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

• DOI: 10.1016/j.celrep.2020.107711
• Publication Date: 2020-06-02T14:37:38Z
• Authors: Kazuki Takeishi; Alexandra Collin ...; Yang Wang; Kan Handa; Jorge Guzman-Lepe; Kentaro Matsubara; Kazutoyo Morita; Sae Jang; Nils Haep; Rodrigo M. Floren...; Fangchao Yuan; Ken Fukumitsu; Kimimasa Tobita; Wendell Sun; Jonathan Franks; Evan R. Delgado; Erik M. Shapiro; Nicolas A. Fraunh...; Andrew W. Duncan; Hiroshi Yagi; Tomoji Mashimo; Ira J. Fox; Alejandro Soto-Gu...
• Keywords: Male; QH301-705.5; Induced Pluripotent Stem Cells; Bone Morphogenetic Protein 4; human iPS-biliary cells; human iPS cells; human iPS-endothelial cells; Rats, Sprague-Dawley; Immunocompromised Host; Fetus; https://purl.org/becyt/ford/3.1; Animals; Humans; https://purl.org/becyt/ford/3; Biology (General); Cells, Cultured; HUMAN IPS-ENDOTHELIAL CELLS; HUMAN IPS-HEPATOCYTES; LIVER MATURATION; Tissue Engineering; Tissue Scaffolds; TRANSPLANTATION; MINI HUMAN LIVER; Cell Differentiation; Fibroblasts; Cellular Reprogramming; Activins; Rats; 3. Good health; bioengineered human liver; Hepatocytes; HUMAN IPS-BILIARY CELLS; Fibroblast Growth Factor 2; human iPS-hepatocytes; BIOENGINEERED HUMAN LIVER; HUMAN IPS CELLS; ORGAN-MICROENVIRONMENT; transplantation; Transcription Factors

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.