Tohoku J. Exp. Med., 2012, 226(1)

Transplantation of Mesenchymal Stem Cells Preconditioned with Hydrogen Sulfide Enhances Repair of Myocardial Infarction in Rats

XINXING XIE,1 AIJUN SUN,1,2 WENQING ZHU,1 ZHEYONG HUANG,1 XINYING HU,1 JIANGUO JIA,1 YUNZENG ZOU1,2 and JUNBO GE1,2

1Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
2Institute of Biomedical Science, Fudan University, Shanghai, P.R. China

Stem cell transplantation has become a promising therapeutic approach for the treatment of myocardial infarction (MI). However, the poor survival of the donor cells after transplantation has restricted its therapeutic efficacy. Hydrogen sulfide (H2S), one gaseous signaling molecule, has been applied to inhibit cell apoptosis and promote cell survival. In the present study, we therefore examined the effects of H2S on the survival of mesenchymal stem cells (MSCs). MSCs were isolated from the femur of male Sprague-Dawley rats (about 4 weeks old, 100 g). Preconditioning MSCs with 200 μmol/L NaHS (as the donor of H2S) for 30 min decreased the hypoxia-induced cell apoptosis in vitro. The mechanisms contributing to the beneficial effects of H2S on MSCs were associated with increased levels of phosphorylated Akt (pAkt), phosphorylated Erk1/2 (pErk1/2) and phosphorylated glycogen synthase kinase-3β (pGSK-3β) in MSCs. Subsequently, MSCs (1 × 106), MSCs preconditioned with H2S (1 × 106), or phosphate buffered saline (PBS) were injected into rat hearts immediately after MI (the ligation of the left anterior descending of coronary artery). Real-time PCR for the Sry gene, located on the Y chromosome, indicated that preconditioning with H2S improved the survival rate of the transplanted MSCs in infarcted myocardium 4 days after MI, compared with the untreated MSCs. Furthermore, transplantation of the H2S-pretreated MSCs reduced the infarct size and increased left ventricular (LV) function, as judged by transthoracic echocardiography. In conclusion, H2S preconditioning effectively promotes MSCs survival under ischemic injury and helps cardiac repair after MI, which has great clinical significance.

keywords —— cell survival; cell transplantation; hydrogen sulfide; mesenchymal stem cells; myocardial infarction

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 226, 29-36

Correspondence: Junbo Ge, M.D., FACC, FESC, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, P.R. China.

e-mail: junboge@126.com