Ros-Tarraga Patricia, Villanueva-Badenas Estela, Sanchez-Gonzalez Estela, Gallego-Ferrer Gloria, Donato M Teresa, Tolosa Laia
Experimental Hepatology Unit, Health Research Institute La Fe (IISLAFE), Valencia, Spain.
Faculty of Medicine and Dentistry, Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain.
Front Cell Dev Biol. 2025 Apr 30;13:1567916. doi: 10.3389/fcell.2025.1567916. eCollection 2025.
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 stellate-like 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 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.
肝纤维化被认为是影响慢性肝病患者预后的最重要预测指标。它由细胞外基质成分异常积聚所定义，这种积聚源于坏死和炎症过程，最终损害器官功能。由于尚无获批的治疗方法，直接源自患者细胞的综合细胞模型对于理解纤维化背后的机制以及对抗纤维化治疗的反应至关重要。原代人细胞、人肝细胞系以及人干细胞衍生的肝星状样细胞已被广泛用于研究纤维化发病机制。在本文中，我们描述了纤维化发病机制过程中的细胞间相互作用以及细胞外基质的作用，并总结了从简单单层培养到多细胞三维培养的不同模型，这些模型用于更深入地理解该疾病及其治疗反应的机制，同时讨论了它们在肝纤维化建模方面的主要优缺点。
