Inhibition of liver fibrosis by IL-10 gene-modified BMSCs in a rat model / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>IL-10 gene-modified BMSCs are effective for treating liver fibrosis in a CCl4-induced rat model.</p>