Inhibition of liver fibrosis by IL-10 gene-modified BMSCs in a rat model

Abstract

To investigate the potential curative effects of bone marrow mesenchymal stem cells (BMSCs) overexpressing IL-10 for treating liver fibrosis by using a CCl4-induced rat model. BMSCs were cultured and marked by DAPI staining of the cells' nuclei. Meanwhile, 60 Wistar rats were treated with CCl4 to induce liver fibrosis and randomly divided into three groups: A: injected with DAPI-marked BMSCs transfected with pcDNA3.0-IL-10; B: injected with DAPI-marked BMSCs; C: injected with phosphate-buffered saline. Histological analysis of excised livers was conducted to observe BMSCs (by DAPI marker) and fibrosis (by Masson's stain). Western blotting was used to detect IL-10 expression in BMSCs. Effects on expression of tumor necrosis factor-alpha (TNFa) were analyzed by enzyme-linked immunosorbent assay, and on hydroxyproline (HYP) levels were analyzed by the acid hydrolysis method. Following CCl4-inducement, rat livers showed the characteristic pathological changes of fibrosis and DAPI-marked cells (BMSCs) were observed. Compared with group C (pulmonary fibrosis score: 3.15+/-0.96; HYP level: 1.89+/-1.03 mug/mg), the extent of liver fibrosis was significantly lower in group A (pulmonary fibrosis score: 1.01+/-0.35; HYP level: 0.73+/-0.29 mug/mg) and group B (pulmonary fibrosis score: 1.34+/-0.65; HYP level: 1.21+/-0.78 mug/mg). The therapeutic effects were significantly greater in group A than group B (q=-4.73, P less than 0.05). TNFa protein expression was significantly lower in group A (275.21+/-86.35) and group B (321.76+/-98.49) than in group C (476.23+/-126.43). The TNFa expression was significantly lower in group A than group B (q=-7.43, P less than 0.05). IL-10 gene-modified BMSCs are effective for treating liver fibrosis in a CCl4-induced rat model.