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. BaptistaBart Spee

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

60 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)257-270
Aantal pagina's14
TijdschriftHepatology
Volume72
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 1 jul. 2020

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