Abstract:Objective: To investigate the reparative effect of HNF4α embryonic hepatic stem cells on acute hepatic injury.
Methods: Suspension of ED 14 Fischer (F) 344 rat embryonic hepatic stem cells was prepared by collagenase digestion and mechanical disaggregation and maintained by long-term culture in vitro. Healthy SD female rats were randomly divided into transplantation group (TP group, n=20) and control group (n=20). The experimental acute hepatic injury was induced by CCl4-lavage. Suspension of embryonic hepatic stem cells was transplanted into injured livers of rats in transplantation group via portal vein while saline of equal volume was used in control group. The levels of ALT and AST in the serum and histopathological injury of hepatic tissues were analyzed 6 h before, and 1w, 3w and 5w after injection. Evaluation of HNF4α protein expression in rat livers by immunohistochemistry and Western blot was performed before and after treatment.
Results: The liver function of control group was slow recovery, as evidenced by significantly increased ALT and AST in serum(P<0.05). By contrast, the injured hepatic tissues were markedly repaired in TP group, and liver function gradually returned to normal level. The survival rate of TP group at 5 weeks was significantly higher than that of control group (P=0.002). After liver injury, expression of HNF4α in the injured liver tissue notably increased. And then, in accordance with the gradual restoration of liver tissue, HNF4α expression was slowly decreased.
Conclusions: HNF4α plays a protective effect in the early stage of hepatic injury after liver transplantation, and it could probably act through promoting the restoration of acute hepatic injury by facilitating the differentiation, proliferation, and migration to damaged hepatic lobule of embryonic hepatic stem cell.