Tissue factor-dependent procoagulant activity of isolated human hepatocytes: relevance to liver cell transplantation

Liver cell transplantation (LCT) aims to correct inborn liver function defects by infusing metabolically active cells into the diseased liver. Further improvement in LCT might depend on the prevention of early loss of transplanted cells. As tissue factor (TF)-dependent activation of coagulation was found to contribute to a low rate of beta cell engraftment in islet transplantation, we investigated the potential procoagulant activity (PCA) of hepatocyte preparations. TF expression on hepatocyte preparations was assessed by flow cytometry, reverse-transcription polymerase chain reaction and immunofluorescence. PCA depending on TF was evaluated in human plasma and in whole blood systems. Coagulation parameters were followed by routine techniques in a LCT recipient Crigler-Najjar patient. We determined that hepatocytes express soluble and membrane-bound forms of TF. We showed that hepatocytes exert a TF-dependent PCA. In parallel, delayed increase in D-dimer levels was observed following the hepatocyte infusions in the Crigler-Najjar patient. Furthermore, in vitro experiments demonstrated that TF-dependent PCA of hepatocytes is inhibited by N-acetyl-L-cysteine. In conclusion, hepatocytes exert TF-dependent PCA, which may contribute to early loss of infused cells. Addition of N-acetyl-L-cysteine to the suspensions of hepatocytes might be beneficial in LCT by inhibiting activation of coagulation.