Organoids at the PUB: The Porcine Urinary Bladder Serves as a Pancreatic Niche for Advanced Cancer Modeling
| Autor: | Michael Karl Melzer, Markus Breunig, Frank Arnold, Felix Wezel, Anca Azoitei, Elodie Roger, Jana Krüger, Jessica Merkle, Lena Schütte, Yazid Resheq, Mark Hänle, Viktor Zehe, Friedemann Zengerling, Ninel Azoitei, Lukas Klein, Frederike Penz, Shiv K. Singh, Thomas Seufferlein, Meike Hohwieler, Christian Bolenz, Cagatay Günes, Johann Gout, Alexander Kleger |
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| Rok vydání: | 2022 |
| Předmět: |
Organoid
Pancreas Cancer Pancreatic neoplasms Swine Organ culture techniques pancreatic cancer Biomedical Engineering Zelldifferenzierung Pharmaceutical Science organ culture models Urinary bladder Organoids Biomaterials Pluripotent stem cells Induzierte pluripotente Stammzelle Cell differentiation Organkultur Animals Humans ddc:610 stem cell differentiation Bauchspeicheldrüsenkrebs DDC 610 / Medicine & health Carcinoma Pancreatic Ductal |
| Zdroj: | Advanced Healthcare Materials. 11:2102345 |
| ISSN: | 2192-2659 2192-2640 |
| Popis: | 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. publishedVersion |
| Databáze: | OpenAIRE |
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