Organoids to model liver disease

Abstract

The organoid model represents a major breakthrough in cell biology that has revolutionised biomedical research. Organoids are 3D physiological in vitro structures that recapitulate morphological and functional features of in vivo tissues and offer significant advantages over traditional cell culture methods. Liver organoids are of particular interest because of the pleiotropy of functions exerted by the human liver, their utility to model different liver diseases, and their potential application as cell-based therapies in regenerative medicine. Moreover, because they can be derived from patient tissues, organoid models offer new perspectives in personalised medicine and drug discovery. In this review, we discuss the current liver organoid models for the study of liver disease.

Keywords: 3D cultures; A1AT, alpha-1 antitrypsin; ALD, alcohol-related liver disease; CCA, cholangiocarcinoma; CFTR, cystic fibrosis transmembrane conductance regulator; CHC, combined hepato-cholangiocarcinoma; CLD, chronic liver disease; CTLN1, citrullinemia type 1; Chol-orgs, cholangiocyte organoids; Disease modelling; EGF, epidermal growth factor; ER, endoplasmic reticulum; ESCs, embryonic stem cells; FFAs, free fatty acids; HCC, hepatocellular carcinoma; HUVEC, human umbilical vein endothelial cells; Hep-orgs, hepatocyte organoids; IL-, interleukin-; Liver disease; MSC, mesenchymal stem cell; NAFLD, non-alcoholic fatty liver disease; Organoids; PDO, patient-derived organoid; PDX, patient-derived xenograft; PHH, primary human hepatocyte; PSC, primary sclerosing cholangitis; Personalised medicine; Preclinical models; iPSC, induced pluripotent stem cell.