Ex Vivo Tools and Models in MASLD Research

Abstract

Metabolic dysfunction-associated fatty liver disease (MASLD) presents a growing global health challenge with limited therapeutic choices. This review delves into the array of ex vivo tools and models utilized in MASLD research, encompassing liver-on-a-chip (LoC) systems, organoid-derived tissue-like structures, and human precision-cut liver slice (PCLS) systems. Given the urgent need to comprehend MASLD pathophysiology and identify novel therapeutic targets, this paper aims to shed light on the pivotal role of advanced ex vivo models in enhancing disease understanding and facilitating the development of potential therapies. Despite challenges posed by the elusive disease mechanism, these innovative methodologies offer promise in reducing the utilization of in vivo models for MASLD research while accelerating drug discovery and biomarker identification, thereby addressing critical unmet clinical needs.

Keywords: ex vivo models; ex vivo precision-cut liver slice (PCLS); liver-on-a-chip (LoC); metabolic dysfunction-associated fatty liver disease (MASLD); organoids.

Figure 1

Overview of ex vivo liver models: The diagram highlights three common ex vivo liver models: Liver Organoids, Precision-Cut Liver Slice (PCLS) Systems, and Liver-on-a-Chip (LoC). Each model has distinct advantages and disadvantages. Liver organoids are multicellular and can be easily adapted or augmented, allowing long-term temporal studies with more available material. PCLS systems preserve tissue architecture but may suffer from variability. LoC technology provides a more physiologically relevant microenvironment, but limitations include lack of vascularization and absence of peripheral immune components. These models collectively contribute to advancing liver research, with varying suitability based on experimental needs.