The role of hydrogen sulfide in enhancing the effectiveness of mesenchymal stem cell therapy in experimental model of heart failure / Maha Abdelmonem Mohammed Ahmed ; Supervised Amira A. Shaheen , Laila A. Rashed , Nancy N. Shahin

Thesis (Ph.D.) - Cairo University -Faculty of Pharmacy - Department of Biochemistry

Stem cell therapy represents a promising therapeutic avenue for cardiac disorders including heart failure. Although stem cell transplantation showed encouraging preliminary results, the outcomes of clinical studies are still unsatisfactory. This study aimed to compare the outcomes of two therapeutic approaches, in vivo co-delivery of sodium hydrogen sulfide (NaHS) concomitantly with bone marrow-derived mesenchymal stem cells (BMSCs) transplantation and in vitro preconditioning of BMSCs with NaHS, for promoting stem cell therapy in rats with isoprenaline-induced heart failure. Heart failure was developed 4 weeks after subcutaneous injection of isoprenaline (170 mg/kg) for 4 consecutive days. The in vivo approach involved co-delivery of intraperitoneally administered NaHS concomitantly with BMSC transplantation for a period of 14 days. The in vitro approach involved preconditioning of BMSC with NaHS for 30 min before transplantation. Compared to treatment with BMSCs alone, in vitro preconditioning of BMSCs with NaHS improved left ventricular function as measured by echocardiography and electrocardiography and enhanced stem cell homing, proliferation and differentiation as manifested by higher cardiac expression of GATA-4 and myocyte enhancer factor 2. Moreover, measurement of cardiac transforming growth factor beta 1level and histopathological investigation revealed mitigated fibrosis and myocardial injury score. The in vivo approach enhanced stem cell homing and differentiation, alleviated fibrosis and augmented vascular endothelial growth factor (VEGF)andendothelial nitric oxide synthase (eNOS) expression compared with BMSC therapy alone

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