Abstract
Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment.
Highlights
Epidemiological analysis has revealed an increase in deaths caused by liver cirrhosis from 676,000 to over 1 million in 2010 [1]
AST and ALT levels were decreased in bone marrow-derived mesenchymal stem cells (BM-mesenchymal stem cells (MSCs)) infusion groups (p < 0.05, compared with phosphatebuffered saline (PBS)-treated groups; Figures 2(a) and 2(b)). These results indicated that transplantation of Bone marrow (BM)-MSCs could prevent liver damage to a certain extent
The results indicated that BM-MSC transplantation ameliorated necroinflammatory and cirrhosis scores
Summary
Epidemiological analysis has revealed an increase in deaths caused by liver cirrhosis from 676,000 to over 1 million in 2010 [1]. Hepatic cirrhosis is characterized by accumulation of extracellular matrix (ECM) proteins [2, 4], loss of liver functions, and activation of hepatic stellate cells (HSCs) [5]. Orthotopic liver transplantation (OLT) is considered as the gold standard [6, 7], but there is an organ donor shortage and a large number of liver cirrhosis patients. The number of OLT procedures has decreased because of the lack of organ donors [2]. Cell transplantation is recommended as a potential approach for treatment of hepatic fibrosis. MSCs can be differentiated into a variety of cell types including hepatocytes [13,14,15,16,17,18]
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