PhD Scientific Days 2026

Pathological and Oncological Sciences 1.

Repopulation capacity of hepatocytes from regenerated rat livers

Name of the presenter

Juhász, Mária Manuela

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research Semmelweis University, Faculty of Medicine

Authors

Mária Manuela Juhász¹
1: Department of Pathology and Experimental Cancer Research Semmelweis University, Faculty of Medicine

Text of the abstract

Introduction: It is still widely assumed that regenerated livers do not differ structurally and functionally from healthy ones. However, recent research has identified important structural changes in regenerated livers. Our previous studies demonstrated that liver regeneration in rats results in an increase in lobule size and alterations in vascular architecture, which may have functional consequences.

Aims: We used a retrorsine (RS) model to assess the repopulation capacity of hepatocytes from regenerated and age-matched control rat livers. Hepatocytes and progenitor cells mediated regeneration was investigated as well.

Method: Hepatocytes were isolated via two-step collagenase digestion from F344 DPPIV-positive donor rats (control, hepatocyte-regenerated, and progenitor-mediated groups) and transplanted into F344 DPPIV-negative retrorsine pretreated recipients. Hepatocyte-driven regeneration was induced by surgical partial hepatectomy (PH), while for the progenitor-mediated regeneration we combined PH with 2-acetylaminofluorene treatment (AAF/PH model). The retrorsine pretreatment inhibited host hepatocyte proliferation, thereby providing the donor cells a selective growth advantage. Animals were sacrificed 1 and 5 weeks after transplantation. Frozen liver sections were stained for DPPIV by enzymehistochemistry and analyzed using Slideviewer and ImageJ programs to determine the extent of DPPIV-positivity in relation to the total area of the image.

Results: One week after transplantation, the seeding of the hepatocytes was even in all three groups; although not biologically significant, the engraftment rate was significantly lower in the AAF/PH group. At 5 weeks, hepatocytes from control livers occupied on average 20.01% of the slides, while: 8.48% in the PH group and 3.89% in the AAF/PH group. The differences between control and both regenerated groups were statistically significant (t-test, p<0.05). After five weeks, hepatocytes in the PH group exhibited significantly greater repopulation capacity than those in the AAF/PH group.

Conclusion: The repopulation capacity of the hepatocytes from regenerated liver is decreased. Further studies are required to determine whether the reduced fitness of hepatocytes from regenerated livers reflects impaired proliferation, metabolic dysfunction, or defective functional integration.

Funding: NKFIH FK 138673