The role of recipient epithelial cells in regeneration after liver transplantation: Different kinetics of chimerism for hepatocytes and bile duct epithelial cells

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F.J.M. Roos, J.W. Selten, W.G. Polak, M.M.A. Verstegen, H.F.B.M. Sleddens, M. Doukas, H.J. Metselaar, J.N.M Ijzermans, L.J.W. van der Laan

Chair(s): prof. dr. C.C. Baan & Dr. M.B. Rookmaaker

Wednesday 8 march 2017

17:30 - 17:42h at Hendrik Marsmanzaal

Categories: Parallel - Basaal

Parallel session: Parallelsessie V – Basaal 1 - Analyse niet-hematopoietische cellen in orgaantransplantatie

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Impaired regeneration of the biliary tree after liver transplantation has been linked to post-operative biliary complications and, more specific, to non-anastomotic bile duct strictures (NAS). Ischemic damage of stem cell populations in the graft may impair regenerative processes of both hepatocytes and bile duct epithelial cells (cholangiocytes). It has been hypothesized that recipient-derived (stem) cells may contribute to the restoration of the damaged graft and thereby establishing epithelial chimerism. Therefore, the aim of this study is to determine the extent and kinetics of recipient-derived hepatocytes and cholangiocyte repopulation in transplanted livers after graft explantation due to NAS and other reasons.

We retrospectively identified recipients which required a re-transplantation for various indications between 2001 and 2015. Recipient-derived cells in the liver explant were determined using immunohistochemistry for HLA-A2 and X- and Y-chromosome fluorescent in situ hybridization (FISH). Bile ducts were located by cytokeratin 19 staining.

Overall, 13 explants for which a re-transplantation was performed were included in this study, of which five for NAS. All were HLA-A2 positive recipient who received a HLA-A2 negative liver graft. Additionally, four grafts were of female donors transplanted in male recipients. Median time until re-transplantation was 167 days. In all grafts, extensive repopulation of hepatocytes and cholangiocytes by recipient cells was observed. These results were confirmed by XY-FISH analysis. The repopulation of hepatocytes was time dependent. A significant difference was observed between early and late re-transplantations (365; p=0.03). In contrast, the percentage of recipient derived cholangiocytes in the same grafts was not time-dependent (10.8% ±12.9 vs. 8.5% ±8.5; p=0.75). No clear differences in hepatocyte repopulation was observed between NAS and the non-NAS group (11.8% ±9.6 vs. 26.0% ±27.2; p=0.38) though there was a trend toward more cholangiocyte repopulation in the NAS livers (13.8% ±12.7 vs. 3.5% ±4.4 p=0.054).

 

Conclusion: extensive epithelial chimerism occurs after liver transplantation. The kinetics of hepatocyte and cholangiocyte chimerism is significantly different, suggesting distinct underlying regenerative mechanisms.