title: Transplantation of mesenchymal stem cells preconditioned with hydrogen sulfide enhances repair of myocardial infarction in rats.
abstract: 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 (H(2)S), 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 H(2)S 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 H(2)S) for 30 min decreased the hypoxia-induced cell apoptosis in vitro.  The mechanisms contributing to the beneficial effects of H(2)S 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 × 10(6)), MSCs preconditioned with H(2)S (1 × 10(6)), 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 H(2)S improved the survival rate of the transplanted MSCs in infarcted myocardium 4 days after MI, compared with the untreated MSCs.  Furthermore, transplantation of the H(2)S-pretreated MSCs reduced the infarct size and increased left ventricular (LV) function, as judged by transthoracic echocardiography.  In conclusion, H(2)S preconditioning effectively promotes MSCs survival under ischemic injury and helps cardiac repair after MI, which has great clinical significance.
authors.affiliation: Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Xie
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Wenqing
authors.initials: W
authors.lastname: Zhu
authors.forename: Zheyong
authors.initials: Z
authors.lastname: Huang
authors.forename: Xinying
authors.initials: X
authors.lastname: Hu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Jia
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018929:Cell Culture Techniques / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D004452:Echocardiography; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009203:Myocardial Infarction / Q000628:therapy*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051876:Sex-Determining Region Y Protein / Q000378:metabolism
chemical_list: D017931:DNA Primers; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D038362:Glycogen Synthase Kinase 3; D006862:Hydrogen Sulfide