The Treatment And Mechanism Of HuMSC-HNF4α 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 4α(HNF4α)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 HNF4α 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 HNF4α(hereinafter referred to as HuMSC-HNF4α).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-HNF4α by regulating the liver macrophages(Kupffer cells)for further mechanism research.Results: HuMSC-HNF4α 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-HNF4α Kupffer cells may promote the M2 type polarization;inhibit macrophage inflammatory response to LPS,and reduce levels of TNF-α,IL-1β and other inflammatory factors.Conclusion: HuMSC-HNF4α protected acute liver failure by regulating Kupffer cell polarization,prompting its type to M2 polarization,inhibited macrophage inflammatory response,and reduced levels of TNF-α,IL-1β and other inflammatory factors,reduced the liver damage.This study found that the treatment of liver failure HuMSC-HNF4α 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.