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

验证新型 EUS-FNB 衍生类器官共培养系统对胰腺癌患者进行药物筛选的效果

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作者:Simon Ezban Grützmeier, Bojan Kovacevic, Peter Vilmann, Charlotte Vestrup Rift, Linea Cecilie Melchior, Morten Orebo Holmström, Lene Brink, Hazem Hassan, John Gásdal Karstensen, Hanne Grossjohann, Deepthi Chiranth, Anders Toxværd, Carsten Palnæs Hansen, Estrid Høgdall, Jane Preuss Hasselby, Pia Klau

Abstract

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.

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