Large-scale production of LGR5-positive bipotential human liver stem cells
Schneeberger, K. ; Sánchez-Romero, N. ; Ye, S.C. ; van Steenbeek, F.G. ; Oosterhoff, L.A. ; Pla Palacin, I. ; Chen, C. ; van Wolferen, M.E. ; van Tienderen, G. ; Lieshout, R. ; Colemonts-Vroninks, H. ; Schene, I. ; Hoekstra, R. ; Verstegen, M.M.A. ; van der Laan, L.J.W. ; Penning, L.C. ; Fuchs, S.A. ; Clevers, H. ; De Kock, J. ; Baptista, P.M. ; Spee, B.
Resumen: 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.
Idioma: Inglés
DOI: 10.1002/hep.31037
Año: 2020
Publicado en: HEPATOLOGY 72, 1 (2020), 257-270
ISSN: 0270-9139
Factor impacto JCR: 17.425 (2020)
Categ. JCR: GASTROENTEROLOGY & HEPATOLOGY rank: 6 / 92 = 0.065 (2020) - Q1 - T1
Factor impacto SCIMAGO: 5.488 - Medicine (miscellaneous) (Q1) - Hepatology (Q1)
Financiación: info:eu-repo/grantAgreement/EC/H2020/874586/EU/Organ 3D printing for liver regenerative medicine/ORGANTRANS
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI15-00563
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI18-00529
Tipo y forma: Article (Published version)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original.
Exportado de SIDERAL (2021-09-02-08:56:05)
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Idioma: Inglés
DOI: 10.1002/hep.31037
Año: 2020
Publicado en: HEPATOLOGY 72, 1 (2020), 257-270
ISSN: 0270-9139
Factor impacto JCR: 17.425 (2020)
Categ. JCR: GASTROENTEROLOGY & HEPATOLOGY rank: 6 / 92 = 0.065 (2020) - Q1 - T1
Factor impacto SCIMAGO: 5.488 - Medicine (miscellaneous) (Q1) - Hepatology (Q1)
Financiación: info:eu-repo/grantAgreement/EC/H2020/874586/EU/Organ 3D printing for liver regenerative medicine/ORGANTRANS
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI15-00563
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI18-00529
Tipo y forma: Article (Published version)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original. Exportado de SIDERAL (2021-09-02-08:56:05)
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Record created 2020-06-09, last modified 2021-09-02