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

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Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests H.Y. and A.S.-Gare inventors on a patent application that involves some of the perfusion technology used in this work (WO/2011/002926); K.H., K.M., J.G.-L., H.Y., and A.S.-G. have an international patent related to this work that describes methods of preparing artificial organs and related compositions for transplantation and regeneration (WO/2015/168254). K.T., A.C.H., J.G.-L., Y.W., T.M., and A.S.-G. have a provisional international patent application that describes hepatic differentiation of human pluripotent stem cells and liver repopulation (PCT/US2018/018032). A.S.-G., J.G.-L., K.T., A.C.H., Y.W., T.M., and I.J.F. are co-founders and have a financial interest in Von Baer Wolff, Inc. a company focused on biofabrication of autologous human hepatocytes from stem cells technology and programming liver failure and their interests are managed by the Conflict of Interest Office at the University of Pittsburgh in accordance with their policies.