Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer.

Autor: Grützmeier SE; Gastro Unit, Endoscopic Division, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark., Kovacevic B; Gastro Unit, Endoscopic Division, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark.; Department of Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Vilmann P; Gastro Unit, Endoscopic Division, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark., Rift CV; Department of Pathology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Melchior LC; Department of Pathology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Holmström MO; National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark.; Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark., Brink L; Gastro Unit, Endoscopic Division, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark., Hassan H; Gastro Unit, Endoscopic Division, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark., Karstensen JG; Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.; Pancreatitis Centre East, Gastroenterology Unit, Copenhagen University Hospital-Amager and Hvidovre, 2650 Hvidovre, Denmark., Grossjohann H; Department of Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Chiranth D; Department of Pathology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Toxværd A; Department of Pathology, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark., Hansen CP; Department of Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Høgdall E; Department of Pathology, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark., Hasselby JP; Department of Pathology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark.; Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark., Klausen P; Gastro Unit, Endoscopic Division, Copenhagen University Hospital Herlev and Gentofte, 2730 Herlev, Denmark.; Department of Pathology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Jul 19; Vol. 15 (14). Date of Electronic Publication: 2023 Jul 19.
DOI: 10.3390/cancers15143677
Abstrakt: Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived from endoscopic ultrasound-guided fine-needle biopsies (EUS-FNBs) for potential use in drug screening applications. Co-cultures were established, and growth was compared to monocultures using image metrics and a commercially available assay. We were able to establish and expand validated malignant PDTOs from 19.2% of adenocarcinomas from EUS-FNBs. CAFs could be established from 25% of the samples. The viability of PDTOs in the mixed cell co-culture could be isolated using image metrics. The addition of CAFs promoted PDTO growth in half of the established co-cultures. These results show that co-cultures can be established from tiny amounts of tissue provided by EUS-FNB. An increased growth of PDTOs was shown in co-cultures, suggesting that the present setup successfully models CAF-PDTO interaction. Furthermore, we demonstrated that standard validation techniques may be insufficient to detect contamination with normal cells in PDTO cultures established from primary tumor core biopsies.
Competing Interests: P.V. is a consultant to Medi-Globe GmbH. The other authors declare that they have no financial conflicts of interest with regard to the content of this report.
Databáze: MEDLINE
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