Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells

The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg−/−) rats. [Display omitted] •Organ-like microenvironment further matures human iPSC mini livers•Human vascular and biliary network can be engineered in decellularized liver scaffolds•Human iPSC-mini-liver microstructure has similarities to human liver•Human iPSC-derived mini livers can be transplanted in immunodeficient rats Takeishi et al. biofabricate human livers for transplantation using human hepatocytes, biliary epithelial cells, and vascular endothelial cells. All originate from induced pluripotent stem cells, human mesenchymal cells, and fibroblasts. The organ-like microenvironment further matures some liver functions and produces tissue structures similar to those found in human livers.