Large‐scale Production of LGR5‐positive Bipotential Human Liver Stem Cells

Kerstin Schneeberger, Natalia Sánchez‐Romero , Shicheng Ye, Frank G van Steenbeek, Loes A Oosterhoff, Iris Pla Palacin , Chen Chen, Monique E. van Wolferen , Gilles van Tienderen , Ruby Lieshout, Haaike Colemonts-Vroninks, Imre Schene, Ruurdtje Hoekstra, Monique M.A. Verstegen , Luc J.W. van der Laan , Louis C. Penning , Sabine A. Fuchs , Hans Clevers, Joery De Kock, Pedro M. Baptista Bart Spee

Research output: Contribution to journalArticle

7 Citations (Scopus)
1 Downloads (Pure)

Abstract

Background and Aims: The gap between patients on transplant waiting lists and available donor organs is steadily increasing. Human organoids derived from leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)–positive adult stem cells represent an exciting new cell source for liver regeneration; however, culturing large numbers of organoids with current protocols is tedious and the level of hepatic differentiation is limited. Approach and Results: Here, we established a method for the expansion of large quantities of human liver organoids in spinner flasks. Due to improved oxygenation in the spinner flasks, organoids rapidly proliferated and reached an average 40-fold cell expansion after 2 weeks, compared with 6-fold expansion in static cultures. The organoids repopulated decellularized liver discs and formed liver-like tissue. After differentiation in spinner flasks, mature hepatocyte markers were highly up-regulated compared with static organoid cultures, and cytochrome p450 activity reached levels equivalent to hepatocytes. Conclusions: We established a highly efficient method for culturing large numbers of LGR5-positive stem cells in the form of organoids, which paves the way for the application of organoids for tissue engineering and liver transplantation.

Original languageEnglish
Pages (from-to)257-270
Number of pages14
JournalHepatology
Volume72
Issue number1
DOIs
Publication statusPublished - 1 Jul 2020

Bibliographical note

© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.

Fingerprint Dive into the research topics of 'Large‐scale Production of LGR5‐positive Bipotential Human Liver Stem Cells'. Together they form a unique fingerprint.

Cite this