Cardioprotective effects of fetal kidney-derived mesenchymal stem cells on doxorubicin-induced cardiotoxicity in rats

Abstract

Cardiotoxicity is one of the most common side effects of doxorubicin (DOX), a chemotherapy drug used in the treatment of many carcinomas. In recent years, stem-cell therapies have been successfully used to prevent cardiotoxicity. This study investigated the efficacy of intraperitoneally administered fetal kidney-derived mesenchymal stem cells (FKD-MSCs) in preventing DOX-induced cardiotoxicity in rats. For this purpose, thirty rats were randomly divided into three groups: control, DOX and mesenchymal stem cell (MSC) groups. Adriamycin was injected as a single dose via the tail vein in the DOX and MSC groups in order to induce cardiotoxicity. FKD-MSC was applied to the MSC group by the intraperitoneal route after cardiotoxicity had been established. Then the rats were euthanized, and routine histological procedures were performed on their hearts. H&E and Masson’s stains were used for histopathology. Cardiac Troponin-T and I (cTnT, cTnI), Caspase-3 and BCL-XL antibodies were used for immunohistochemistry. Vacuoles, edema, degeneration and necrosis were observed histopathologically mostly in the DOX group. Lesions in the control and MSC groups were less severe. Fibrosis in the control and MSC groups was milder. cTnT and cTnI immunopositive staining was most commonly seen in the control group, followed by the MSC group. Immunohistochemical staining by Caspase-3 and BCL-XL showed that their expressions in the MSC group were statistically similar to those in the control group. Accordingly, it was concluded that the intraperitoneal application of MSC had a positive effect on histopathological findings, fibrosis, immunohistochemistry, especially apoptosis, neovascularization, and anti-apoptotic development, whereas troponin levels were not found to be therapeutic.