardiac Regeneration

Piero Anversa, MD*, Annarosa Leri, MD and Jan Kajstura, PhD

Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, New York.


Figure 1
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  		Figure 1 Myocyte proliferation in humans. A small dividing myocyte (alpha-sarcomeric actin, red) with metaphase chromosomes (arrow) is present in the left ventricular myocardium of a patient affected by chronic ischemic cardiomyopathy. Nuclei and metaphase chromosomes are labeled by propidium iodide (blue). Laminin defines the boundary of the cells (green).

 

Figure 2
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  		Figure 2 Chimerism of the transplanted female human heart. The localization of the Y-chromosome in the nucleus of a myocyte (A; alpha-sarcomeric actin, red; arrow), endothelial cell (B, arrow), and smooth muscle cells (B; {alpha}-smooth muscle actin, red; arrowheads) is illustrated in the left ventricle of a female heart transplanted in a male recipient. Laminin defines the boundary of the cells (A, green). A red blood cell is present in the lumen of the coronary arteriole (B; glycophorin; A, yellow).

 

Figure 3
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  		Figure 3 Bone marrow cells promote myocardial regeneration after infarction. The intramyocardial injection of enhanced green fluorescent protein (EGFP)-positive blood marrow cells in mice acutely after infarction induced the formation of new myocardium. In the infarcted region, the newly formed myocytes are small (A; alpha-sarcomeric actin, red) and show EGFP in the cytoplasm (B, green). (C) This merged image of A and B. The regenerated myocytes express both {alpha}-sarcomeric actin and EGFP (yellow-green). These myocytes are ~400 µm3 in volume and, because of their size, cannot be the product of cell fusion. Nuclei are labeled by propidium iodide (blue). *Spared myocytes in the subendocardium. EP = epicardium; EN = endocardium.

 

Figure 4
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  		Figure 4 Myocyte regeneration by bone marrow cells does not involve cell fusion. The intramyocardial injection of enhanced green fluorescent protein (EGFP)-positive male blood marrow cells in female mice acutely after coronary artery ligation induced the formation of male myocytes in the infarcted region. The newly formed myocytes are small (A; alpha-sarcomeric actin, red) and express EGFP in the cytoplasm (B, green). A small developing arteriole is also present (A; alpha-smooth muscle actin, yellow). The nuclei (C; propidium iodide, blue) contain at most one Y-chromosome (white dots) and one X-chromosome (magenta dots), indicating the male phenotype of these cells and therefore excluding cell fusion. (D) The merged images of A, B, and C. The regenerated myocytes express alpha-sarcomeric actin, EGFP (yellow-green), and one X- and one Y-chromosome.

 

Figure 5
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  		Figure 5 Cardiac stem cells (CSCs) and myocardial regeneration after infarction. The intramyocardial injection of enhanced green fluorescent protein (EGFP)-positive CSCs in syngeneic rats acutely after infarction induced the formation of myocardium. The new myocytes express alpha-sarcomeric actin (A, red) and EGFP in the cytoplasm (B, green). (C) The merged images of A and B. The regenerated myocytes show both {alpha}-sarcomeric actin and EGFP (yellow-green). Nuclei are labeled by propidium iodide (blue). (D) The formed myocytes are small and carry at most two chromosomes 12 (green dots). Therefore, myocyte regeneration does not involve cell fusion. Laminin is distributed between myocytes (white lines). (E, F) Regenerated coronary arterioles that are positive for alpha-smooth muscle actin and EGFP (yellow-red). *Spared myocytes in the subendocardium. EP = epicardium; EN = endocardium.

 




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