BACKGROUND: Cardiomyocyte apoptosis takes place at an early stage after myocardial infarction (MI). Therapy with mesenchymal stem cells (MSCs) is reported to reduce apoptosis. OBJECTIVES: To determine whether anoxic preconditioning (AP) could enhance the antiapoptotic effect of MSCs. METHODS: Cultured cardiomyocytes were treated with Dulbecco's modified Eagle's medium (as a control), MSCs or AP-MSCs, and were exposed to hypoxia/reoxygenation. Apoptotic cardiomyocytes were stained with Annexin V fluorescein isothiocyanate (BioVision, USA), visualized by fluorescence microscopy and analyzed by flow cytometry. In vivo, MI was produced in Sprague-Dawley rats by permanent ligation of the left anterior descending coronary artery and the left ventricles were randomly injected with Dulbecco's modified Eagle's medium, MSCs or AP-MSCs one week after MI. The cardiomyocyte apoptotic rate in peri-infarcted areas was assessed by terminal deoxynucleotidyltransferase- mediated 2'-deoxyuridine 5'-triphosphate nick end labelling assay one week after transplantation. Cardiac function was assessed by echocardiography four weeks after transplantation. Infarct size was measured by hematoxylin and eosin staining one and four weeks after transplantation. The expression of Bcl-2, Bax protein and cleaved cysteine-aspartic acid protease-3 was ana-lyzed by Western blot techniques. RESULTS: Cardiomyocyte apoptosis (both induced by hypoxia/ reoxygenation and MI) was significantly reduced by treating with MSCs and AP-MSCs, the Bcl-2 to Bax protein ratio was increased and cleaved cysteine-aspartic acid protease-3 was decreased. AP-MSCs were superior to MSCs. CONCLUSIONS: MSCs protected the infarcted heart by preventing cardio-myocyte apoptosis and AP enhanced the cardioprotective effects of MSCs.
BACKGROUND: Cardiomyocyte apoptosis takes place at an early stage after myocardial infarction (MI). Therapy with mesenchymal stem cells (MSCs) is reported to reduce apoptosis. OBJECTIVES: To determine whether anoxic preconditioning (AP) could enhance the antiapoptotic effect of MSCs. METHODS: Cultured cardiomyocytes were treated with Dulbecco's modified Eagle's medium (as a control), MSCs or AP-MSCs, and were exposed to hypoxia/reoxygenation. Apoptotic cardiomyocytes were stained with Annexin Vfluorescein isothiocyanate (BioVision, USA), visualized by fluorescence microscopy and analyzed by flow cytometry. In vivo, MI was produced in Sprague-Dawley rats by permanent ligation of the left anterior descending coronary artery and the left ventricles were randomly injected with Dulbecco's modified Eagle's medium, MSCs or AP-MSCs one week after MI. The cardiomyocyte apoptotic rate in peri-infarcted areas was assessed by terminal deoxynucleotidyltransferase- mediated 2'-deoxyuridine 5'-triphosphate nick end labelling assay one week after transplantation. Cardiac function was assessed by echocardiography four weeks after transplantation. Infarct size was measured by hematoxylin and eosin staining one and four weeks after transplantation. The expression of Bcl-2, Bax protein and cleaved cysteine-aspartic acid protease-3 was ana-lyzed by Western blot techniques. RESULTS: Cardiomyocyte apoptosis (both induced by hypoxia/ reoxygenation and MI) was significantly reduced by treating with MSCs and AP-MSCs, the Bcl-2 to Bax protein ratio was increased and cleaved cysteine-aspartic acid protease-3 was decreased. AP-MSCs were superior to MSCs. CONCLUSIONS: MSCs protected the infarcted heart by preventing cardio-myocyte apoptosis and AP enhanced the cardioprotective effects of MSCs.
Authors: Gerd P Meyer; Kai C Wollert; Joachim Lotz; Jan Steffens; Peter Lippolt; Stephanie Fichtner; Hartmut Hecker; Arnd Schaefer; Lubomir Arseniev; Bernd Hertenstein; Arnold Ganser; Helmut Drexler Journal: Circulation Date: 2006-03-06 Impact factor: 29.690
Authors: Massimiliano Gnecchi; Huamei He; Nicolas Noiseux; Olin D Liang; Lunan Zhang; Fulvio Morello; Hui Mu; Luis G Melo; Richard E Pratt; Joanne S Ingwall; Victor J Dzau Journal: FASEB J Date: 2006-04 Impact factor: 5.191
Authors: Jay G Shake; Peter J Gruber; William A Baumgartner; Guylaine Senechal; Jennifer Meyers; J Mark Redmond; Mark F Pittenger; Bradley J Martin Journal: Ann Thorac Surg Date: 2002-06 Impact factor: 4.330
Authors: Shinji Tomita; Donald A G Mickle; Richard D Weisel; Zhi-Qiang Jia; Laura C Tumiati; Yasmin Allidina; Peter Liu; Ren-Ke Li Journal: J Thorac Cardiovasc Surg Date: 2002-06 Impact factor: 5.209