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

Takashi Motomura; Lanuza A.P. Faccioli; Ricardo Diaz-Aragon; Zehra N. Kocas-Kilicarslan; Nils Haep; Rodrigo M. Florentino; Sriram Amirneni; Zeliha Cetin; Bhaavna S. Peri; Kazutoyo Morita; Alina Ostrowska; Kazuki Takeishi; Alejandro Soto-Gutierrez; Edgar N. Tafaleng

doi:10.1055/a-1934-5404

Seminars in Liver Disease, Table of Contents

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

Authors

Takashi Motomura‡^*

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Lanuza A.P. Faccioli‡^*

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Ricardo Diaz-Aragon

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Zehra N. Kocas-Kilicarslan

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Nils Haep

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Rodrigo M. Florentino

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Sriram Amirneni

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Zeliha Cetin

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Bhaavna S. Peri

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Kazutoyo Morita

²Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Alina Ostrowska

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

³Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Kazuki Takeishi

²Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Alejandro Soto-Gutierrez‡^#

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

³Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

⁴McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania
Edgar N. Tafaleng‡^#

¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

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

Full Text

References

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