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Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Despite 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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313365/ https://www.ncbi.nlm.nih.gov/pubmed/25533785 http://dx.doi.org/10.1016/j.cell.2014.11.050 |
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author | 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 |
author_facet | 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 |
author_sort | Huch, Meritxell |
collection | PubMed |
description | Despite 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. |
format | Online Article Text |
id | pubmed-4313365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43133652015-02-09 Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver 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 Cell Article Despite 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. Cell Press 2015-01-15 /pmc/articles/PMC4313365/ /pubmed/25533785 http://dx.doi.org/10.1016/j.cell.2014.11.050 Text en © 2015 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article 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 Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver |
title | Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver |
title_full | Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver |
title_fullStr | Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver |
title_full_unstemmed | Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver |
title_short | Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver |
title_sort | long-term culture of genome-stable bipotent stem cells from adult human liver |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313365/ https://www.ncbi.nlm.nih.gov/pubmed/25533785 http://dx.doi.org/10.1016/j.cell.2014.11.050 |
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