Transplantation of bone marrow-derived mesenchymal stem cells after regional hepatic irradiation ameliorates thioacetamide-induced liver fibrosis in rats.

BACKGROUND

Recent studies have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSCs) can potentially revert liver fibrosis, but it is not known if preparative hepatic irradiation (HIR) contributes to the therapeutic effect of transplanted BM-MSCs. In this study, we investigate the effects of HIR on transplanted BM-MSCs in cirrhotic rats and the underlying mechanism by which mesenchymal stem cells (MSCs) relieve liver fibrosis.

MATERIALS AND

METHODS

The BM-MSCs from male rats were labeled with CM-Dil and injected via portal vein into two groups of thioacetamide-induced cirrhotic rats, and the controls were injected with the same volume of saline. The right hemiliver of one cirrhotic rat group was irradiated (15 Gy) 4 d before transplantation. Liver function tests and histologic experiments were performed, and the liver population of BM-MSCs was estimated.

RESULTS

The transplantation of MSCs alleviated liver fibrosis and reduced expression of transforming growth factor-β1, Smad2, collagen type I, and α-SMA. HIR preconditioning promoted homing and repopulation of MSCs and resulted in better treatment outcomes.

CONCLUSIONS

HIR preconditioning enhances the effect of BM-MSCs in improving thioacetamide-induced liver fibrosis in rats by promoting their homing and repopulation. BM-MSCs may function by inhibiting transforming growth factor-β1-Smad signaling pathway in the liver.