Related Experiment Video
Updated: Jul 3, 2026
Generation of Organoids from Mouse Extrahepatic Bile Ducts
Published on: April 23, 2019
Wnt Stimulation and Inhibition in the Development and Phenotype of Patient-Derived Gallbladder Organoids
Ankita Dutta1,2, Payel Guha1, Akshaya Vijayan Selvarajan3
1Tata Translational Cancer Research Centre, Kolkata, India.
Background:
Gallbladder cancer (GBC) is a highly lethal malignancy with limited experimental models to study disease biology or evaluate therapeutic responses. Although canonical Wnt activation is commonly used for patient-derived organoid (PDO) development and expansion, gallbladder PDOs have also been generated under Wnt-inhibitory conditions. No comparative assessments have determined how Wnt pathway modulation influences gallbladder PDO development, phenotype, or drug response.
Methods:
This study systematically compared the impact of canonical Wnt activation (WNTAct medium containing CHIR99021) versus inhibition (WNTInh medium containing DKK1) on the establishment, propagation, molecular features, and therapeutic responses of PDOs generated from malignant or non-malignant gallbladder tissues derived from the same patient.
Results:
Both media supported successful PDO generation with comparable efficiency, preserving biliary epithelial functions and marker expression. Transcriptomic profiling confirmed selective enrichment of canonical Wnt target genes in PDOs generated in WNTAct cultures. WNTAct conditions enabled markedly superior long-term propagation, whereas WNTInh cultures more consistently retained the dysplastic features in malignant samples. Gemcitabine response assays demonstrated significantly greater drug sensitivity in PDOs grown in WNTAct medium, a phenotype reversible upon media switching but requiring extended adaptation, indicating a dynamic and context-dependent influence of Wnt-signaling on chemotherapeutic vulnerability.
Conclusion:
Collectively, the findings reveal a trade-off between long-term propagation and histological fidelity in gallbladder PDOs and show that Wnt-signaling modulates gemcitabine sensitivity in a reversible manner. This comparative framework provides practical guidance for selecting culture conditions for gallbladder PDO-based disease modeling, and precision oncology applications.
Insights
Wnt pathway modulation impacts gallbladder organoid development and drug response. Wnt activation promotes long-term growth and gemcitabine sensitivity, while inhibition preserves tumor features.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Gallbladder cancer (GBC) is a lethal malignancy lacking adequate experimental models.
- Patient-derived organoids (PDOs) are promising models, but Wnt pathway influence on gallbladder PDOs is uncharacterized.
Purpose of the Study:
- To systematically compare Wnt activation versus inhibition on gallbladder PDO development, phenotype, and drug response.
- To guide selection of culture conditions for GBC modeling and precision oncology.
Main Methods:
- Generated gallbladder PDOs from matched malignant and non-malignant tissues under Wnt-activating (WNT extsuperscript{Act}) and Wnt-inhibiting (WNT extsuperscript{Inh}) conditions.
- Assessed PDO establishment, propagation, molecular features via transcriptomics, and gemcitabine response.
Main Results:
- Both WNT extsuperscript{Act} and WNT extsuperscript{Inh} media yielded functional PDOs with comparable efficiency.
- WNT extsuperscript{Act} supported superior long-term propagation, while WNT extsuperscript{Inh} better retained malignant features.
- PDOs in WNT extsuperscript{Act} medium exhibited significantly higher gemcitabine sensitivity, which was reversible.
Conclusions:
- Wnt signaling modulation presents a trade-off between long-term propagation and histological fidelity in gallbladder PDOs.
- Wnt signaling dynamically influences gemcitabine sensitivity in a reversible manner.
- This study provides a framework for optimizing gallbladder PDO culture for research and clinical applications.
