Transplantation of fetal liver FLK-1+ cells in treatment of acute liver injury

Background: Previous studies of our research group have shown that FLK-1+ cells existed in the mouse fetal liver at embryonic 17-19 days, and they expressed embryonic stem cells and presented multi-differentiation potentials. Objective: To evaluate the therapeutic effect of the transplantation of FLK-1+ cells derived from mouse fetal liver on acute liver injury in mice. Methods: The FLK-1+ fraction were enriched from the fetal liver with immunomagnetic beads method and detected by flow cytometry. The Oct-3/4 and Rex-1 genes in FLK-1+ cells were detected by reverse transcription-polymerase chain reaction. The FLK-1+ cells were induced to differentiate into liver cells by hepatocyte growth factor and epidermal growth factor. The model of acute liver injury in mice was established by intraperitoneally injecting carbon tetrachloride 4, and was randomly divided into two groups. In the control group, mouse models with acute liver injury were infused normal saline via tail vein; in the experimental group, mouse models with acute liver injury were infused induced FLK-1+ cells (1×106) via tail vein. The blood was collected at 16 hours and liver functions were detected. The mortality of mice was observed at 64 hours. Results and Conclusion: The fetal liver FLK-1+ cells highly expressed Oct-3/4 and Rex-1 mRNA, and albumin expressing rate in FLK-1+ cells was 0.6%. After induced by hepatocyte growth factor for 3 days, FLK-1 did not express. After induced by hepatocyte growth factor and epidermal growth factor for 3 days, Oct-3/4 and Rex-1 mRNA expression was significantly reduced or disappeared in FLK-1+ cells, and 96.38% FLK-1+ cells expressed albumin. After FLK-1+ cells induced for 3 days were transplanted to mouse models with acute liver injury for 16 hours, the serum glutamic-oxalacetic transaminease and glutamic-pyruvic transaminase were significantly lower (P < 0.05), but serum albumin was significantly higher than the control group (P < 0.05). However, serum total bilirubin and fibrinogen showed no significant differences between two groups (P > 0.05). The mortality rate in the control group was 80% and the mortality rate in the experimental group was 61.5% at 64 hours, with no significant difference between two groups (P > 0.05). Experimental findings indicate that, transplanting fetal liver FLK-1+ cells induced by hepatocyte growth factor and epidermal growth factor for 3 days can improve liver cells function in mice with acute liver damage.