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CC BY-NC-ND 4.0 · Semin Liver Dis 2022; 42(04): 413-422
DOI: 10.1055/a-1934-5404
Review Article

From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation

Takashi Motomura‡   *
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Lanuza A.P. Faccioli‡   *
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Ricardo Diaz-Aragon
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Zehra N. Kocas-Kilicarslan
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Nils Haep
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Rodrigo M. Florentino
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Sriram Amirneni
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Zeliha Cetin
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Bhaavna S. Peri
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Kazutoyo Morita
2   Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
,
Alina Ostrowska
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
3   Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Kazuki Takeishi
2   Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
,
Alejandro Soto-Gutierrez‡   #
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
3   Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
4   McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania
,
Edgar N. Tafaleng‡   #
1   Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Abstract

Although the underlying cause may vary across countries and demographic groups, liver disease is a major cause of morbidity and mortality globally. Orthotopic liver transplantation is the only definitive treatment for liver failure but is limited by the lack of donor livers. The development of drugs that prevent the progression of liver disease and the generation of alternative liver constructs for transplantation could help alleviate the burden of liver disease. Bioengineered livers containing human induced pluripotent stem cell (iPSC)–derived liver cells are being utilized to study liver disease and to identify and test potential therapeutics. Moreover, bioengineered livers containing pig hepatocytes and endothelial cells have been shown to function and survive after transplantation into pig models of liver failure, providing preclinical evidence toward future clinical applications. Finally, bioengineered livers containing human iPSC-derived liver cells have been shown to function and survive after transplantation in rodents but require considerable optimization and testing prior to clinical use. In conclusion, bioengineered livers have emerged as a suitable tool for modeling liver diseases and as a promising alternative graft for clinical transplantation. The integration of novel technologies and techniques for the assembly and analysis of bioengineered livers will undoubtedly expand future applications in basic research and clinical transplantation.

Keywords

bioengineered liver - disease modeling - transplantation - liver disease - induced pluripotent stem cells

Financial Support

This work was supported by NIH grants DK099257, DK119973, TR003289, TR002383, DK120531 and DK096990 to A.S.-G.. Funding received from U.S. Department of Health and Human Services, National Institutes of Health, National Center for Advancing Translational Sciences (002383, 003289); U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (096990, 099257, 119973, 120531).


* These authors contributed equally to this work and share first authorship.


# These authors contributed equally to this work and share the last authorship.




Publication History

Accepted Manuscript online:
31 August 2022

Article published online:
19 October 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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