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DOI: 10.1055/s-0044-1801013
A Biliary Organoid Approach to Study the Transition from Primary Sclerosing Cholangitis to Cholangiocarcinoma
Background: The pathomechanisms underlying cholangiocarcinoma (CCC) from primary sclerosing cholangitis (PSC) remain unclear. There is an urgent need for innovative models to study the malignant transformation of PSC to CCC. 3D cell culture models, such as organoids, have shown great potential in studying PSC and CCC. We have established a novel protocol to generate organoids from bile and bile duct biopsies and now aim to apply this model to investigate PSC/CCC.
Methods: Bile fluid and bile duct biopsies from patients with PSC, CCC, and non-PSC/CCC were used to generate organoids. Organoids derived from bile fluid were characterized to determine their cellular origin using cholangiocyte- and hepatocyte-specific markers, which were analyzed by qPCR, Western blot, and immunofluorescence.
Results: Organoids were successfully generated from bile duct biopsies across different patient groups (control, PSC, CCC). Additionally, a novel protocol was developed for generating organoids from bile fluid, offering a less invasive alternative to biopsy collection. A panel of markers (Epcam, Cytokeratin-19, and Sox9) confirmed that the cells within the organoids are cholangiocytes.
Conclusion: Understanding the pathophysiological mechanisms driving the progression of PSC to CCC is critical for early diagnosis and the development of novel therapies. We successfully established a biliary organoid model, including a new method of generating organoids from bile fluid, which is less invasive. This model provides a platform for further research into PSC-CCC transformation and holds potential for creating highly personalized, patient-specific therapeutic approaches.
Publication History
Article published online:
20 January 2025
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