Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2020; 26(27): 3899-3916
Published online Jul 21, 2020. doi: 10.3748/wjg.v26.i27.3899
Liver structural transformation after partial hepatectomy and repeated partial hepatectomy in rats: A renewed view on liver regeneration
Keti Tsomaia, Leila Patarashvili, Nino Karumidze, Irakli Bebiashvili, Elza Azmaipharashvili, Irina Modebadze, Diana Dzidziguri, Marom Sareli, Sergey Gusev, Dimitri Kordzaia
Keti Tsomaia, Leila Patarashvili, Nino Karumidze, Irakli Bebiashvili, Elza Azmaipharashvili, Dimitri Kordzaia, Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
Irina Modebadze, Diana Dzidziguri, Faculty of Exact and Natural Sciences, Ivane Javakhishvili Tbilisi State University, Tbilisi 0179, Georgia
Marom Sareli, Department of Surgical Oncology (Surgery C), Chaim Sheba Medical Center at HaShomer, Tel Aviv 52621, Israel
Sergey Gusev, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia
Dimitri Kordzaia, Clinical Anatomy and Operative Surgery, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
Author contributions: Tsomaia K and Patarashvili L were responsible for planing experiments, the preparation and evaluation of histological slides, for mor-phometrical, literature search, in data interpretation and manuscript drafting; Karumidze N and Modebadze I were responsible for determination of the DNA concentration of the hepatocytes; Bebiashvili I and Azmaipharashvili E contributed in experiments, in literature search and review and in analysis of the results. Dzidziguri D and Sareli M contributed in planning the experiments and research methodology, in data analysis, manuscript drafting and revision; Gusev S performed SEM investigation, evaluation, description, data analysis, editing and revision of the manuscript; Kordzaia D performed the conceptualization of research, project administration, supervision of experiments and investigation of SEM. Control preparation of the last version of the manuscript; all authors reviewed and approved the final version to be published.
Supported by the Shota Rustaveli National Science Foundation of Georgia, No. DP2016_22 [New Interfaculty Interdisciplinary Structured Doctoral Programme “Translational Biomedicine” (Direction – “ Hepatology” )].
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board (the Ethical Committee) of Aleksandre Natishvili Institute of Morphology, Tbilisi State University.
Institutional animal care and use committee statement: The experimental study was reviewed by bioethical committee of Aleksandre Natishvili Institute of Morphology, Tbilisi State University and approved that this study fully corresponds with EU Directive 2010/63/EU “on the protection of animals used for scientific purposes”.
Conflict-of-interest statement: The authors declare that they have no competing interests. The authors do not have any commercial or collaborative relationships that could be constructed as biased or inappropriate.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared according to these guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Dimitri Kordzaia, DSc, MD, PhD, Dean, Professor, Clinical Anatomy and Operative Surgery, Ivane Javakhishvili Tbilisi State University, Beliashvili str. 78, Tbilisi 0159, Georgia. dimitri.kordzaia@tsu.ge
Received: February 27, 2020
Peer-review started: February 27, 2020
First decision: April 30, 2020
Revised: May 12, 2020
Accepted: June 23, 2020
Article in press: June 23, 2020
Published online: July 21, 2020
Processing time: 144 Days and 22.4 Hours
Abstract
BACKGROUND

The phenomenon of liver regeneration after partial hepatectomy (PH) is still a subject of considerable interest due to the increasing frequency of half liver transplantation on the one hand, and on the other hand, new surgical approaches which allow removal of massive space-occupying hepatic tumors, which earlier was considered as inoperable. Interestingly, the mechanisms of liver regeneration are extensively studied after PH but less attention is paid to the architectonics of the regenerated organ. Because of this, the question “How does the structure of regenerated liver differ from normal, regular liver?” has not been fully answered yet. Furthermore, almost without any attention is left the liver's structural transformation after repeated hepatectomy (of the re-regenereted liver).

AIM

To compare the architectonics of the lobules and circulatory bed of normal, re-generated and re-regenerated livers.

METHODS

The livers of 40 adult, male, albino Wistar rats were studied. 14 rats were subjected to PH - the 1st study group (SG1); 10 rats underwent repeated PH – the 2nd study group (SG2); 16 rats were subjected to sham operation - control group (CG); The livers were studied after 9 months from PH, and after 6 months from repeated PH. Cytological (Schiff reaction for the determination of DNA concen-tration), histological (H&E, Masson trichrome, CK8 Immunohistochemical marker, transparent slides after Indian Ink injection, ), morphometrical (hepatocytes areas, perimeters and ploidy) and Electron Microscopical (Scanning Electron Microscopy of corrosion casts) methods were used.

RESULTS

In the SG1 and SG2, the area of hepatocytes and their perimeter are increased compared to the CG (P < 0.05). However, the areas and perimeters of the hepatocytes of the SG1 and SG2 groups reveal a lesser difference. In regenerated (SG1) and re-regenerated (SG2) livers, the hepatocytes form the remodeled lobules, which size (300-1200 µm) exceeds the sizes of the lobules from CG (300-600 µm). The remodeled lobules (especially the “mega-lobules” with the sizes 1000-1200 µm) contain the transformed meshworks of the sinusoids, the part of which is dilated asymmetrically. This meshwork might have originated from the several portal venules (interlobular and/or inlet). The boundaries between the adjacent lobules (including mega-lobules) are widened and filled by connective tissue fibers, which gives the liver parenchyma a nodular look. In SG2 the unevenness of sinusoid diameters, as well as the boundaries between the lobules (including the mega-lobules) are more vividly expressed in comparison with SG1. The liver tissue of both SG1 and SG2 is featured by the slightly expressed ductular reaction.

CONCLUSION

Regenerated and re-regenerated livers in comparison with normal liver contain hypertrophied hepatocytes with increased ploidy which together with transformed sinusoidal and biliary meshworks form the remodeled lobulli.

Keywords: Partial hepatectomy; Repeated hepatectomy; Liver regeneration; Liver re-regeneration; Hepatocytes hypertrophy; Remodeling; Ploidy; Corrosion casts

Core tip: Liver regeneration after partial hepatectomy (PH) is based on both proliferation and hypertrophy of hepatocytes. These cells unite into remodeled lobules, the sizes of which vary widely. The microcirculation of the liver is also re-modeled. At the same time, there is a suspicion that hyperplasia-hypertrophy and remodeling do not apply to all hepatocytes and all lobules; it is also possible that, in parallel with remodeling, new lobules are formed. After repeated PH, liver regeneration is based on the same type of transformations, although their intensity is less. To fully evaluate the lobular and microcirculatory architecture of regenerated liver after both, PH and repeated PH, it is necessary to investigate the architectonics of the initials of the biliary system.