PhD Scientific Days 2026

Pathological and Oncological Sciences 2.

Rat Liver Regeneration and Cellular Senescence

Name of the presenter

Váncza, Lóránd

Institute/workplace of the presenter

Pediatric Center Tűzoltó street Department Semmelweis University, Faculty of Medicine

Authors

Lóránd Váncza¹, Mano Hunyady², Manuela Juhász²
1: Pediatric Center Tűzoltó street Department Semmelweis University, Faculty of Medicine
2: Department of Pathology and Experimental Cancer Research Semmelweis University, Faculty of Medicine

Text of the abstract

Introduction
The liver is well known for its exceptional regenerative capacity, achieved either by hepatocyte proliferation or by regeneration from progenitor cells. While it is commonly assumed that the original structure and function is recovered in regenerated livers, our results challenge this notion.
Our previous studies have shown that in regenerated liver: (I) the size of the lobules increases and the vasculature changes; (II) the pericentral hypoxic zone expands; (III) the responsiveness to repeated regenerative stimuli decreases; and (IV) the vulnerability to chemical injuries increases. Cellular senescence is a widely studied biological phenomenon which can be brought about by proliferation (replicative senescence).
Aims
This study examined the proportion of senescent cells in regenerated livers, compared with control ones.
Methods
Experiments were performed on male F344 rats, comparing control and regenerated livers. Hepatocyte-driven regeneration was induced by 70% partial hepatectomy (PH), while progenitor cell-driven regeneration was elicited by the combination of surgical hepatectomy with 2-acetylaminofluorene treatment (AAF/PH). Senescent cells were identified on frozen sections by X-gal enzymehistochemistry. Following scanning, the positive area (senescent cells with increased enzymatic activity) was quantified using SlideViewer and ImageJ softwares.
Results
Senescent cells comprised 0.59% (±0.055%) of the section area in the control group. This proportion was significantly higher in PH (0.85% ±0.071%) and AAF/PH (0.93% ±0.121%) treated livers compared to the controls.
Conclusions
The proportion of senescent cells increases in the regenerated liver. In addition to their reduced proliferative capacity, senescent cells are characterized by the secretion of numerous biologically active molecules, known as the senescence-associated secretory phenotype, which significantly influences their microenvironment. The higher proportion of senescent cells may contribute to the altered behavior of regenerated livers. Since liver regeneration also occurs in clinical settings, such as after liver resection or split-liver transplantation, these findings may be highly relevant in a clinical context.
Funding: NKFIH FK 138673
e-mail address: vancza.lorand@semmelweis.hu
University: Semmelweis University, Budapest
Supervisor: Prof. Dr. Katalin Dezső