Title: Comparative Histological Study on the Effect of Mesenchymal Stem Cell and Losartan on Cardiac Injury Induced by Doxorubicin in Male Albino rats.

Introduction: Cardiovascular disease is the leading cause of death worldwide. Mesenchymal stem cells (MSCs) could be a promising therapy for treating cardiomyopathy. Aim of Work: To compare the therapeutic effects of MSCs and losartan (LOS) on doxorubicin (DOX) induced cardiomyopathy. Material and Methods: Thirty-nine male albino rats were divided into group I as a control group, group II received DOX 5 mg/kg ip once, group III received DOX as in group II `after 3 weeks LOS was given 30 mg/kg daily by gastric tube for 3 weeks and group IV received DOX as in group and after 3 weeks rats injected by 1ml of Paul Karl Haron (PKH)26 labeled MSCs iv. Blood samples were collected for estimating the creatine kinase-myocardial band (CK-MB) value. Cardiac muscle sections from all groups were examined by fluorescence microscope. All sections were processed for histological study using Hx&E and Masson’s trichrome stains in addition to immunohistochemical staining for Cx43 and CD44.Morphometric and statistical studies were done.Results: Group II revealed fragmented muscle fibers and cytoplasmic vacuolation in addition to loss of transverse striation. These changes were confirmed by significant increase in the mean value of CK-MB and the mean area % of collagen fibers when compared to all other groups. In group III, regression of the previous changes was noticed and there was a significant decrease in the mean area % of collagen fibers when compared to group II. Group IV cardiomyocytes appeared healthy with normal arrangement and non-significant difference in mean area % of collagen fibers versus the control. Studying all groups immunohistochemically, revealed increase in positive reactions in LOS and SC groups when compared to DOX group with more increase in SC group than LOS group.Conclusion: Losartan improves cardiac injury with little effect on cardiac regeneration. MSCs have promising potential in cardiac regeneration.