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Eur J Cardiothorac Surg 2008;34:850-856. doi:10.1016/j.ejcts.2008.05.049
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
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Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance

Bin Zenga,*, Honglei Chenb, Chengang Zhuc, Xiaofeng Rend, Guosheng Lina,*, Feng Caoa

a Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, PR China
b Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei, PR China
c State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, PR China
d College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, PR China

Received 28 December 2007; received in revised form 13 May 2008; accepted 28 May 2008.

* Corresponding authors. Tel.: +11 86 27 88901944; fax: +11 86 27 88901944. (Email: zengbin19982005{at}yahoo.com.cn; lguosheng10272005{at}yahoo.com.cn).

Objective: Bone marrow mesenchymal stem cells (MSCs) have the potential to repair the infarcted myocardium and improve cardiac function. However, this approach is limited by its poor viability after transplantation, and controversy still exists over the mechanism by which MSCs contribute to the tissue repair. Methods: The human heme oxygenase-1 (hHO-1) was transfected into cultured MSCs using an adenoviral vector. 1 x 106 Ad-hHO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS only (PBS group) were injected intramyocardially into rat hearts 1 h after myocardial infarction. Results: HO-1-MSCs survived in the infarcted myocardium, and expressed hHO-1 mRNA. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was significantly enhanced in HO-1-MSCs-treated hearts. At the same time, there were significant reduction of TNF-{alpha}, IL-1-beta and IL-6 mRNA, and marked increase of IL-10 mRNA in HO-1-MSCs-treated hearts. Moreover, a further downregulation of proapoptotic protein, Bax, and a marked increase in microvessel density were observed in HO-1-MSCs-treated hearts. The infarct size and cardiac performance were also significantly improved in HO-1-MSCs-treated hearts. Conclusion: The combined approach improves MSCs survival and is superior to MSCs injection alone.

Key Words: Mesenchymal stem cells • Myocardial infarction • Heme oxygenase-1 • Paracrine factors • Angiogenesis






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Copyright © 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved.