| Literature DB >> 32492423 |
Kazuki Takeishi1, Alexandra Collin de l'Hortet2, Yang Wang3, Kan Handa2, Jorge Guzman-Lepe2, Kentaro Matsubara2, Kazutoyo Morita2, Sae Jang2, Nils Haep2, Rodrigo M Florentino4, Fangchao Yuan5, Ken Fukumitsu2, Kimimasa Tobita6, Wendell Sun7, Jonathan Franks8, Evan R Delgado9, Erik M Shapiro10, Nicolas A Fraunhoffer11, Andrew W Duncan9, Hiroshi Yagi12, Tomoji Mashimo13, Ira J Fox14, Alejandro Soto-Gutierrez15.
Abstract
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.Entities:
Keywords: bioengineered human liver; human iPS cells; human iPS-biliary cells; human iPS-endothelial cells; human iPS-hepatocytes; liver maturation; mini human liver; organ-microenvironment; transplantation
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Year: 2020 PMID： 32492423 PMCID： PMC7734598 DOI： 10.1016/j.celrep.2020.107711
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423