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

Journal: Cancer letters
Published Date:

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.

Authors

  • Yadi Geng
    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.
  • Ziye Chen
    School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Hepato-Pancreato-Biliary Center, Tsinghua University, Beijing, 102218, China.
  • Tianzi Luo
    Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China.
  • Yakun Liu
    Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China.
  • Siming Kong
    Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China.
  • Xinlong Yan
    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. Electronic address: yxlong2000@bjut.edu.cn.
  • Hui Bai
    College of Veterinary Medicine, Northeast Agricultural University, Harbin 150000, China.
  • Yunfang Wang
    School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Hepato-Pancreato-Biliary Center, Tsinghua University, Beijing, 102218, China; Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China; Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 100084, China. Electronic address: wyfa02717@btch.edu.cn.