Objective: The aim of this study was to assess and compare the therapeutic effects of allogenic and xenogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) on a rat model for treating experimental lung inflammation, oxidative stress, and apoptosis.
Materials and methods: Male Wistar rats were randomly divided into four groups. Group 1 received an intraperitoneal injection of olive oil vehicle (2 mL/kg body weight) for 8 weeks. Group 2 received an intraperitoneal injection of carbon tetrachloride (CCl4) (0.5 mL/kg body weight, twice/week) dissolved in olive oil for 8 weeks. Groups 3 and 4 received the CCl4 similar to group 2, followed by the intravenous injection of rat and mouse BM-MSCs (1 × 106 cells/rat twice/week into a lateral tail vein), respectively, for 4 weeks. Subsequently, the rats were sacrificed, and lung tissues were excised for molecular, histological, and ultrastructural investigations.
Results: Fibrosis, interstitial bleeding, dilatation and congestion of blood vessels, intra-alveolar edema, damaged alveoli, scattered mononuclear leucocytic infiltrates, and an increased number of apoptotic cells and apoptotic remnants were observed in the lungs of rats exposed to CCl4; the treatment with rat and mouse BM-MSCs attenuated these changes. The effects of CCl4 on the increase in collagen fibers in the lungs and the expression levels of cyclooxygenase-2, tumor necrosis factor-α, and apoptotic protein p53 were considerably reduced following treatment with the BM-MSCs. The higher levels of lipid peroxidation, the lower-level glutathione content, and the activities of superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase in CCl4-injected rats were significantly improved by treatments with rat and mouse BM-MSCs.
Conclusions: These findings indicate that mouse and rat BM-MSCs, which were more potent, can protect against CCl4-induced lung damage and fibrosis by reducing inflammation, apoptosis, and oxidative stress and boosting the antioxidant defense system.