Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model

Background: Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Hence, we investigated the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model. Methods: The BM-MSCs were injected directly into the right liver lobe twice, at 6 and 8 weeks during the 12-week TAA administration, in thioacetamide (TAA)-induced cirrhotic rats model, and hepatic fibrosis was evaluated. At 12 weeks, the effect of BM-MSCs on hepatic fibrosis was analyzed histomorphologically using the Laennec fibrosis scoring system, and the collagen proportionate area was quantified. Cirrhosis-related factors, such as transforming growth factor beta 1 (TGF-beta 1), type 1 collagen (collagen-1), alpha-smooth muscle actin (alpha-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays. Results: According to the Laennec fibrosis scoring system, histological improvement was observed in hepatic fibrosis after BM-MSC treatment (P < 0.01). The percentage of the collagen proportionate area decreased from 16.72 +/- 5.51 to 5.06 +/- 1.27 after BM-MSC treatment (P < 0.01). The content of hepatic hydroxyproline was significantly lower in the BM-MSC treated group (46.25 +/- 13.19) compared to the untreated cirrhotic group (85.81 +/- 17.62; P < 0.01). BM-MSC administration significantly decreased TGF-beta 1, collagen-1, and alpha-SMA expression in TAA-induced cirrhotic rats (P < 0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-beta 1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation. Conclusions: BM-MSC treatment attenuated hepatic fibrosis in rats with TAA-induced cirrhosis, raising the possibility of the clinical use of BM-MSCs in the treatment of cirrhosis.