Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture.
Biliary epithelial cell differentiation of bipotent human liver-derived organoids by 2D and 3D culture.
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DOI：
10.1016/j.bbrep.2023.101432
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发表时间：
2023-03
影响因子：
2.7
通讯作者：
Mizuguchi, Hiroyuki
中科院分区：
文献类型：
--
作者：
Tong, Yanran;Ueyama-Toba, Yukiko;Mizuguchi, Hiroyuki
类器官培养是一种用于在体外产生三维（3D）组织样结构的技术，并且被期望用于各种领域。据报道，来源于人活检的人成人胆管细胞可以在体外扩增为类器官，其表现出干细胞样性质，包括向肝细胞和胆管上皮细胞（BEC）的高增殖能力和分化能力。尽管许多研究已经实现了双能人类肝源性类器官（hLO）向成熟肝细胞的有效分化，但向成熟BEC的分化潜能仍不清楚。在这项研究中，我们试图评估双能hLO的分化潜能，这是从原代（冻存）人肝细胞（PHH），对BEC的表皮生长因子（EGF），白细胞介素-6（IL-6），和牛磺胆酸钠水合物的顺序处理。沿着向双能hLO衍生的BEC（Org-BEC）的分化，观察到BEC标志物的基因表达水平增加和BEC典型的内腔样结构的形成。此外，Org-BEC表现出P-糖蛋白介导的药物转运能力。最后，为了扩大Org-BEC的适用性，我们在二维（2D）培养系统中成功地将双能hLO分化为BEC。我们的研究结果表明，双能hLO确实可以分化成成熟的BEC，这意味着它们具有向肝细胞和BEC分化的能力。建立了双能人类肝脏衍生的类器官（hLO）。双能hLO分化为成熟的胆管细胞。hLO衍生的胆管上皮细胞可以在各种条件下培养。
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. Bipotent human liver-derived organoids (hLOs) were established. Bipotent hLOs differentiated into mature cholangiocytes. hLOs-derived biliary epithelial cells could be cultured under various conditions.
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影响因子：
13.5
作者：
Dianat, Noushin;Dubois-Pot-Schneider, Helene;Steichen, Clara;Desterke, Christophe;Leclerc, Philippe;Raveux, Aurelien;Combettes, Laurent;Weber, Anne;Corlu, Anne;Dubart-Kupperschmitt, Anne
通讯作者：
Dubart-Kupperschmitt, Anne
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.8
作者：
Sampaziotis F;de Brito MC;Geti I;Bertero A;Hannan NR;Vallier L
通讯作者：
Vallier L
影响因子：
64.5
作者：
Huch M;Gehart H;van Boxtel R;Hamer K;Blokzijl F;Verstegen MM;Ellis E;van Wenum M;Fuchs SA;de Ligt J;van de Wetering M;Sasaki N;Boers SJ;Kemperman H;de Jonge J;Ijzermans JN;Nieuwenhuis EE;Hoekstra R;Strom S;Vries RR;van der Laan LJ;Cuppen E;Clevers H
通讯作者：
Clevers H
DOI：
10.1002/ar.20664
发表时间：
2008-06-01
影响因子：
2
作者：
Strazzabosco, Mario;Fabris, Luca
通讯作者：
Fabris, Luca