Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2017; 23(10): 1764-1770
Published online Mar 14, 2017. doi: 10.3748/wjg.v23.i10.1764
Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection
Fabio Marongiu, Michela Marongiu, Antonella Contini, Monica Serra, Erika Cadoni, Riccardo Murgia, Ezio Laconi
Fabio Marongiu, Michela Marongiu, Antonella Contini, Monica Serra, Erika Cadoni, Riccardo Murgia, Ezio Laconi, Experimental Medicine Unit, Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy
Author contributions: Marongiu F, Marongiu M and Laconi E substantially contributed to the conception and design of the study, critical analysis and interpretation of data; all authors designed and performed the experiments, and contributed to the acquisition and analysis of data, made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by Italian Association for Cancer Research, No. IG 14640.
Institutional review board statement: The study was reviewed and approved by the University of Cagliari Institutional Review Board.
Institutional animal care and use committee statement: All animal studies described in this manuscript were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Cagliari.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Correspondence to: Fabio Marongiu, PhD, Experimental Medicine Unit, Department of Biomedical Sciences, University of Cagliari, Via Porcell 4, IV floor, 09124 Cagliari, Italy. fabiomarongiu@unica.it
Telephone: +39-70-6758683 Fax: +39-70-662574
Received: November 10, 2016
Peer-review started: November 13, 2016
First decision: December 19, 2016
Revised: December 27, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: March 14, 2017
Processing time: 122 Days and 23.7 Hours
Abstract
AIM

To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss.

METHODS

The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH.

RESULTS

Liver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration.

CONCLUSION

Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

Keywords: Liver regeneration; Hypertrophy; Hyperplasia

Core tip: The ability of the liver to regenerate is remarkable on both clinical and biological grounds. It is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system during the regenerative response elicited by 2/3 partial hepatectomy (PH) in rats. Analysis of cluster size distribution revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes returned to control values throughout the regenerative process. Thus, hyperplasia stands as the major mechanism contributing to liver mass restoration after PH.