Organoids at the PUB : the porcine urinary bladder serves as a pancreatic niche for advanced cancer modeling
peer-reviewed
Erstveröffentlichung
2022-02-18Authors
Melzer, Michael Karl
Breuning, Markus
Arnold, Frank
Wezel, Felix
Azoitei, Anca
Wissenschaftlicher Artikel
Published in
Advanced Healthcare Materials ; 11 (2022), 11. - Art.-Nr. 2102345. - ISSN 2192-2640. - eISSN 2192-2659
Link to original publication
https://dx.doi.org/10.1002/adhm.202102345Institutions
UKU. Klinik für Urologie und KinderurologieUKU. Klinik für Innere Medizin I
Document version
published version (publisher's PDF)Abstract
Despite intensive research and progress in personalized medicine, pancreatic ductal adenocarcinoma remains one of the deadliest cancer entities. Pancreatic duct-like organoids (PDLOs) derived from human pluripotent stem cells (PSCs) or pancreatic cancer patient-derived organoids (PDOs) provide unique tools to study early and late stage dysplasia and to foster personalized medicine. However, such advanced systems are neither rapidly nor easily accessible and require an in vivo niche to study tumor formation and interaction with the stroma. Here, the establishment of the porcine urinary bladder (PUB) is revealed as an advanced organ culture model for shaping an ex vivo pancreatic niche. This model allows pancreatic progenitor cells to enter the ductal and endocrine lineages, while PDLOs further mature into duct-like tissue. Accordingly, the PUB offers an ex vivo platform for earliest pancreatic dysplasia and cancer if PDLOs feature KRASG12D mutations. Finally, it is demonstrated that PDOs-on-PUB i) resemble primary pancreatic cancer, ii) preserve cancer subtypes, iii) enable the study of niche epithelial crosstalk by spiking in pancreatic stellate and immune cells into the grafts, and finally iv) allow drug testing. In summary, the PUB advances the existing pancreatic cancer models by adding feasibility, complexity, and customization at low cost and high flexibility.
DFG Project THU
Differenzierung von Pankreasgängen und -azini aus humanen pluripotenten Stammzellen zur Untersuchung des Pankreaskarzinoms / DFG / 426789343 [KL 2544/1-1]
GRK 2254 / HEIST / Heterogenität und Evolution in soliden Tumoren (HEIST) / DFG / 288342734 [KL 2544/1-2]
Monogenetische Formen des juvenil sich manifestierenden Diabetes: neue Schritte in Richtung β-Zellentwicklung, -funktion und -überleben / DFG / 406674944 [KL 2544/5-1]
Zelluläre Plastizität im Pankreas - vom Krankheitsmodell über Gewebserneuerung zur personalisierten Medizin / DFG / 426789149 [KL 2544/6-1 ; KL 2544/7-1]
Selektive Deletion der Ataxia-telangiektasia mutiert Kinase (Atm) zur Analyse von Tumorheterogenität im Pankreaskarzinom / DFG / 452061284 [PE 3337/1-1]
GRK 2254 / HEIST / Heterogenität und Evolution in soliden Tumoren (HEIST) / DFG / 288342734 [KL 2544/1-2]
Monogenetische Formen des juvenil sich manifestierenden Diabetes: neue Schritte in Richtung β-Zellentwicklung, -funktion und -überleben / DFG / 406674944 [KL 2544/5-1]
Zelluläre Plastizität im Pankreas - vom Krankheitsmodell über Gewebserneuerung zur personalisierten Medizin / DFG / 426789149 [KL 2544/6-1 ; KL 2544/7-1]
Selektive Deletion der Ataxia-telangiektasia mutiert Kinase (Atm) zur Analyse von Tumorheterogenität im Pankreaskarzinom / DFG / 452061284 [PE 3337/1-1]
Project uulm
Blockade der DNA-Reparatur treibt Krebszelle in den Tod - Präklinische Studie: Kombinationstherapie hemmt ATM-mutierten Pankreas-Tumor / Deutsche Krebshilfe / 70111879
Is supplemented by
https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fadhm.202102345&file=adhm202102345-sup-0001-SuppMat.pdfhttps://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fadhm.202102345&file=adhm202102345-sup-0002-TableS1.xlsx
Subject headings
[GND]: Bauchspeicheldrüsenkrebs | Induzierte pluripotente Stammzelle | Zelldifferenzierung | Organkultur | Organoid[LCSH]: Pancreas; Cancer
[MeSH]: Pancreatic neoplasms | Urinary bladder | Pluripotent stem cells | Cell differentiation | Organ culture techniques | Organoids
[Free subject headings]: organ culture models | pancreatic cancer | stem cell differentiation
[DDC subject group]: DDC 610 / Medicine & health
Metadata
Show full item recordDOI & citation
Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-48924
Melzer, Michael Karl et al. (2023): Organoids at the PUB : the porcine urinary bladder serves as a pancreatic niche for advanced cancer modeling. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-48924
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