Abstract
BackgroundCirrhosis 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.MethodsThe 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 β1 (TGF-β1), type 1 collagen (collagen-1), α-smooth muscle actin (α-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays.ResultsAccording 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-β1, collagen-1, and α-SMA expression in TAA-induced cirrhotic rats (P <0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-β1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation.ConclusionsBM-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-014-0198-6) contains supplementary material, which is available to authorized users.
Highlights
Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis
In the untreated cirrhotic group, the liver sections were strongly stained by hematoxylin and eosin (H&E) and Masson’s trichrome (MTC), showing definite cirrhosis with regenerating nodules and fibrous septae (Figure 3A), whereas the bone marrow (BM)-mesenchymal stem cells (MSCs) treated group showed mild fibrosis (Figure 3B)
Through histological H&E and MTC, and α-smooth muscle actin (α-SMA) staining, we showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) administration resulted in significant improvement of hepatic fibrosis compared to the untreated cirrhotic group
Summary
Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Several previous studies using animal models of liver diseases have demonstrated that bone marrow (BM) cell transplantation may accelerate the liver regeneration process, reduce hepatic fibrosis, and improve liver function and survival [12,13,14,15]. The prospects for stem cell transplantation as a therapy for hepatic disease, as determined by initial translational pilot studies testing the direct hepatic administration of BM-derived stem cells, have been encouraging and have suggested enhanced liver regeneration prior to partial hepatectomy and improved liver function in advanced chronic liver disease [16,17,18,19,20,21,22]. Previous studies have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSCs) might be involved in the regression of liver fibrosis [23,24]
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