Large-Scale Production of LGR5-Positive Bipotential Human Liver Stem Cells.
Hepatology
; 72(1): 257-270, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-31715015
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 ANDRESULTS:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Organoides
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Transplante de Fígado
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Técnicas de Cultura de Células
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Hepatócitos
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Engenharia Tecidual
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Receptores Acoplados a Proteínas G
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Proliferação de Células
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Regeneração Hepática
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article