| With the progress of science and technology and the development ofeconomy, people life rhythm becomes faster, and material life quality is elevated,however, people’s health become frequently problems. Virus infection, alcoholism ordrugs can cause liver damage that often results in chronic liver disease mainly due toliver cell degeneration, necrosis and fibrosis. Furthermore, many patients eventuallydevelope into irreversible liver cirrhosis and even hepatocellular carcinoma thatserious endanger the health and life of patients. At the early stage, the liver injury andfibrosis are both reversible and medicable. Timely an intervention via promoting livercell regeneration and inhibiting fibrosis is the key to treat liver injury. Hepatocytegrowth factor (HGF), one of the most important cytokines in liver development andregeneration, can promote liver cell regeneration, inhibit fibrosis and induce stemcells differentiation into liver cells. HGF is now considered the first choice in thetreatment of chronic liver disease. Keratinocyte growth factor (KGF) and its receptorKGFR play important roles in many epithelial proliferation, migration, differentiationand repair processes, including the skin, intestine, stomach, lung, prostate, breast,cornea, thymus and so on. At present, KGF has significant effect in the treatment ofvarious diseases, new treatment methods based on KGF are constantly emerging.Mesenchymal stem cells (MSCs) can be multi-directional differentiated, and can behomed in the injury site to participate in the restoration of demaged tissues. So MSCsalso have an important role in the regeneration and repair of injuried liver cells.In this study, human umbilical cord MSCs were modified with recombinantadenoviruses carrying human HGF gene and its therapeutic effects were evaluated bya liver injure rat model induced by carbon tetrachloride so as to provide a newexperimental evidence for the treatment of chronic liver disease.Human umbilical cord mesenchymal stem cells were separated and amplified byan adherent culture method and the multiplicity of infection (MOI) of recombinantadenovirus was determined by recombinant adenoviruses carrying green fluorescentprotein gene (Ad-GFP). When the multiplicity of infection is150, about91.36%ofMSCs were infected, and HGF expression, detected by ELISA, reached to148.5ng/ml,after MSCs were infected with Ad-HGF. In view of the above results, the MSCsinfected by150MOI of Ad-HGF for48h were chosen to treat the rats with chronic liver injury induced by CCl4.After the chronic liver injury was induced by CCl4,and the rats were treated withAd-HGF, MSC or HGF/MSC by tail vein injection. After five weeks of treatment, thetherapeutic effects were evaluated. The results of fatty degeneration and function ofliver showed that rat liver injury model was developed after induced with CCl4-oliveoil solution for4weeks. Any side effect was not observed in rats after injection withcells. However, compared with the model group, the body weight of rats in threetreatment groups increased significantly after therapy for4weeks and the liver indexdecreased, moreover, the survival rate obviously increased (Model：50%，MSCs：70%，Ad-HGF：70%，HGF/MSCs：90%). The liver function of rats in HGF/MSCsgroups was improved markedly compared with model group, indication by theincrease of alanine aminotransferase and aspartate aminotransferase activities, thedecrease of serum total bilirubin, and the increase of serum albumin as well. Incontrast, only the aspartate aminotransferase activity in MSCs group was lower than itin model group. Moreover, the quantities of malondialdehyde indicated that theperoxidatic reaction in the liver tissues of treatment groups was amelioratedsignificantly compared with model group. Furthermore, the results of hydroxyprolinedemonstrated that the treatment with HGF/MSCs and MSCs may attenuate thefibrosis of liver.The liver injury model induced by carbon tetrachloride is improved, based onHGF/MSC treatment of liver injury. Animals’ liver damage were alleviated and weretreated with KGF/MSC. The results showed that KGF/MSCs also have therapeuticeffect on liver injury, can restore the liver injury animal weight, improve liverfunction, reduce the liver steatosis and fibrosis.Conclusion: The liver injury induced by CCl4-olive oil solution was amelioratedwith administration with MSCs, Ad-HGF or HGF/MSCs and the therapeutic effect ofHGF/MSCs was better. KGF/MSCs can restore the liver injury animal weight,improve liver function, reduce the liver steatosis and fibrosis.The results of this studymay provide a new treatment for live injury. |
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