Scalable production oftissue-like vascularised liver organoids from human PSCs.
Organoid models have been developed for a number of tissues including the liver. Currenthepatic organoid models are generally simplistic, composed of hepatocytes orcholangiocytes, rendering them less physiologically relevant when compared to nativetissue. To address this we have developed an approach that does not require 2Dpatterning, which is ECM independent and growth factor free, to mimic embryonic liverdevelopment that produces massive quantities of liver like organoids. Using single-cell RNAsequencing and immunofluorescence we demonstrate a liver-like cellular repertoire,presenting with vascular luminal structures,and a population of resident macrophage – theKupffer cells. The organoids exhibit key liver functions including drug metabolism, serumprotein production, urea synthesis and coagulation factor production, which preservedpost-translational modifications such as N-glycosylation and functionality. The organoidscan be transplanted and maintained inmice producing human albumin long term.Theorganoids exhibit a complex cellular repertoire reflective of the organ, havede novovascularization, and liver like function. This isa pre-requisite for a myriad of applicationsfrom cellular therapy, tissue engineering, drug toxicity assessment, disease modeling, tobasic developmental biology. Overall design: Liver organoids differentiated from human pluripotent stem cells