title: Outcome improvement of cellular cardiomyoplasty using triple therapy: mesenchymal stem cell+erythropoietin+vascular endothelial growth factor.
abstract: To improve cellular cardiomyoplasty efficacy after myocardial infarction (MI), we postulated that combining mesenchymal stem cells (MSCs) transplantation with anti-apoptotic and angiogenic effects of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) may provide better prognosis in an infarcted heart 48 rats, underwent left anterior descending artery ligation, were divided into eight groups and treated as follows: Group 1: MSC+EPO+VEGF, Group 2: MSC+EPO, Group 3: MSC+VEGF, Group 4: MSC, Group 5: EPO+VEGF, Group 6: EPO, Group 7: VEGF and Group 8: Control. After MI induction, EPO and VEGF were injected subcutaneously at the dose of 3000 U/kg and 3 µg/kg respectively. MSCs were transplanted one week after MI. In the fourteenth and sixteenth days after infarction, EPO was injected again. Echocardiography demonstrated that all treatments improved left ventricular function significantly (before vs. after treatment) but in control group ejection fraction deteriorated over the 2-months period. Percent of ejection fraction recovery in all treatment groups were significantly greater than control (P<0.05). Compared with the control group, all treatments attenuated cell death in peri-infarct areas significantly, except groups 6 and 7. Vascular density of all treatment groups were more than control group but this superiority was statistically significant only in group 1 (P<0.01). All of our treatments had beneficial effects to some extent but MSC transplantation combined with EPO and VEGF administration resulted in superior therapeutic outcome in enhancing cell survival and neovascularization.
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran-1417614411, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Tavakoli
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Vahid
authors.initials: V
authors.lastname: Khori
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.forename: Anita
authors.initials: A
authors.lastname: Sadeghpour
authors.forename: Amir
authors.initials: A
authors.lastname: Darbandi Azar
authors.forename: Majid
authors.initials: M
authors.lastname: Haghjoo
authors.forename: Asghar
authors.initials: A
authors.lastname: Zare
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nayebpour
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018421:Cardiomyoplasty; D018929:Cell Culture Techniques; D002469:Cell Separation; D003131:Combined Modality Therapy; D004562:Electrocardiography; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010641:Phenotype; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin
keywords: Erythropoietin; Heart failure; Mesenchymal stem cell; Myocardial infarction; Vascular endothelial growth factor