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胆管类器官的创新构建与应用:揭示胆管疾病的复杂性及潜在治疗策略

Innovative construction and application of bile duct organoids: Unraveling the complexity of bile duct diseases and potential therapeutic strategies.

作者信息

Geng Yadi, Chen Ziye, Luo Tianzi, Liu Yakun, Kong Siming, Yan Xinlong, Bai Hui, Wang Yunfang

机构信息

Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science, Beijing University of Technology, Beijing, 100124, China; School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Hepato-Pancreato-Biliary Center, Tsinghua University, Beijing, 102218, China.

School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Hepato-Pancreato-Biliary Center, Tsinghua University, Beijing, 102218, China.

出版信息

Cancer Lett. 2025 May 28;618:217619. doi: 10.1016/j.canlet.2025.217619. Epub 2025 Mar 10.

Abstract

The biliary system is crucial for liver function, regulating bile production, secretion, and transport. Dysfunctions within this system can lead to various diseases, such as cholangiopathies and biliary fibrosis, which may progress from benign to malignant states like cholangiocarcinoma. While liver organoid research is well-established and technologically advanced, bile duct organoids (BDOs) offer significant potential. BDOs can accurately simulate the physiological structure and function of bile ducts, making them valuable tools for in-vitro biliary disease research. Here, we review the development of BDO models, focusing on stem cell-derived organoids and tissue-derived organoids. We also illustrate the role of cultivation strategies and extracellular scaffolds in supporting organoid growth and stability, including the influence of cellular components of the microenvironment and physicochemical factors. Furthermore, we discuss the applications of BDOs in biliary development, disease modeling, regenerative medicine, and drug screening. Additionally, we emphasize the transformative potential in BDO biobanks and personalized medicine, which helps to pave the way for innovative therapeutic strategies and personalized medicine. Finally, we summarize the current and prospective advancements in BDO technologies, highlighting the integration of emerging technologies such as artificial intelligence, 3D bioprinting, and organoid-on-chip systems. These technologies hold great promise for significantly enhancing both clinical and research applications in the field of biliary diseases.

摘要

胆道系统对肝脏功能至关重要,它调节胆汁的生成、分泌和运输。该系统内的功能障碍可导致多种疾病,如胆管病和胆汁性肝纤维化,这些疾病可能从良性发展为恶性状态,如胆管癌。虽然肝脏类器官研究已经成熟且技术先进,但胆管类器官(BDO)具有巨大潜力。BDO能够准确模拟胆管的生理结构和功能,使其成为体外胆管疾病研究的宝贵工具。在此,我们综述BDO模型的发展,重点关注干细胞来源的类器官和组织来源的类器官。我们还阐述了培养策略和细胞外支架在支持类器官生长和稳定性方面的作用,包括微环境的细胞成分和物理化学因素的影响。此外,我们讨论了BDO在胆管发育、疾病建模、再生医学和药物筛选中的应用。此外,我们强调BDO生物样本库和个性化医学的变革潜力,这有助于为创新治疗策略和个性化医学铺平道路。最后,我们总结了BDO技术的当前和未来进展,突出了人工智能、3D生物打印和芯片上类器官系统等新兴技术的整合。这些技术在显著增强胆管疾病领域的临床和研究应用方面具有巨大潜力。

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