HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tang, J. Articles by Wang, M. Search for Related Content PubMed PubMed Citation Articles by Tang, J. Articles by Wang, M. Related Collections Cardiac - physiology Congestive Heart Failure Myocardial infarction

Eur J Cardiothorac Surg 2006;30:353-361
© 2006 Elsevier Science NL

Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion

^a Department of Physiology, XiangYa School of Medicine, Central South University, Changsha, Hunan 410078, People's Republic of China
^b Institute Of Clinical Medicine, Renmin Hospital, YunYang Medical College, Shiyan, Hubei 442000, People's Republic of China
^c Department of Physiology, YunYang Medical College, Shiyan, Hubei 442000, People's Republic of China
^d Stem Cells Research Institute of Hainan Province, Haikou 570102, Hainan, People's Republic of China

Received 6 October 2005; received in revised form 11 February 2006; accepted 20 February 2006.

^_* Corresponding author. Address: Department of Physiology, XiangYa School of Medicine, Central South University, Changsha, Hunan 410078, People's Republic of China. Tel.: +86 731 8905361; fax: +86 731 8905361. (Email: tangjm416{at}163.com; qxie18{at}hotmail.com; qxie{at}xysm.net; panther75{at}163.com; rywjn{at}vip.163.com; slwangmingjiang{at}sina.com).

Objective: The effect of transplanted mesenchymal stem cells (MSCs) on the left ventricular (LV) function and morphology in a rat myocardial infarct heart with reperfusion model were analyzed. Methods: One week after 60 min of myocardial ischemia and reperfusion by left anterior descending artery (LAD) occlusion, 1.0 x 10⁷ 6-diamidino-2-phenylindole (DAPI)-labeled MSCs were injected into the infarcted myocardium and compared with controls, and sham-operated rats, in which a cell-free serum medium was injected into the infarcted region or the myocardial wall, respectively. Measurement of vascular endothelial growth factor (VEGF) expression 1 week after MSC injection using Western blot analysis (n = 5), and immunohistochemical staining using HE staining and fluorescent microscopy of the DAPI-positive regions from MSC implantation, cTnT immunostaining of potential myocardial-like cells, and SM-actin and CD31 immunostaining demonstrating neovascular transformation of implanted MSCs 1 week, 2 weeks and 4 weeks after transplantation (n = 5). Hemodynamic measurements were performed after 4 weeks in vivo. Subsequently, hearts were quickly removed and cut for histological analysis using HE staining with measurement of the infracted LV-area, the LV-wall thickness within the scar segment compared to non-infarcted scar segments, and the capillary density counting capillary vessels with 400x light microscopy (n = 10). Results: Measurement of hemodynamics 4 weeks after transplantation in vivo showed LV function to be significantly greater in MSCs than in the control group. Semi-quantitative histomorphometric examinations showed a significantly lower infract size, a greater LV-wall thickness, and a lower Hochman-Choo expansion index in the MSC-treated group compared to the control group. Immunofluorescence demonstrated that transplanted MSCs were positive for cTnT, suggesting that a small number of transplanted MSCs can differentiate into cardiomyocytes. Other MSCs were positive for CD31 and SM-actin. The transplanted MSCs in MI area had significantly higher expression rates of cTnT, CD31 and SM-actin 2 weeks after transplantation. HE staining showed marked augmentation of neovascularization in the MSC group. Semi-quantitative analysis demonstrated that capillary density was significantly higher in the MSC group than in the control group. Conclusion: Implanted MSCs could improve cardiac structure and function through the combined effect of myogenesis and angiogenesis.

Key Words: Myocardial infarction • Mesenchymal stem cell • Angiogenesis • Transplantation • Rats

This article has been cited by other articles:

				J. Tang, J. Wang, J. Yang, X. Kong, F. Zheng, L. Guo, L. Zhang, and Y. Huang Mesenchymal stem cells over-expressing SDF-1 promote angiogenesis and improve heart function in experimental myocardial infarction in rats Eur. J. Cardiothorac. Surg., October 1, 2009; 36(4): 644 - 650. [Abstract] [Full Text] [PDF]

				S. Belmadani, K. Matrougui, C. Kolz, Y. F. Pung, D. Palen, D. J. Prockop, and W. M. Chilian Amplification of Coronary Arteriogenic Capacity of Multipotent Stromal Cells by Epidermal Growth Factor Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 802 - 808. [Abstract] [Full Text] [PDF]

				S. M. Chacko, M. Khan, M. L. Kuppusamy, R. P. Pandian, S. Varadharaj, K. Selvendiran, A. Bratasz, B. K. Rivera, and P. Kuppusamy Myocardial oxygenation and functional recovery in infarct rat hearts transplanted with mesenchymal stem cells Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1263 - H1273. [Abstract] [Full Text] [PDF]

				D. C. Vela, G. V. Silva, J. A.R. Assad, A. L.S. Sousa, S. Coulter, M. R. Fernandes, E. C. Perin, J. T. Willerson, and L. M. Buja Histopathological Study of Healing After Allogenic Mesenchymal Stem Cell Delivery in Myocardial Infarction in Dogs J. Histochem. Cytochem., February 1, 2009; 57(2): 167 - 176. [Abstract] [Full Text] [PDF]

				B. Zeng, H. Chen, C. Zhu, X. Ren, G. Lin, and F. Cao Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance Eur. J. Cardiothorac. Surg., October 1, 2008; 34(4): 850 - 856. [Abstract] [Full Text] [PDF]

				S. M. Hashemi, S. Ghods, F. D. Kolodgie, K. Parcham-Azad, M. Keane, D. Hamamdzic, R. Young, M. K. Rippy, R. Virmani, H. Litt, et al. A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction Eur. Heart J., January 2, 2008; 29(2): 251 - 259. [Abstract] [Full Text] [PDF]

				R. W. Grauss, E. M. Winter, J. van Tuyn, D. A. Pijnappels, R. V. Steijn, B. Hogers, R. J. van der Geest, A. A. F. de Vries, P. Steendijk, A. van der Laarse, et al. Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2438 - H2447. [Abstract] [Full Text] [PDF]