Long-term culture of genome-stable bipotent stem cells from adult human liver
| Autor: | Huch, Meritxell, Gehart, Helmuth, van Boxtel, Ruben, Hamer, Karien, Blokzijl, Francis, Verstegen, Monique M. A., Ellis, Ewa, van Wenum, Martien, Fuchs, Sabine A., de Ligt, Joep, van de Wetering, Marc, Sasaki, Nobuo, Boers, Susanne J., Kemperman, Hans, de Jonge, Jeroen, Ijzermans, Jan N. M., Nieuwenhuis, Edward E. S., Hoekstra, Ruurdtje, Strom, Stephen, Vries, Robert R. G., van der Laan, Luc J. W., Cuppen, Edwin, Clevers, Hans |
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| Přispěvatelé: | Huch Ortega, Meritxell [0000-0002-1545-5265], Apollo - University of Cambridge Repository, Hubrecht Institute for Developmental Biology and Stem Cell Research, Surgery, Graduate School, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
IN-VITRO EXPANSION
IDENTIFICATION Biochemistry Genetics and Molecular Biology(all) MOUSE MODEL HEPATOCYTES ALPHA-1-ANTITRYPSIN DEFICIENCY Genomic Instability Organoids Mice COPY NUMBER LGR5 DIFFERENTIATION Organ Culture Techniques SDG 3 - Good Health and Well-being Liver REGENERATION Hepatocytes Animals Humans ALAGILLE-SYNDROME |
| Zdroj: | Cell, 160(1-2), 299-312. Elsevier B.V. CELL Cell, 160(1-2), 299-312. Cell Press Cell, 160(1-2), 299. Cell Press |
| ISSN: | 0092-8674 |
| Popis: | SummaryDespite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. |
| Databáze: | OpenAIRE |
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