Rezvan Esmaeili1, Amir Darbandi-Azar2, Anita Sadeghpour3, Keivan Majidzadeh-A4, Leila Eini5, Narges Jafarbeik-Iravani6, Parisa Hoseinpour7, Alireza Vajhi8, Tayebeh Oghabi Bakhshaiesh6, Farzad Masoudkabir9, Majid Sadeghizadeh10. 1. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran; Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran. 2. Rajaie Cardiovascular Medical and Research Centre, Iran University of Medical Sciences, Tehran, Iran. 3. Echocardiography Research Center, Department of Cardiovascular Medicine, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran. 4. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran; Tasnim Biotechnology Research Center (TBRC), Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran. Electronic address: kmajidzadeh@acecr.ac.ir. 5. Cell and Immunotherapy Department, Breast Cancer Research Center, Motamed Cancer Institute ACECR, Tehran, Iran. 6. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran. 7. Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran. 8. Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. 9. Cardiac Primary Prevention Research Center, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. 10. Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: sadeghma@modares.ac.ir.
Abstract
BACKGROUND: Stem cell therapy is among the novel approaches for the treatment of post-myocardial infarction cardiomyopathy. This study aims to compare the effect of stromal-derived factor 1 α (SDF1α), mesenchymal stem cells (MSCs) in combination with the lentiviral production of vascular endothelial growth factor (VEGF) on infarct area, vascularization and eventually cardiac function in a rat model of myocardial infarction (MI). METHODS: The influence of SDf1α on MSCs survival was investigated. MSCs were transduced via a lentiviral vector containing VEGF. After that, the effect of mesenchymal stem cell transfection of VEGF-A165 and SDf1α preconditioning on cardiac function and scar size was investigated in five groups of MI rat models. The MSC survival, cardiac function, scar size, angiogenesis, and lymphocyte count were assessed 72 hours and 6 weeks after cell transplantation. RESULTS: SDF1α decreased the lactate dehydrogenase release in MSCs significantly. Also, the number of viable cells in the SDF1α-pretreated group was meaningfully more than the control. The left ventricular systolic function significantly enhanced in groups with p240MSC, SDF1αMSC, and VEGF-A165MSC in comparison to the control group. CONCLUSIONS: These findings suggest that SDF1α pretreatment and overexpressing VEGF in MSCs could augment the MSCs' survival in the infarcted myocardium, reduce the scar size, and improve the cardiac systolic function.
BACKGROUND: Stem cell therapy is among the novel approaches for the treatment of post-myocardial infarction cardiomyopathy. This study aims to compare the effect of stromal-derived factor 1 α (SDF1α), mesenchymal stem cells (MSCs) in combination with the lentiviral production of vascular endothelial growth factor (VEGF) on infarct area, vascularization and eventually cardiac function in a rat model of myocardial infarction (MI). METHODS: The influence of SDf1α on MSCs survival was investigated. MSCs were transduced via a lentiviral vector containing VEGF. After that, the effect of mesenchymal stem cell transfection of VEGF-A165 and SDf1α preconditioning on cardiac function and scar size was investigated in five groups of MI rat models. The MSC survival, cardiac function, scar size, angiogenesis, and lymphocyte count were assessed 72 hours and 6 weeks after cell transplantation. RESULTS: SDF1α decreased the lactate dehydrogenase release in MSCs significantly. Also, the number of viable cells in the SDF1α-pretreated group was meaningfully more than the control. The left ventricular systolic function significantly enhanced in groups with p240MSC, SDF1αMSC, and VEGF-A165MSC in comparison to the control group. CONCLUSIONS: These findings suggest that SDF1α pretreatment and overexpressing VEGF in MSCs could augment the MSCs' survival in the infarcted myocardium, reduce the scar size, and improve the cardiac systolic function.