Transplantation of bone marrow-derived liver stem cells transfected with rat IL-10 gene for liver fibrosis in rats

Abstract

Objective To explore the curative effectiveness of transplantation of bone marrow-derived liver stem cells (BDLSCs) transfected with rat interleukin-10 (IL-10) gene in the treatment of liver fibrosis in rats. Methods β2m-/Thy-1+BDLSCs isolated from Wistar rats were transfected with adenovirus-mediated rat IL-10 gene Wistar rats were subcutaneously injected with CCl4 to induce liver fibrosis, and randomly divided into three groups as follows: (1) the model group, infused with 1 ml normal saline (NS); (2) the BDLSC group, infused with NS containing untreated β2m-/Thy-1+BDLSCs (2×105 cells); (3) the IL-10 group, infused with NS containing β2m-/Thy-1+ BDLSCs transfected with IL-10 gene (2×105 cells). Infusion was done via the portal vein. Rats subcutaneously injected with olive oil served as control (the normal group). The BDLCs labeled with diamidine phenylindole dihydrochloride (DAPI) in the liver were localized. Pathological changes and collagen area in liver tissues were observed. Liver function and blood blotting function were tested. Results β2m-/Thy-1+ BDLSCs labeled with DAPI were observed in liver tissues of rats. Significant pathological changes of liver tissues were observed in the model group. Compared with the model group, pathological changes were alleviated to some extent in the BDLSC group. The morphology of liver tissue in the IL-10 group was mostly close to that in the normal group. Collagen deposition of liver tissues was increased obviously in the model group. However, transplantations of untreated and IL-10-transfected BDLSCs both reduced collagen area. Compared with the BDLSC group, collagen deposition was significantly suppressed in the IL-10 group. Transplantation of IL-10-transfected BDLSCs suppressed obviously the levels of ALT, AST, ALP, TBIL, PT and APTT as compared with the model group (P<0. 05). The levels of ALT, TBIL, PT and APTT in the IL-10 group were significantly reduced to the normal levels as compared with those in the BDLSC group (P<0. 05).Conclusions Transplantation of BDLSCs transfected with rat IL-10 gene was effective in treating liver fibrosis in rats. This combined strategy of IL-10 gene and BDLSCs may represent a feasible, effective and safe therapy form for liver fibrosis. Key words: Liver cirrhosis; Myeloid progenitor cells; Interleukin- 10