Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
By Meritxell Huch, H. Gehart, R. van Boxtel, K. Hamer, Francis Blokzijl, M. Verstegen, E. Ellis, M. van Wenum, S. Fuchs, J. de Ligt and 13 more. Cell, 2015
1,446 citations recorded by the source corpus.
Summary 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.
Subfields: Hepatology, Surgery
View Paper: https://www.semanticscholar.org/paper/858b0e63b2d3f25f16595d13280945153f895c29
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Citations in the corpus
- Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids. (2018, neutral): “We have recently described a long-term 3D liver expansion system of mouse and human adult biliary epithelial-derived progenitor cells that mirrors the in vivo oval cell response (Huch et al., 2013; Huch et al., 2015).”
- Tissue-specific mutation accumulation in human adult stem cells during life (2016, neutral): “Here, we experimentally define ASCs as those cells that give rise to long-term organoid cultures and have the potential to differentiate into multiple tissue-specific cell types 3–5 .”
- Long‐term expanding human airway organoids for disease modeling (2019, neutral): “…experience with generating organoids from other adult human tissues (Sato et al , 2011; Karthaus et al , 2014; Boj et al , 2015; Huch et al , 2015; van de Wetering et al , 2015) and recent developments in the field (Mou et al , 2016; Tadokoro et al , 2016; Balasooriya et al , 2017), we embedded…”
- Modeling Development and Disease with Organoids. (2016, background): “Again, the cells could be converted into functional hepatocytes in vitro and upon transplantation into mice (Huch et al., 2015).”