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

Kazuki Takeishi, Alexandra Collin de l'Hortet, Yang Wang, Kan Handa, Jorge Guzman-Lepe, Kentaro Matsubara, Kazutoyo Morita, Sae Jang, Nils Haep, Rodrigo M. Florentino, Fangchao Yuan, Ken Fukumitsu, Kimimasa Tobita, Wendell Sun, Jonathan Franks, Evan R. Delgado, Erik M. Shapiro, Nicolas A. Fraunhoffer, Andrew W. Duncan, Hiroshi YagiTomoji Mashimo, Ira J. Fox, Alejandro Soto-Gutierrez

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number107711
JournalCell Reports
Volume31
Issue number9
DOIs
Publication statusPublished - Jun 2 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Takeishi, K., Collin de l'Hortet, A., Wang, Y., Handa, K., Guzman-Lepe, J., Matsubara, K., Morita, K., Jang, S., Haep, N., Florentino, R. M., Yuan, F., Fukumitsu, K., Tobita, K., Sun, W., Franks, J., Delgado, E. R., Shapiro, E. M., Fraunhoffer, N. A., Duncan, A. W., ... Soto-Gutierrez, A. (2020). Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells. Cell Reports, 31(9), [107711]. https://doi.org/10.1016/j.celrep.2020.107711