Kreiner, P. and Eggenhofer, Elke and Schneider, L. and Rejas, C. and Goetz, M. and Bogovic, Niklas and Brunner, Stefan M. and Evert, Katja and Schlitt, Hans J. and Geissler, Edward and Junger, Henrik (2024) Extrahepatic Bile Duct Organoids as a Model to Study Ischemia/Reperfusion Injury During Liver Transplantation. TRANSPLANT INTERNATIONAL, 37: 13212. ISSN 0934-0874, 1432-2277
Full text not available from this repository. (Request a copy)Abstract
Biliary complications are still a major cause for morbidity and mortality after liver transplantation (LT). Ischemia/reperfusion injury (IRI) leads to disruption of the biliary epithelium. We introduce a novel model to study the effect of IRI on human cholangiocytes using extrahepatic cholangiocyte organoids (ECOs). Extrahepatic bile duct tissue was collected during LT at static cold storage and after reperfusion (n = 15); gallbladder tissue was used for controls (n = 5). ECOs (n = 9) were cultured from extrahepatic biliary tissue, with IRI induced in an atmosphere of 95% air (nitrogen), 1% O2 and 5% CO(2 )for 48 h, followed by 24 h of reoxygenation. Qualitative and quantitative histology and qRT-PCR were performed to discern phenotype, markers of hypoxia, programmed cell death and proliferation. ECOs self-organized into circular structures resembling biliary architecture containing cholangiocytes that expressed EpCAM, CK19, LGR5 and SOX-9. After hypoxia, ECOs showed increased expression of VEGF A (p < 0.0001), SLC2A1 (p < 0.0001) and ACSL4 (p < 0.0001) to indicate response to hypoxic damage and subsequent programmed cell death. Increase in cyclin D1 (p < 0.0001) after reoxygenation indicated proliferative activity in ECOs. Therefore, ECO structure and response to IRI are comparable to that found in-vivo, providing a suitable model to study IRI of the bile duct in-vitro.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BILIARY COMPLICATIONS; DONOR LIVERS; STEM-CELLS; HIF-1-ALPHA; VEGF; REGENERATION; HOMEOSTASIS; FERROPTOSIS; EXPRESSION; STRICTURES; regenerative medicine; organoids; liver transplant; cholangiopathy; cholangiocyte organoids |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2025 08:13 |
| Last Modified: | 15 Jul 2025 08:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63386 |
Actions (login required)
 |
View Item |
