Transplantation of bone marrow-derived hepatocyte stem cells transduced with adenovirus-mediated IL-10 gene reverses liver fibrosis in rats

Abstract

Bone marrow stem cells (BMSCs) transplantation alone may not be sufficient for treatment of liver fibrosis because of complicated histopathologic changes in the liver. Interleukin-10 (IL-10) is an anti-fibrosis cytokine. IL-10 gene transfer of beta2m(-)/Thy-1+ bone marrow-derived hepatocyte stem cells (BDHSCs) may be useful for treating liver fibrosis. To determine the effect of liver fibrosis in rats by transplanting BDHSCs transduced with adenovirus-mediated IL-10 gene (AdIL-10), rat BDHSCs were isolated by magnetic bead cell sorting, characterized for liver-associated phenotypes, transduced with AdIL-10, and transplanted into liver-fibrotic rats. We show that BDHSCs secreted high-level IL-10 and retained their albumin expression after AdIL-10 transfer in vitro. Intra-portal-infused BDHSCs were implanted into the liver 2 weeks after transplantation. Transplanting AdIL-10-transduced BDHSCs into liver-fibrotic rats downregulated inflammatory response, promoted liver regeneration, suppressed activation of hepatic stellate cells and improved liver histopathology and liver function. These findings demonstrated the potential utility of this novel combined strategy of IL-10 gene and BDHSCs for the treatment of liver fibrosis.