Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Human iPSC-Derived 3D Hepatic Organoids in a Miniaturized Dynamic Culture System

Serena Calamaio
ORCID logo ,
Marialaura Serzanti
,
Jennifer Boniotti
,
Annamaria Fra
ORCID logo ,
Emirena Garrafa
,
Manuela Cominelli
,
Rosanna Verardi
,
Pietro Luigi Poliani
ORCID logo ,
Silvia Dotti
ORCID logo ,
Riccardo Villa
ORCID logo ,
Giovanna Mazzoleni
,
Patrizia Dell'Era
* ORCID logo ,
Nathalie Steimberg
* ORCID logo
Version 1 : Received: 23 June 2023 / Approved: 25 June 2023 / Online: 25 June 2023 (05:08:36 CEST)

A peer-reviewed article of this Preprint also exists.

Calamaio, S.; Serzanti, M.; Boniotti, J.; Fra, A.; Garrafa, E.; Cominelli, M.; Verardi, R.; Poliani, P.L.; Dotti, S.; Villa, R.; Mazzoleni, G.; Dell’Era, P.; Steimberg, N. Human iPSC-Derived 3D Hepatic Organoids in a Miniaturized Dynamic Culture System. Biomedicines 2023, 11, 2114. Calamaio, S.; Serzanti, M.; Boniotti, J.; Fra, A.; Garrafa, E.; Cominelli, M.; Verardi, R.; Poliani, P.L.; Dotti, S.; Villa, R.; Mazzoleni, G.; Dell’Era, P.; Steimberg, N. Human iPSC-Derived 3D Hepatic Organoids in a Miniaturized Dynamic Culture System. Biomedicines 2023, 11, 2114.

Abstract

The process of identifying and approving a new drug is a time-consuming and expensive procedure. One of the biggest issues to overcome is the risk of hepatotoxicity, which is one of the main reasons for drug withdrawal from the market. While animal models are the gold standard in preclinical drug testing, the translation of results into therapeutic intervention is often ambiguous due to interspecies differences in hepatic metabolism. The discovery of human induced Pluripotent Stem Cells (hiPSCs) and their derivatives has opened new possibilities for drug testing. We used mesenchymal stem cells and hepatocytes both derived from hiPSC, together with endothelial cells, to miniaturize the process of generating hepatic organoids. These organoids were then cultivated in vitro using both static and dynamic cultures. Additionally, we tested spheroids composed solely by induced hepatocytes. By miniaturizing the system, we demonstrated the possibility of maintaining the organoids, but not the spheroids, in culture for up to 15 days. This timeframe may be sufficient to carry out a hypothetical pharmacological test or screening. In conclusion, we propose that the hiPSC-derived liver organoids model could complement or, in the near future, replace the pharmacological and toxicological tests conducted on animals.

Keywords

liver; hiPSC; organoids; 3D dynamic culture; organotypic culture

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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