Background: Amnion-derived cells are promising for clinical application as cell sources with multi-differentiation potential, and one promising transplantation route is considered to be intraportal transplantation. However, it has yet to be clarified whether amnion-derived cells would induce an immediate inflammatory response, an obstacle for cell engraftments in islet and hepatocyte transplantation.
Methods: The expression of tissue factor, a potent pro-coagulation factor, on isolated human amnion epithelial cells (hAECs) was analyzed by flow cytometry. To evaluate coagulation activation in vivo, hAECs were transplanted intraportally in male rats, and thrombin antithrombin (TAT) was serially measured. For assessing the engraftment and function of hAECs as a substitute for hepatocytes, hAECs were transplanted into non-albumin rats, blood samples were collected until day 21, and human albumin level in serum was measured. Rat livers were removed and histologically investigated.
Results: Flow cytometry analysis showed that hAECs constantly expressed tissue factors irrespective of cryopreservation. Plasma TAT level was significantly elevated after intraportal hAEC transplantation, and the TAT elevation was suppressed by heparin infusion. The human albumin level in non-albumin rats increased after intraportal hAEC infusion. Histological examination revealed that albumin-positive cells were identified in the explanted liver on day 21 after transplantation.
Conclusion: We confirmed that hAECs expressed tissue factors on the surface, and hAEC transplantation caused coagulation activation, which could lead to instant blood-mediated inflammatory reactions. Although heparin suppressed the coagulation activation, the effects of promoting hAEC engraftment remain to be elucidated.