Digestive diseases and sciences · 2026
An Annotated Living Organoid Biobank for Studying Gallbladder Diseases and Drug Responses.
СтатьяНазвание и аннотация: Перевод в очереди
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Dutta Ankita, Chowdhury Nandita, Selvarajan Akshaya Vijayan, Guha Payel, Banerjee Pritha, Kar Abhirupa, Sunderam Uma, Ganguli Debdutta, Dutta Trina, Basak Dipjit, Satheeshkumar Smrithi Jayashree, Chandra Shinjini, Ragate Anand Sagar, Krishnan Shekhar, Sen Saugata, Roy Manas Kumar, Banerjee Sudeep, Srinivasan Rajgopal, Roy Paromita, Saha Vaskar, Dutta Anindita, GuhaSarkar Dwijit
Аннотация
BACKGROUND: Gallbladder cancer (GBC) while rare worldwide has a high prevalence in India. Pathogenesis is unclear and outcomes poor. No suitable models are available to study GBC pathogenesis and drug response. The aim of this study was to establish a biobank comprising patient derived organoids (PDOs) from a wide variety of gallbladder diseases including GBC and other rare pathologies.
METHODS: PDOs were developed from surgically resected gallbladders 15 normal; 58 inflamed; 12 xanthogranulomatous cholecystitis (XGC); 5 pre-invasive neoplasm (PIN); and 13 invasive malignant gallbladder pathologies. Marker expressions, functional activity, histological and gene expression analyses were performed to validate the models. Banked PDOs were retrieved and drug assays performed to assess line-specific responses.
RESULTS: Protocol optimization achieved 58% (69/119) and 52% (10/19) success in organoid generation and expansion for all and invasive malignant pathologies, respectively-highest globally for GBC organoids reported to date. Organoids maintained tight junction integrity; P-gp pump and enzymatic activity; preserved tissue-specific gene and protein marker expression; histological features and genetic variations. Besides cryopreserved organoids from 62 patients, primary gallbladder tissue and high-quality DNA, RNA and protein derivatives have been banked. In gene expression analyses of tissue, XGC samples clustered with malignant subtypes, separate from benign pathologies. Derived XGC organoids showed a similar clustering. Enriched Hallmark pathways in XGC support neoplastic changes. Drug response assays demonstrate PDO line-specific response heterogeneity.
CONCLUSION: The developed biobank of PDOs from different gallbladder pathologies provides a promising resource to study gallbladder diseases, investigate the pathogenesis of GBC and study drug responses.
METHODS: PDOs were developed from surgically resected gallbladders 15 normal; 58 inflamed; 12 xanthogranulomatous cholecystitis (XGC); 5 pre-invasive neoplasm (PIN); and 13 invasive malignant gallbladder pathologies. Marker expressions, functional activity, histological and gene expression analyses were performed to validate the models. Banked PDOs were retrieved and drug assays performed to assess line-specific responses.
RESULTS: Protocol optimization achieved 58% (69/119) and 52% (10/19) success in organoid generation and expansion for all and invasive malignant pathologies, respectively-highest globally for GBC organoids reported to date. Organoids maintained tight junction integrity; P-gp pump and enzymatic activity; preserved tissue-specific gene and protein marker expression; histological features and genetic variations. Besides cryopreserved organoids from 62 patients, primary gallbladder tissue and high-quality DNA, RNA and protein derivatives have been banked. In gene expression analyses of tissue, XGC samples clustered with malignant subtypes, separate from benign pathologies. Derived XGC organoids showed a similar clustering. Enriched Hallmark pathways in XGC support neoplastic changes. Drug response assays demonstrate PDO line-specific response heterogeneity.
CONCLUSION: The developed biobank of PDOs from different gallbladder pathologies provides a promising resource to study gallbladder diseases, investigate the pathogenesis of GBC and study drug responses.