Pharmacological Mobilization Of Bone Marrow Stem Cells Ameliorates Liver Fibrosis In Rats With Carbon Tetrachloride Induced Injury

The liver is a vital organ of vertebrates and humans.The liver has a wide range of functions,including detoxification of various metabolites,protein synthesis,the production of biochemicals necessary for digestion,regulation of glycogen storage,decomposition of red blood cells and hormone production.Liver diseases are originally developed from chronic liver injury,which cause world wide public health concerns.Hepatic fibrosis is an important pathological change of chronic liver injury,and it is caused by persistent chronic injury.Hepatic fibrosis is characterized by the activation of hepatic stellate cells,the dysregulation in the generation and degradation of extracellular matrix(ECM),and the excessive deposition and compositional changes of ECM.Liver fibrosis is a reversible disease,however,the liver cirrhosis or liver cancer is irreversible.Therefore,the early treatment of the chronic liver injury at liver fibrosis stage is important in the prevetion of liver cirrhosis,liver cancer.Currently,the clinical treatment of liver fibrosis is mainly by drugs,but they lack selectivity and cause lots of side effects.In order to compensate for the shortcomings of drug therapy,and with full use of stem cell therapy,drugs contain AMD3100 and FK506 and their combination were used to mobilize endogenous bone marrow stem cells to ameliorate liver fibrosis in rats.To compare the three stratigies in the treatment of liver fibrosis,liver fibrosis model were constucted by intraperitoneal injection of carbon tetrachloride into Sprague Dawley rats.The effects were compared by biochemical examination,the pathological examination of peripheral blood,pathological and histological analysis of the liver tissue sections and the mobilization and plantation of stem cells.The underlying molecular mechanisms for these treatments were studied using real-time quantitative PCR and Western blotting techniques.This paper made three conclusions: 1.The combination therapy ameliorates liver fibrosis in rats;2.The combination therapy inhibites the TGF-β/Smad signaling pathway by FK506,and reduces the inflammation in liver;3.The combination therapy increases STAT3 phosphorylation levels by AMD3100,and promotes liver regeneration.This work provided a starting point for future studies of stem cell mobilization in the treatment of chronic liver injury.