Effects of transplantation of bone marrow mesenchymal stem cells on hepatic injury and metabolism in rats with acute liver failure

This study was conducted to investigate the effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) on liver injury repair and metabolism in rats with acute hepatic failure for better clinical treatment of the disease. D-galactosamine (D-gal) and lipopolysaccharide (LPS) were used to construct rat models of acute liver failure (ALF). HE staining was used to examine the pathological changes of liver, liver function, and hepatic injury. Western blot was used to assay the expression of acute liver injury marker-betaine homocysteine S-methyltransferase (BHMT). BMSCs were isolated using the Percoll method and cultured in vitro for transplantation. SD rats were randomly divided into control, model and BMSC transplantation groups. For BMSC transplantation, the models were transplanted BMSC (10(7) cells/kg) at the third passage by tail vein injection while the rats in the model group received intraperitoneal injection of normal saline. Apoptosis of liver cells was determined using the TUNEL method and analyzed for the correlation with BMSC transplantation using Pearson correlation at different time points. Blood and liver tissue samples were analyzed for the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and lactate dehydrogenase (LDH), liver function, total protein (TP), cholesterol (CHO), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), and liver metabolites. The expression of IL-18 and its activating enzyme caspase-1 was using qRT-PCR. Based on tissue examination and BHMT level, it was confirmed that the ALF animal modeling was successful following D-Gal and LPS administration with a success rate of about 86.2%. 48 h after BMSC transplantation, the numbers of apoptosis-positive cells in control, model, and BMSC transplantation groups were 25.2 +/- 5.4, 58.6 +/- 8.4 and 32.1 +/- 2.2, respectively. Compared with the control group, the number was significantly upregulated (P < 0.05) in the models, while transplantation of BMSC reduced the number. Compared with the control group, serum levels of ALT, AST, TBIL, LDH, TG and LDL were significantly (P < 0.05) up-regulated in the model group, while TP level was reduced (P < 0.05). The mRNA level of IL-18 and Caspase-1 were significantly higher (P < 0.01) in the model than in the control group. Again, 48 h after BMSC transplantation, IL-18 and Caspase-1 expression were reduced to a certain extent. D-Gal combined with LPS is easy and effective to construct ALF rat model. BMSC transplantation can reduce apoptosis in liver tissue, restore metabolism and blood biochemical indicators. It also down-regulates the expression of IL-18 and caspase-1 at mRNA level.