Extensive chimerism in liver transplants: Vascular endothelium, bile duct epithelium, and hepatocytes

Abstract

The transplanted liver has been shown to be particularly capable of inducing tolerance. An explanation may be the presence of chimerism. Cells of donor origin have been found in recipient tissues after transplantation of any solid organ. Evidence for the presence of cells of recipient origin within the transplanted liver is very limited. We investigated whether nonlymphoid cells of recipient origin can be found within human liver allografts. Five male patients who received a liver transplant from a female donor and 11 patients who received an HLA-I mismatched liver transplant were studied. We confirmed our observations with two different techniques in combination with double-staining techniques. To identify male cells in female liver transplants, we used in situ hybridization for sex chromosomes. To identify specific HLA class I antigens of recipient origin, we used immunohistochemistry with HLA class I-specific antibodies. Double staining was performed to discriminate different cell lineages and inflammatory cells. Endothelial cells of recipient origin were found in 14 of 16 donor livers. Bile duct epithelial cells of recipient origin were found in 5 of 16 cases. Hepatocytes of recipient origin were seen in only 1 of the 5 studied sex-mismatched donor livers. Our study provides evidence that cells of recipient origin can replace biliary epithelial cells, endothelial cells, and hepatocytes within the human liver allograft. This is consistent with the concept that circulating pluripotent progenitor cells exist, capable of differentiating into endothelial cells, epithelial cells, and hepatocytes.