Coagulation activation and hepatic engraftment of human amnion-derived cells after intraportal transplantation in rats

Human amniotic epithelial cells (hAECs) have emerged as a promising cell source for regenerative medicine, with intraportal transplantation as a potential delivery route. However, the extent to which hAECs induce an immediate inflammatory response remains unclear. This study investigated tissue factor (TF) expression in isolated hAECs and assessed coagulation activation following intraportal transplantation in a rat model. TF expression was analyzed before and after cryopreservation, while thrombin - antithrombin (TAT) complex levels were measured to evaluate coagulation activation. To assess engraftment and hepatocyte-like function, hAECs were transplanted into non-albuminemic rats, followed by serial measurements of serum human albumin levels and histological liver analysis. The findings indicate that hAECs express TF pre- and post-cryopreservation. Intraportal transplantation resulted in a significant increase in plasma TAT levels, which was mitigated by heparin administration. Furthermore, human albumin levels increased post-transplantation, and albumin-positive cells were detected in the liver on day 21. These results suggest that intraportal hAEC transplantation is a feasible approach for hepatic engraftment; however, TF expression may trigger coagulation activation, potentially leading to an instant blood-mediated inflammatory reaction. Further research is warranted to optimize anticoagulation strategies and evaluate long-term engraftment efficacy for clinical applications.