Gallbladder tissue and cholangiocyte organoids biorepository
Gallbladder cancer (GBC) while rare worldwide has a high prevalence in India. Pathogenesis is unclear and outcomes poor. Patient derived gallbladder cholangiocyte organoids (GCO) were developed and serially propagated from surgically resected tissues with 15 normal; 58 inflamed;12 xanthogranulomatous cholecystitis (XGC); 5 pre-invasive neoplasm and 13 invasive malignant gallbladder pathologies. Protocol optimization helped achieve 58% (69/119) success in GCO generation and expansion. GCOs maintained tight junction integrity, P-gp pump and enzymatic activity, expressed gene and protein markers, preserved histological features and patient-specific genetic variations of primary tissue. Cryopreserved living GCOs from 62 patients, along with primary tissue and high-quality DNA, RNA and protein derivatives have been banked. Gene expression analyses of tissues showed XGC samples clustered with malignant group separated from benign pathologies. Derivative GCOs showed a similar clustering. Hallmark pathway analyses suggest XGC as a transitioning pre-malignant state. GCOs are a promising model to investigate the pathogenesis of GBC.