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<p>Biliary tract cancer, particularly cholangiocarcinoma (CCA), poses significant challenges due to its aggressive nature, heterogeneous characteristics, and limited treatment options. The interplay between hepatic stellate cells (HSCs) and CCA cells (CCAs) in the microenvironment plays a critical role in tumor progression and drug resistance. However, current models often struggle to effectively mimic the complex microenvironment that drives CCA malignancy and drug resistance. To bridge this gap, we engineered a 3D biomimetic cholangiocarcinoma-on-a-chip (CoaC) platform using microfluidic technology. This system incorporates a microporous membrane lined with vascular endothelial cells and enables the co-culture of HSCs and CCAs in a Matrigel matrix, offering a more physiologically accurate setting for CCA than traditional plate-based models. A multi-channel syringe pump is linked to sustain dynamic cell culture and drug delivery. Using this platform, we evaluated the efficacy of resveratrol (RV) and combination with cisplatin (CIS), which showed that the apoptosis rate of HUCCT-1 cells in the co-culture group was significantly reduced compared to the mono-culture group at concentrations ranging from 10 µmol/L to 200 µmol/L. We further assessed the synergistic efficacy of RV combined with CIS in inhibiting CCAs. Additionally, we observed that HSCs decreased the apoptosis rate of tumor cells, thereby reducing the drug sensitivity of CCAs, revealing the crucial role of HSCs in CCA drug therapy. This study introduces a robust tumor-on-chip co-culture model for CCA, offering a powerful tool for improved drug evaluation analysis and holding significant potential for advancing CCA patients’ personalized therapeutic strategies.</p>

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Development of a Three-Dimensional Cholangiocarcinoma-on-a-Chip for Improved Drug Response Analysis

  • 期刊论文

  • 发表日期：

    2026年7月11日

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  • Yuhan Fang,
  • Caiming Xu,
  • Zihe Gao,
  • Yahui Ji,
  • Xue Bai,
  • Xianming Liu,
  • Yan Bi,
  • Xinmiao Liang,
  • Yao Lu,
  • Guixin Zhang

摘要

Biliary tract cancer, particularly cholangiocarcinoma (CCA), poses significant challenges due to its aggressive nature, heterogeneous characteristics, and limited treatment options. The interplay between hepatic stellate cells (HSCs) and CCA cells (CCAs) in the microenvironment plays a critical role in tumor progression and drug resistance. However, current models often struggle to effectively mimic the complex microenvironment that drives CCA malignancy and drug resistance. To bridge this gap, we engineered a 3D biomimetic cholangiocarcinoma-on-a-chip (CoaC) platform using microfluidic technology. This system incorporates a microporous membrane lined with vascular endothelial cells and enables the co-culture of HSCs and CCAs in a Matrigel matrix, offering a more physiologically accurate setting for CCA than traditional plate-based models. A multi-channel syringe pump is linked to sustain dynamic cell culture and drug delivery. Using this platform, we evaluated the efficacy of resveratrol (RV) and combination with cisplatin (CIS), which showed that the apoptosis rate of HUCCT-1 cells in the co-culture group was significantly reduced compared to the mono-culture group at concentrations ranging from 10 µmol/L to 200 µmol/L. We further assessed the synergistic efficacy of RV combined with CIS in inhibiting CCAs. Additionally, we observed that HSCs decreased the apoptosis rate of tumor cells, thereby reducing the drug sensitivity of CCAs, revealing the crucial role of HSCs in CCA drug therapy. This study introduces a robust tumor-on-chip co-culture model for CCA, offering a powerful tool for improved drug evaluation analysis and holding significant potential for advancing CCA patients’ personalized therapeutic strategies.