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Review
. 2021 May 1;37(3):224-230.
doi: 10.1097/MOG.0000000000000726.

Synthetic human livers for modeling metabolic diseases

Edgar N Tafaleng  1 , Michelle R Malizio  2 , Ira J Fox  1   3   4 , Alejandro Soto-Gutierrez  2   3   4
Affiliations
Review

Synthetic human livers for modeling metabolic diseases

Edgar N Tafaleng et al. Curr Opin Gastroenterol. .

Abstract

Purpose of review: In this review, we will explore recent advances in human induced pluripotent stem cell (iPSC)-based modeling of metabolic liver disease and biofabrication of synthetic human liver tissue while also discussing the emerging concept of synthetic biology to generate more physiologically relevant liver disease models.

Recent finding: iPSC-based platforms have facilitated the study of underlying cellular mechanisms and potential therapeutic strategies for a number of metabolic liver diseases. Concurrently, rapid progress in biofabrication and gene editing technologies have led to the generation of human hepatic tissue that more closely mimic the complexity of the liver.

Summary: iPSC-based liver tissue is rapidly becoming available for modeling liver physiology due to its ability to recapitulate the complex three-dimensional architecture of the liver and recapitulate interactions between the different cell types and their surroundings. These mini livers have also been used to recapitulate liver disease pathways using the tools of synthetic biology, such as gene editing, to control gene circuits. Further development in this field will undoubtedly bolster future investigations not only in disease modeling and basic research, but also in personalized medicine and autologous transplantation.

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Conflict of interest statement

Conflicts of interest

A.S.-G. is inventor on a patent application that involves perfusion technology for organs (WO/2011/002926); A.S.-G. has international patent applications related to this work that describes methods of preparing artificial organs and related compositions for transplantation and regeneration (WO/2015/168254) and (A.S.-G and I.J.F.) hepatic differentiation of human pluripotent stem cells and liver repopulation (PCT/US2018/018032). A.S.-G. 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 Pittsburgh ReLiver Inc. a company focused on programming liver failure and their interests are managed by the Conflict-of-Interest Office at the University of Pittsburgh in accordance with their policies.

Figures

FIGURE 1.
FIGURE 1.
Biofabricated liver tissue and organoids derived from human induced pluripotent stem cells are novel tools that recapitulate key components of human liver structure and function. Utilization of clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 technology and gRNA libraries allows for genetic correction or screening of mutations in these tissue or organoid cells. Deep sequencing of their genomes using NGS may systematically identify potential therapeutic targets or genetic modifiers that can be used to improve clinical trial designs. Future clinical trials can use these genetically modified induced pluripotent stem cell-mini livers to improve precision medicine and treat specific patient populations. gRNA, guide RNA; NGS, next-generation sequencing.
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References

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