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Antiapoptotic Effect of Implanted Embryonic Stem Cell-Derived Early-Differentiated Cells in Aging Rats After Myocardial Infarction

¹ The 2^nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.
Divisions of ² Cardiology and ³ Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
⁴ Division of Cardiovascular Medicine, Department of Medicine, Caritas St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, Massachusetts.

Address correspondence to James P. Morgan, MD, PhD, Division of Cardiovascular Medicine, Department of Medicine, Caritas St. Elizabeth's Medical Center, 736 Cambridge Street, Boston, MA 02135. E-mail: james.morgan{at}caritaschristi.org or Jiang-Yong Min, MD, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: jmin{at}bidmc.harvard.edu

This study tested whether implanted embryonic stem cell-derived early-differentiated cells (EDCs) lead to improvement in cardiac function by preventing cardiac apoptosis in aging rats after myocardial infarction. Cardiac apoptosis after transplantation of EDCs was assessed in situ by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling reaction (TUNEL) staining as well as by measurements of protein levels of cleaved caspases 3, Bax, and Bcl-2. Our results indicate that cell transplantation improved cardiac function at 6-months observation. The frequency of apoptotic cells in the peri-infarcted myocardium 3 days after cell transplantation was significantly decreased in the cell transplantation group. EDC therapy decreased the protein levels of cleaved caspase 3 and Bax, and increased the level of Bcl-2 in comparison to myocardial infarction control. Additionally, the number of apoptotic cells decreased significantly in cardiomyocytes precocultured with EDCs. This study demonstrates that functional improvement of EDC transplantation may at least in part be related to a reduction in cardiomyocyte apoptosis.