Abstract
Simple SummaryLiver organoids represent a breakthrough for disease modeling as proven by their ability to recapitulate pathophysiological morphology and functional features of the original tissue. This article reviews the works that established liver organoids and the recent improvements of this novel in vitro system. We discuss their application in biomedicine focusing on disease modeling, regenerative medicine and drug discovery.Liver organoids are stem cell-derived 3D structures that are generated by liver differentiation signals in the presence of a supporting extracellular matrix. Liver organoids overcome low complexity grade of bidimensional culture and high costs of in vivo models thus representing a turning point for studying liver disease modeling. Liver organoids can be established from different sources as induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), hepatoblasts and tissue-derived cells. This novel in vitro system represents an innovative tool to deeper understand the physiology and pathological mechanisms affecting the liver. In this review, we discuss the current advances in the field focusing on their application in modeling diseases, regenerative medicine and drug discovery.
Highlights
These hepatic organoids contain 2 types of cells organized into a complex structure: sheets of hepatocytes and the cholangiocytes are organized into epithelia surrounding the lumina of bile duct–like structures
Patient derived xenografts (PDX), in which cells from patients are transplanted in immunocompromised mice, are more suitable for Primary liver cancer (PLC) studies as they recapitulate the features of the original tumors
Liver organoids models have increasingly been incorporated in biomedical research as they present many advantages
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Due to the lack of cell-cell communication and tissue microenvironment, bi-dimensional (2D) cultures do not faithfully represent complete and accurate physiological and pathological features [1]. For this reason, since the 70’s, the development of three-dimensional (3D) cultures has been implemented [2,3]. Several groups established 3D structures, defined organoids, obtained by culturing stem cells with an extracellular matrix (ECM), allowing a self-organization in a structure resembling structural and functional parameters of the tissue of interest [4,5]. LGR5positive (LGR5+) stem cells have been isolated from many other organs enlightening the pivotal role of Wnt signaling in the maintenance of the stemness [8]
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