The Treatment And Mechanism Of HuMSC-HNF4? In Acute Liver Failure

Background and Objective: Liver failure is a serious liver dysfunction caused by many factors,and currently the only effective treatment is liver transplantation.In recent years,advances in stem cell research for the treatment of liver failure provide a new feasible solution.Hepatocyte nuclear factor 4?(HNF4?)is an important nuclear transcription factor in promoting liver cell differentiation and maturation and maintenance of normal physiological function of liver cells play a crucial role.Recent studies have demonstrated that the expression of hepatocyte nuclear HNF4? reset within the damaged liver cells can restore normal physiological function.Methods: Human umbilical cord mesenchymal stem cells(HuMSC)were cultured in vitro and transfected by lentivirus expressing HNF4?(hereinafter referred to as HuMSC-HNF4?).By intraperitoneal injection for the treatment of D-galactosamine / lipopolysaccharide(D-galn / LPS)induced acute liver failure in mouse models and in vitro experimental study HuMSC-HNF4? by regulating the liver macrophages(Kupffer cells)for further mechanism research.Results: HuMSC-HNF4? significantly improved the survival of mice with acute liver failure,inhibited the liver cell damage and macrophage infiltration,and reduced the levels of liver enzymes and inflammatory factors.For further research discovery mechanism,HuMSC-HNF4? Kupffer cells may promote the M2 type polarization;inhibit macrophage inflammatory response to LPS,and reduce levels of TNF-?,IL-1? and other inflammatory factors.Conclusion: HuMSC-HNF4? protected acute liver failure by regulating Kupffer cell polarization,prompting its type to M2 polarization,inhibited macrophage inflammatory response,and reduced levels of TNF-?,IL-1? and other inflammatory factors,reduced the liver damage.This study found that the treatment of liver failure HuMSC-HNF4? role different from the previous passive support,but suppressing the overinflammation in the body,which provided a new idea for future research and clinical practice.