A fully defined matrix to support a pluripotent stem cell derived multi-cell-liver steatohepatitis and fibrosis model

Chronic liver injury, as observed in non-alcoholic steatohepatitis (NASH), progressive fibrosis, and cirrhosis, remains poorly treatable. Steatohepatitis causes hepatocyte loss part by a direct lipotoxic insult, which is amplified derangements the non-parenchymal cellular (NPC) interactive network wherein hepatocytes reside, including, hepatic stellate cells, sinusoidal endothelial cells macrophages. To create an vitro culture model encompassing all these that allows studying steatosis, inflammation fibrosis caused NASH, we here developed fully defined hydrogel microenvironment, termed maturation (HepMat) gel, supports maintenance of pluripotent stem cell (PSC) derived hepatocyte- NPC-like for at least one month. The HepMat-based co-culture system modeled key molecular functional features TGF?-induced fatty-acid induced better than monocultures its constituent populations. novel should open new avenues mechanisms underlying well assessing drugs counteracting effects.