荷兰鹿特丹大学医学中心外科Luc J.W. van der Laan研究组建立了人分支胆管细胞类器官 (BRCO)，并概括了功能性胆管的形成。2022年5月5日出版的《细胞—干细胞》杂志发表了这项成果。

他们报告了建立BRCO培养物。BRCO 自组织成类似于肝内胆管 (IHBD)架构的复杂管状结构。单细胞转录组学和功能分析显示与原代胆管细胞高度相似，重要的是，分支生长模拟了肾小管发育的各个方面，并且依赖于 JAG1/NOTCH2 信号传导。当应用于胆管癌肿瘤类器官时，形态会变为体外形态，如原发性肿瘤。

此外，这些分支胆管癌类器官 (BRCCAO) 更好地匹配原发性肿瘤的转录组学特征，并显示出对吉西他滨和顺铂的化学抗性增加。总之，BRCO 概括了体外分支形态发生的复杂过程。这为研究肾小管形成、胆管功能和相关胆道疾病提供了一个改进的模型。

研究人员表示，人类胆管细胞类器官在再生疗法和胆管发育和疾病的体外建模方面显示出巨大的前景。然而，囊性类器官缺乏IHBD的分支形态。

附：英文原文

Title: Human branching cholangiocyte organoids recapitulate functional bile duct formation

Author: Floris J.M. Roos, Gilles S. van Tienderen, Haoyu Wu, Ignacio Bordeu, Dina Vinke, Laura Muoz Albarinos, Kathryn Monfils, Sabrah Niesten, Ron Smits, Jorke Willemse, Oskar Rosmark, Gunilla Westergren-Thorsson, Daniel J. Kunz, Maurice de Wit, Pim J. French, Ludovic Vallier, Jan N.M. IJzermans, Richard Bartfai, Hendrik Marks, Ben D. Simons, Martin E. van Royen, Monique M.A. Verstegen, Luc J.W. van der Laan

Issue&Volume: 2022/05/05

Abstract: Human cholangiocyte organoids show great promise for regenerative therapies and in vitro modeling of bile duct development and diseases. However, the cystic organoids lackthe branching morphology of intrahepatic bile ducts (IHBDs). Here, we report establishinghuman branching cholangiocyte organoid (BRCO) cultures. BRCOs self-organize into complextubular structures resembling the IHBD architecture. Single-cell transcriptomics andfunctional analysis showed high similarity to primary cholangiocytes, and importantly,the branching growth mimics aspects of tubular development and is dependent on JAG1/NOTCH2signaling. When applied to cholangiocarcinoma tumor organoids, the morphology changesto an in vitro morphology like primary tumors. Moreover, these branching cholangiocarcinoma organoids (BRCCAOs) better match thetranscriptomic profile of primary tumors and showed increased chemoresistance to gemcitabineand cisplatin. In conclusion, BRCOs recapitulate a complex process of branching morphogenesisin vitro. This provides an improved model to study tubular formation, bile duct functionality, and associated biliary diseases.

DOI: 10.1016/j.stem.2022.04.011

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00164-3