Histological and immunohistochemical Study on the possible therapeutic effect of mesenchymal stem cells on cisplatin-induced cortical renal injury in mice

Abstract

Background Cisplatin (CIS) is a widely used anticancer drug. Despite its efficacy in treating solid tumors, it has many side effects, including acute renal failure. Previous studies have demonstrated that mesenchymal stem cells) MSCs) have a role in promoting cellular proliferation and regeneration. Aim The aim of this study was to investigate the possible therapeutic effect of bone marrow-derived MSCs on CIS-induced cortical renal injury in adult male mice. Materials and methods Thirty-six adult male mice were divided into four groups: group I served as the control group; group II (the CIS group) received a single intraperitoneal injection of 10 mg/kg CIS, and then the animals were killed after 72 h; group III (the stem cell therapy group) received a single intraperitoneal injection of 10 mg/kg CIS, and then the animals were injected with 2·106 MSCs suspended in 0.5 ml PBS into the caudal vein 72 h after CIS injection and left for 4 weeks before being killed; group IV (the recovery group) received a single intraperitoneal injection of 10 mg/kg CIS and left for 4 weeks to check for spontaneous recovery. Histological (using H&E stain), histochemical [periodic acid–Schiff (PAS) reaction], and immunohistochemical (using Ki67 antibody) studies were performed. Morphometric measurement of the optical density of PAS reaction was carried out and the mean number of Ki67 immunoreactive cells was ascertained, followed by statistical analysis. Results The CIS-only treated group showed ruptured glomerular capillaries, cytoplasmic vacuolization of tubular cells, flattening and loss of the epithelial lining cells of cortical tubules, and severe interstitial hemorrhage. A significant decrease in the optical density of PAS reaction, with decrease in the mean number of Ki67 immunoexpression, was found. MSCs improved the histological changes with significant increase in the optical density of PAS reaction and the mean number of Ki67 immunoexpression. Conclusion A therapeutic effect of MSCs was detected in CIS-induced cortical renal damage. This was evidenced by reversing the glomerular and tubular pathological changes in adult mice.