Narrative review of in vitro experimental models of hepatic fibrogenesis

Background and Objective: Hepatic fibrosis is a pathological condition affecting millions of people worldwide that results from an improper tissue repair process, following liver injury or inflammation. Since progressive liver fibrosis can evolve into end-stage liver diseases, it is becoming increasingly important to develop efficient experimental models for evaluating new anti-fibrotic therapies. An important role in the onset and progression of hepatic fibrosis is played by hepatic stellate cells (HSCs), perisinusoidal vitamin A-storing cells that, in the presence of pro-fibrogenic stimuli, acquire a myofibroblast-like phenotype with an increased ability to produce extracellular matrix (ECM) components. In this review, we provide an overview of the traditional two-dimensional (2D) systems and of the innovative bioengineered three-dimensional (3D) models that allow for the screening of novel anti-fibrotic therapies. Methods: Data presented in this narrative review were retrieved from scientific literature by searching the computerized database PubMed and MEDLINE for original and review papers describing different in vitro 2D and 3D culture systems that mimic hepatic fibrosis. Key Content and Findings: Over the past years, most in vitro studies have focused on the mechanisms underlying HSC activation, using liver cells cultured in traditional 2D systems. The development of 3D in vitro models allowed studying the complex interactions between HSCs and the surrounding parenchymal and non-parenchymal cells, and between liver cells and ECM, thus improving the mimicking of the situation in vivo. Advanced bioengineered 3D models can replace in vivo models reducing the ethical concerns and biological issues. Conclusions: Traditional and innovative in vitro cell culture systems represent a valid alternative to in vivo animal models in the investigation of the complex mechanisms involved in fibrosis development and in the discovery of new anti-fibrogenic compounds for the treatment of hepatic fibrosis.