Cardiac Analysis of Autologous Transplantation of Cocultured Skeletal Myoblasts and Mesenchymal Cells in a Rat Model Doxorubicin-Induced Cardiotoxicity: Histopathological and Functional Studies

Abstract

Objective: Investigate the functional and histopathological effects of combined transplantation of mesenchymal stem cells (MSCs) and skeletal myoblasts (SM) in rats submitted to doxorubicin (DOX) induced cardiomyopathy. Methods:Myocardiopathy was induced through intraperitoneal applications of 3.75 mg/kg/day DOX once a week for 4 weeks in all experimental animals. Echocardiography examination was conducted to evaluate heart function. Myocardial cell apoptosis was examined morphologically by optical microscopy. The expression of both, von Willebrand factor and MyoD proteins was analysed using immunohistochemical staining. Results:Our results showed that all the experimental animals developed cardio-toxicity and exhibited decrease in heart function 4 weeks after the administration of DOX (P<0.05). The ventricular function significantly improved in rats that received sub-epicardial injection of co-culture of SM and MSC (CO group) when compared to rats that received only saline sub-epicardial injection (CG group) (P<0.05). Conclusion:The results of this study provide evidences that the myocardial co-culture transplantation of SM and MSCs contributed to the treatment the DOX-induced cardiotoxicity.

Mesenchymal Stem Cell Therapy for Doxorubicin-Induced Cardiomyopathy: Potential Mechanisms, Governing Factors, and Implications of the Heart Stem Cell Debate

“…The bone marrow, adipose tissue, and umbilical cord blood are the most common sites for MSC extraction. The most commonly used cells in the reviewed studies were BMMSCs (Chen et al, 2006; Garbade et al, 2009; Mohammadi Gorji et al, 2012; Yu et al, 2014; Ammar et al, 2015; Dias et al, 2015; Deng et al, 2017; Soliman et al, 2017; Zeng et al, 2017) and human umbilical cord blood (hUCB)-MSCs (Gopinath et al, 2010; Di et al, 2012; Abd Allah and Hussein, 2017; Mao et al, 2017; Mousa et al, 2018). Fewer studies used adipose-derived stem cells (ADSCs) (Oliveira et al, 2013; Pınarlı et al, 2013) and fetal-derived stem cells (Haydardedeoglu et al, 2018).…”