Expansion of human primary hepatocytes in vitro through their amplification as liver progenitors in a 3D organoid system

Scientific Reports
Delphine GarnierTuan Huy Nguyen

Abstract

Despite decades of investigation on the proliferation of adult human primary hepatocytes, their expansion in vitro still remains challenging. To later be able to consider hepatocytes as a cell therapy alternative or bridge to liver transplantation, dramatically impeded by a shortage in liver donors, the first step is having an almost unlimited source of these cells. The banking of transplantable hepatocytes also implies a protocol for their expansion that can be compatible with large-scale production. We show that adult human primary hepatocytes when grown in 3D organoids are easily amplified, providing a substantial source of functional hepatocytes ready for transplantation. Following their plating, differentiated human hepatocytes are amplified during a transient and reversible step as liver progenitors, and can subsequently be converted back to mature differentiated hepatocytes. The protocol we propose is not only compatible with automated and high-throughput cell culture systems, thanks to the expansion of hepatocytes in suspension, but also guarantees the generation of a high number of functional cells from the same patient sample, with a relatively easy set up.

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Citations

Jul 25, 2018·Journal of Thrombosis and Haemostasis : JTH·C Espitia JaimesM Neerman-Arbez
Nov 13, 2018·Personalized Medicine·Lukas PerkhoferAlexander Kleger
May 14, 2019·Journal of Cellular Biochemistry·Zahra FeiziMassoud Vosough
Apr 17, 2019·Tissue Engineering and Regenerative Medicine·Jie WangMiao Li
Apr 15, 2020·Annals of Biomedical Engineering·Katya D'CostaMilica Radisic
May 28, 2020·International Journal of Molecular Sciences·Marie-Noëlle LabourDidier Letourneur
Jan 5, 2021·Advanced Functional Materials·Dantong HuangKam W Leong
Apr 29, 2021·Biological Chemistry·Linda Große-Segerath, Eckhard Lammert
Feb 28, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Junya ShiotaNataliya Razumilava

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Methods Mentioned

BETA
FACS
phase contrast

Software Mentioned

GraphPad Prism

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