Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2021; 13(10): 1595-1609
Published online Oct 26, 2021. doi: 10.4252/wjsc.v13.i10.1595
Impact of senescence on the transdifferentiation process of human hepatic progenitor-like cells
Francesco Bellanti, Giorgia di Bello, Rosanna Tamborra, Marco Amatruda, Aurelio Lo Buglio, Michał Dobrakowski, Aleksandra Kasperczyk, Sławomir Kasperczyk, Gaetano Serviddio, Gianluigi Vendemiale
Francesco Bellanti, Giorgia di Bello, Rosanna Tamborra, Marco Amatruda, Aurelio Lo Buglio, Gaetano Serviddio, Gianluigi Vendemiale, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy
Michał Dobrakowski, Aleksandra Kasperczyk, Sławomir Kasperczyk, Department of Biochemistry, Medical University of Silesia, Zabrze 41-808, Poland
Author contributions: Bellanti F and Vendemiale G designed and coordinated the study; Bellanti, F, di Bello G, Tamborra R, Lo Buglio A, Amatruda M, Dobrakowsky M, and Kasperczyk A performed the experiments, acquired, and analyzed data; Bellanti, F, di Bello G, Tamborra R, Amatruda M, Lo Buglio A, Dobrakowsky M, Kasperczyk A, Kasperczyk S, Serviddio G, and Vendemiale G interpreted the data; Bellanti F wrote the manuscript; Kasperczyk S, Serviddio G, and Vendemiale G supervised the manuscript; All authors approved the final version of the article.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at the University of Foggia.
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: No additional data are available.
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: Francesco Bellanti, MD, PhD, Doctor, Associate Professor, Department of Medical and Surgical Sciences, University of Foggia, viale Pinto 1, Foggia 71122, Italy. francesco.bellanti@unifg.it
Received: April 26, 2021
Peer-review started: April 26, 2021
First decision: May 12, 2021
Revised: June 14, 2021
Accepted: August 23, 2021
Article in press: August 23, 2021
Published online: October 26, 2021
Processing time: 182 Days and 11.5 Hours
Core Tip

Core Tip: The human HepaRG cell line represents an effective model for the study of liver metabolism and hepatic progenitors. However, the impact of senescence on HepaRG cells is not known. We characterized the effects of senescence on the transdifferentiation capacity and mitochondrial metabolism of HepaRG cells. By using a replication protocol, we described higher senescence-associated markers and lower transdifferentiation markers in passage 20 (P20) than in P10 cells. Cellular and mitochondrial oxygen consumption, and ATP and nicotinamide adenine dinucleotide (NAD+)/NAD with hydrogen (NADH) content were lower in P20 than in P10 transdifferentiated cells. To conclude, senescence-associated mitochondrial dysfunction may limit the transdifferentiation potential of HepaRG cells.