Re-evaluation of hepatocyte replacement by recipient-derived cells after allogenic liver transplantation: Discrepancy between clinical observations and a rat model

Hepatol Res. 2016 Sep;46(10):1037-44. doi: 10.1111/hepr.12643. Epub 2016 Feb 16.


Aim: Reports suggest that hepatocyte replacement by recipient-derived cells is an active phenomenon after allogenic liver transplantation in rats. However, this phenomenon is rarely observed in humans, and further evaluation is necessary to bridge the gap between clinical practice and animal experiment.

Methods: Fifty percent volume of the liver from green fluorescent protein (GFP) transgenic Lewis rats were transplanted into wild-type Dark Agouti (DA) rats, in which GFP negative hepatocytes were considered as host (DA rat)-derived cells. The transplanted liver was observed on whole imaging system and fluorescent microscope 7-10 days after transplantation. As a different method from previous reports, hepatocytes isolated from transplanted livers were cultured, and the expression of GFP was examined.

Results: The sliced liver (2 mm) after allogenic transplantation demonstrated decreased intensity of GFP signals compared with the positive control. The hematoxylin-eosin staining of the section revealed abundant infiltration of inflammatory cells, suggesting an immunological rejection reaction. Large polygonal cells with significantly decreased or negative GFP signals were also demonstrated, which was consistent with the results of previous studies. However, cell culturing demonstrated that none of the examined albumin positive large polygonal cells were host-derived cells. The same results were obtained irrespective of reconstruction of hepatic artery.

Conclusion: Our result implies that rejection reaction does not promote parenchymal replacement by recipient-derived cells, in contrast to previous reports. If so, the phenomena occurring in rats are consistent with clinical observation of liver transplantation in humans.

Keywords: hepatocyte; rat; repopulation; transplantation.