Stem cell therapy in the aging hearts of Fisher 344 rats: Synergistic effects on myogenesis and angiogenesis Jiang-Yong Min, MD, Yu Chen, MD, Sohail.

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Stem cell therapy in the aging hearts of Fisher 344 rats: Synergistic effects on myogenesis and angiogenesis Jiang-Yong Min, MD, Yu Chen, MD, Sohail Malek, BS, Achim Meissner, MD, Meixiang Xiang, MD, PhD, Qinen Ke, MD, Xin Feng, MD, Masaharu Nakayama, MD, PhD, Emel Kaplan, MD, James P. Morgan, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 130, Issue 2, Pages 547-553 (August 2005) DOI: 10.1016/j.jtcvs.2005.03.017 Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Inotropic response of the LVSP to isoproterenol (ISO) stimulation during hemodynamic measurements in vivo. Original representative recordings (A) show the response to isoproterenol stimulation was blunted in the aging heart without cell treatment. ES cell transplantation partially restored the inotropic response to β-adrenergic stimulation 6 weeks after cell injection. Summarized data are shown in panel B. *P < .05 and **P < .01 versus adult group; #P < .05, aging + ES cell group versus aging group. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 547-553DOI: (10.1016/j.jtcvs.2005.03.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 The results of the left ventricular blood flow measurements with isotope microspheres are shown (A). ES cell transplantation significantly restored the regional blood flow compared with the aging heart without cell treatment. A linear regression study (B) demonstrated a weak association between the LVSP and the regional blood flow. *P < .05 and **P < .01 versus adult group; #P < .05, aging + ES cell group versus aging group. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 547-553DOI: (10.1016/j.jtcvs.2005.03.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Myocyte counts from the adult and the aging heart with or without cell transplantation (A). The aging heart without cell therapy showed significant loss of cardiac myocytes. ES cell transplantation partially restored the myocyte number toward normal values. A linear regression study (B) demonstrated a moderate association between the LVSP and the number of myocytes. LV, Left ventricle. *P < .05 and **P < .01 versus adult group; #P < .05, aging + ES cell group versus aging group. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 547-553DOI: (10.1016/j.jtcvs.2005.03.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Protein expressions of SERCA2 (5 for each group) in left ventricles from adult rats, aging rats, and aging rats with cell transplantation determined by means of the Western blot technique. A, Western blot; B, densitometric analysis of SERCA2/reduced glyceraldehyde-phosphate dehydrogenase (GAPDH). *P < .05 and **P < .01 versus adult group; #P < .05, aging + ES cell group versus aging group. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 547-553DOI: (10.1016/j.jtcvs.2005.03.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Panel A shows engrafted ES cells with hematoxylin and eosin staining in the aging myocardium 6 weeks after cell transplantation. Panel B shows the higher magnification image corresponding with the image in panelA pointed out by a dot-lined rectangle to show regenerated tissue from implanted ES cells. GFP-positive spots are shown within the aging host myocardium in panel C. The α-MHC staining of the myocardial section from the aging heart with cell transplantation, as shown in panel D, indicates the positive staining not only displayed in the host myocardium but also in the regenerated tissue. Panel E shows colocalization of transplanted ES cells by using fluorescent staining for cardiac α-MHC. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 547-553DOI: (10.1016/j.jtcvs.2005.03.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions