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Karampelias, C. ; Yang, K. ; Farkas, F. ; Sterr, M. ; Molina van Den Bosch, M. ; Renner, S.* ; Fuß, J.* ; von Toerne, C. ; Franzenburg, S.* ; Kin, T.* ; Wolf, E.* ; Kemter, E.* ; Lickert, H.

Benchmarking porcine pancreatic ductal organoids for drug screening applications.

EMBO Mol. Med., DOI: 10.1038/s44321-025-00330-3 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Primary human pancreatic ductal organoids (HPDO) have emerged as a model to study pancreas biology and model disease like pancreatitis and pancreatic cancer. Yet, donor material availability, genetic variability and a lack of extensive benchmarking to healthy and disease pancreas limits the range of applications. To address this gap, we established porcine pancreatic ductal organoids (PPDO) as a system from a reliable, genetically defined and easily obtainable source to model pancreatic ductal/progenitor biology. We benchmarked PPDO to HPDO and primary porcine pancreas using single-cell RNA sequencing (scRNA-Seq). We observed no overt phenotypic differences in PPDO derived from distinct developmental stages using extensive proteomics profiling, with a WNT/basal cell signaling enriched population characterizing PPDO. PPDO exhibited differentiation potential towards mature ductal cells and limited potential towards endocrine lineages. We used PPDO as a chemical screening platform to assess the safety of FDA-approved drugs and showed conserved toxicity of statins and α-adrenergic receptor inhibitors between PPDO and HPDO cultures. Overall, our results highlight the PPDO as a model for mammalian duct/progenitor applications.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Chemical Screen ; Cross-species Comparison ; Omics Profile ; Pancreatic Ductal Organoids ; Porcine Pancreas ; Proteome Profile ; Scrna-seq Profile; Beta-cells; Progenitor Cells; Mouse Pancreas; Stem-cells; In-vitro; Adult; Expansion; Differentiation; Establishment; Expression
ISSN (print) / ISBN 1757-4676
e-ISSN 1757-4684
Journal EMBO Molecular Medicine
Publisher Wiley
Publishing Place Chichester
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
CF Metabolomics & Proteomics (CF-MPC)
Grants
Deutsche Forschungsgemeinschaft (DFG)
Deutsches Zentrum fr Diabetesforschung (DZD)
Innovative Health Initiative NHPig
Helmholtz Society
Breakthrough Type 1 DIabetes
Helmholtz Research school for Diabetes funded by Helmholtz Association - Initiative and Networking Fund (IVF)
Alexander von Humboldt-Stiftung (AvH)