Engineering the Liver Diverticulum from Human Pluripotent Stem Cells

摘要

Liver tissue demand is escalating due to the greatly increasing incidence of liver disease.We hypothesize that the structures and cues that initiate 3D liver formation can be mimicked with human pluripotent stem cells(hPSC).Thus we aimed to engineer an in vitro model of the liver diverticulum(LD),a key structure that: 1)arises in mouse development(E9.5)and human development(d26)and 2)forms the 3D liver.From inside the gut to outside,the LD is composed of a single layer of hepatic endoderm(HE),encased by a single layer of endothelial cells,and surrounded by the septum transversum mesenchyme(STM).3D liver formation starts when the hepatic endoderm(HE)delaminates,joins with the endothelial cells,and migrates into the STM.We first determined the appropriate LD dimensions with an online mouse database.Next,to model the LD,we used a commercially available cell migration system,which enabled selective cell seeding and cell adhesion of two migrating cell types,on 0.22 cm2 square islands separated by 500 I1/4m.