Regeneration and cell recruitment in an improved heterotopic auxiliary partial liver transplantation model in the rat

Yoshihiro Ono, Angelica Pérez-Gutiérrez, Mladen I. Yovchev, Kentaro Matsubara, Shinichiro Yokota, Jorge Guzman-Lepe, Kan Handa, Alexandra Collin De L'Hortet, Angus W. Thomson, David A. Geller, Hiroshi Yagi, Michael Oertel, Alejandro Soto-Gutierrez

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background. Auxiliary partial liver transplantation (APLT) in humans is a therapeutic modality used especially to treat liver failure in children or congenital metabolic disease. Animal models of APLT have helped to explore therapeutic options. Though many groups have suggested improvements, standardizing the surgical procedure has been challenging. Additionally, the question of whether graft livers are reconstituted by recipient-derived cells after transplantation has been controversial. The aim of this study was to improve experimental APLT in rats and to assess cell recruitment in the liver grafts.Methods. To inhibit recipient liver regeneration and to promote graft regeneration, we treated recipients with retrorsine and added arterial anastomosis. Using green fluorescence protein transgenic rats as recipients, we examined liver resident cell recruitment within graft livers by immuno-fluorescence costaining. Results. In the improved APLT model, we achieved well-regenerated grafts that could maintain regeneration for at least 4 weeks. Regarding the cell recruitment, there was no evidence of recipient-derived hepatocyte, cholangiocyte, or hepatic stellate cell recruitment into the graft. Macrophages/monocytes, however, were consistently recruited into the graft and increased over time, which might be related to inflammatory responses. Very few endothelial cells showed colocalization of markers.Conclusions.We have successfully established an improved rat APLT model with arterial anastomosis as a standard technique. Using this model, we have characterized cell recruitment into the regenerating grafts.

Original languageEnglish
Pages (from-to)92-100
Number of pages9
JournalTransplantation
Volume101
Issue number1
DOIs
Publication statusPublished - 2017 Jan

ASJC Scopus subject areas

  • Transplantation

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    Ono, Y., Pérez-Gutiérrez, A., Yovchev, M. I., Matsubara, K., Yokota, S., Guzman-Lepe, J., Handa, K., De L'Hortet, A. C., Thomson, A. W., Geller, D. A., Yagi, H., Oertel, M., & Soto-Gutierrez, A. (2017). Regeneration and cell recruitment in an improved heterotopic auxiliary partial liver transplantation model in the rat. Transplantation, 101(1), 92-100. https://doi.org/10.1097/TP.0000000000001511