Issue 9, 2023

In vitro functional models for human liver diseases and drug screening: beyond animal testing

Abstract

Liver is one of the most important and complex organs in the human body, being characterized by a sophisticated microarchitecture and responsible for key physiological functions. Despite its remarkable ability to regenerate, acute liver failure and chronic liver diseases are major causes of morbidity and mortality worldwide. Therefore, understanding the molecular mechanisms underlying such liver disorders is critical for the successful development of novel therapeutics. In this frame, preclinical animal models have been portrayed as the most commonly used tool to address such issues. However, due to significant species differences in liver architecture, regenerative capacity, disease progression, inflammatory markers, metabolism rates, and drug response, animal models cannot fully recapitulate the complexity of human liver metabolism. As a result, translational research to model human liver diseases and drug screening platforms may yield limited results, leading to failure scenarios. To overcome this impasse, over the last decade, 3D human liver in vitro models have been proposed as an alternative to pre-clinical animal models. These systems have been successfully employed for the investigation of the etiology and dynamics of liver diseases, for drug screening, and – more recently – to design patient-tailored therapies, resulting in potentially higher efficacy and reduced costs compared to other methods. Here, we review the most recent advances in this rapidly evolving field with particular attention to organoid cultures, liver-on-a-chip platforms, and engineered scaffold-based approaches.

Graphical abstract: In vitro functional models for human liver diseases and drug screening: beyond animal testing

Article information

Article type
Review Article
Submitted
06 Dec 2021
Accepted
26 Nov 2022
First published
29 Nov 2022
This article is Open Access
Creative Commons BY license

Biomater. Sci., 2023,11, 2988-3015

In vitro functional models for human liver diseases and drug screening: beyond animal testing

A. Paradiso, M. Volpi, C. Rinoldi, N. Celikkin, N. Contessi Negrini, M. Bilgen, G. Dallera, F. Pierini, M. Costantini, W. Święszkowski and S. Farè, Biomater. Sci., 2023, 11, 2988 DOI: 10.1039/D1BM01872H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements