94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
REVIEW article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1567916
This article is part of the Research TopicStem Cell Research and Therapy for Liver and Kidney DiseasesView all 4 articles
Challenges of in vitro modelling of liver fibrosis
Provisionally accepted
Patricia Ros-Tarraga1Estela Villanueva-Badenas1,2Estela Sanchez-Gonzalez3
Gloria Gallego-Ferrer3,4M. Teresa Donato1,2,5*
Laia Tolosa1,4*- 1La Fe Health Research Institute, Valencia, Spain
- 2Department of Biochemistry and Molecular Biology, Faculty of Medicine and Dentistry, University of Valencia, Valencia, Spain
- 3Center for Biomaterials and Tissue Engineering, Polytechnic University of Valencia, Valencia, Valencia, Spain
- 4Center for Biomedical Research in the Network in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Madrid, Spain
- 5Network Biomedical Research Center (CIBERehd), Madrid, Madrid, Spain
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Liver fibrosis has been proposed as the most important predictive indicator affecting prognosis of patients with chronic liver disease. It is defined by an abnormal accumulation of extracellular matrix components that results from necrotic and inflammatory processes and eventually impairs organ function. With no approved therapy, comprehensive cellular models directly derived from patient's cells are necessary to understand the mechanisms behind fibrosis and the response to anti-fibrotic therapies. Primary human cells, human hepatic cell lines and human stem cells-derived hepatic stellatelike cells have been widely used for studying fibrosis pathogenesis. In this paper, we depict the cellular crosstalk and the role of extracellular matrix during fibrosis pathogenesis and summarize different in vitro models from simple monolayers to multicellular 3D cultures used to gain deeper mechanistic understanding of the disease and the therapeutic response, discussing their major advantages and disadvantages for liver fibrosis modelling.
Keywords: liver fibrosis, extracellular matrix, in vitro systems, 3D models, therapies three-dimensional, SMA: -smooth muscle actin, FFA: free fatty acids, HSC: Hepatic stellate cells, iPSC: induced pluripotent stem cell, KC: Kupffer cell, LPS: lipopolysaccharide, LSECs: Liver Sinusoidal Endothelial Cells
Received: 28 Jan 2025; Accepted: 10 Apr 2025.
Copyright: © 2025 Ros-Tarraga, Villanueva-Badenas, Sanchez-Gonzalez, Gallego-Ferrer, Donato and Tolosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
M. Teresa Donato, Department of Biochemistry and Molecular Biology, Faculty of Medicine and Dentistry, University of Valencia, Valencia, 46010, Spain
Laia Tolosa, La Fe Health Research Institute, Valencia, Spain
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.