Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture
Organoid culture is a technology for creating three-dimensional (3D) tissue-like structures in vitro, and is expected to be used in various fields. It was reported that human adult bile duct cells derived from human biopsy can be expanded as organoids in vitro that exhibit stem cell-like properties...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580823000134 |
| _version_ | 1811167231335202816 |
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| author | Yanran Tong Yukiko Ueyama-Toba Hiroyuki Mizuguchi |
| author_facet | Yanran Tong Yukiko Ueyama-Toba Hiroyuki Mizuguchi |
| author_sort | Yanran Tong |
| collection | DOAJ |
| description | Organoid culture is a technology for creating three-dimensional (3D) tissue-like structures in vitro, and is expected to be used in various fields. It was reported that human adult bile duct cells derived from human biopsy can be expanded as organoids in vitro that exhibit stem cell-like properties including high proliferative ability and differentiation ability toward both hepatocytes and biliary epithelial cells (BECs). Although many studies have achieved the efficient differentiation of bipotent human liver-derived organoids (hLOs) toward mature hepatocytes, the differentiation potency toward mature BECs remains unclear. In this study, we attempted to evaluate the differentiation potency of bipotent hLOs, which were generated from primary (cryopreserved) human hepatocytes (PHHs), toward BECs by sequential treatment with epidermal growth factor (EGF), Interleukin-6 (IL-6), and sodium taurocholate hydrate. Along with the differentiation toward bipotent hLOs-derived BECs (Org-BECs), increases in the gene expression levels of BEC markers and formation of the lumen-like structures typical of BECs were observed. In addition, Org-BECs exhibited P-glycoprotein-mediated drug transport capacity. Finally, in order to expand the applicability of Org-BECs, we succeeded in the differentiation of bipotent hLOs toward BECs in a two-dimensional (2D) culture system. Our findings demonstrated that bipotent hLOs can indeed differentiate into mature BECs, meaning that they possess a capacity for differentiation toward both hepatocytes and BECs. |
| first_indexed | 2024-04-10T16:06:56Z |
| format | Article |
| id | doaj.art-49457e9253c3460b8b3fa4cb6265086b |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-04-10T16:06:56Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-49457e9253c3460b8b3fa4cb6265086b2023-02-10T04:22:51ZengElsevierBiochemistry and Biophysics Reports2405-58082023-03-0133101432Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D cultureYanran Tong0Yukiko Ueyama-Toba1Hiroyuki Mizuguchi2Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Functional Organoid for Drug Discovery, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, 565-0871, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Functional Organoid for Drug Discovery, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Osaka, 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, 565-0871, Japan; Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, 565-0871, Japan; Corresponding author. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1–6 Yamadaoka, Suita, Osaka, 565–0871, Japan.Organoid culture is a technology for creating three-dimensional (3D) tissue-like structures in vitro, and is expected to be used in various fields. It was reported that human adult bile duct cells derived from human biopsy can be expanded as organoids in vitro that exhibit stem cell-like properties including high proliferative ability and differentiation ability toward both hepatocytes and biliary epithelial cells (BECs). Although many studies have achieved the efficient differentiation of bipotent human liver-derived organoids (hLOs) toward mature hepatocytes, the differentiation potency toward mature BECs remains unclear. In this study, we attempted to evaluate the differentiation potency of bipotent hLOs, which were generated from primary (cryopreserved) human hepatocytes (PHHs), toward BECs by sequential treatment with epidermal growth factor (EGF), Interleukin-6 (IL-6), and sodium taurocholate hydrate. Along with the differentiation toward bipotent hLOs-derived BECs (Org-BECs), increases in the gene expression levels of BEC markers and formation of the lumen-like structures typical of BECs were observed. In addition, Org-BECs exhibited P-glycoprotein-mediated drug transport capacity. Finally, in order to expand the applicability of Org-BECs, we succeeded in the differentiation of bipotent hLOs toward BECs in a two-dimensional (2D) culture system. Our findings demonstrated that bipotent hLOs can indeed differentiate into mature BECs, meaning that they possess a capacity for differentiation toward both hepatocytes and BECs.http://www.sciencedirect.com/science/article/pii/S2405580823000134LiverBipotent organoidsBiliary epithelial cellsDifferentiation |
| spellingShingle | Yanran Tong Yukiko Ueyama-Toba Hiroyuki Mizuguchi Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture Biochemistry and Biophysics Reports Liver Bipotent organoids Biliary epithelial cells Differentiation |
| title | Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture |
| title_full | Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture |
| title_fullStr | Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture |
| title_full_unstemmed | Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture |
| title_short | Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture |
| title_sort | biliary epithelial cell differentiation of bipotent human liver derived organoids by 2d and 3d culture |
| topic | Liver Bipotent organoids Biliary epithelial cells Differentiation |
| url | http://www.sciencedirect.com/science/article/pii/S2405580823000134 |
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