P0093 : Effect of mesenchymal stem cell on hepatic fibrosis in thioacetamide-induced cirrhotic rat model

Background: Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis and no effective therapy except liver transplantation is currently available for decompensated cirrhosis. However, some practical limitations in liver transplantation lead us to a need for new therapeutic paradigm in this field. Recent reports have shown that the mesenchymal stem cells (MSCs) have the plasticity to differentiate into some kinds of tissue cells and improve organ function. Hence, we investigated the effect of direct inoculation of human bone marrow derived MSCs (BM-MSCs) in thioacetamide (TAA)-induced cirrhosis in a rat model. Methods: Adult Sprague-Dawley rats were allocated into three groups (each group, n = 15) as follows: G1, shame; G2, TAAcontrol; G3, TAA+BM-MSC. To induce cirrhosis, 200mg/kg TAA injection was done twice a week for 12weeks in G2 and G3. 2×106 cells of amplified human BM-MSCs were injected directly into the right liver lobe twice, at weeks 6 and 8 in G3. At 12 weeks, the effect of BM-MSCs on cirrhosis was analyzed histomorphologically using Laennec scores. α-Smooth muscle actin(α-SMA) expression by immunohistochemical staining, relative expression of collagen type 1, and transforming growth factor β (TGF-β) were also evaluated by real-time reverse transcriptase- polymerase chain reaction. Results: Laennec scores were 0, 5.4±0.7 and 3.7±1.06 in G1, G2 and G3, respectively. Histologically, BM-MSCs injected group (G3) showed significant suppression of hepatic fibrosis compared with TAA-control group (G2)(P<0.001). Expressions of α-SMA(%) were significantly lower in G3 than in G2 (3.08±1.26 vs. 7.00±4.12, P<0.05). Also, the relative expression of collagen type 1 and TGF-β1 in RT-PCR were 0.64±0.24, 2.06±0.51, 1.32±0.31 and 0.62±0.28, 5.89±3.05, 2.22±1.41 in G1, G2 and G3, respectively P<0.005). Conclusions: Our results showed that BM-MSCs could attenuate liver fibrosis in rats with TAA-induced cirrhosis, raising the possibility for clinical use of BM-MSCs in the treatment of cirrhosis.