TY - JOUR

T1 - Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer

AU - Grützmeier, Simon Ezban

AU - Kovacevic, Bojan

AU - Vilmann, Peter

AU - Rift, Charlotte Vestrup

AU - Melchior, Linea Cecilie

AU - Holmström, Morten Orebo

AU - Brink, Lene

AU - Hassan, Hazem

AU - Karstensen, John Gásdal

AU - Grossjohann, Hanne

AU - Chiranth, Deepthi

AU - Toxværd, Anders

AU - Hansen, Carsten Palnæs

AU - Høgdall, Estrid

AU - Hasselby, Jane Preuss

AU - Klausen, Pia

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - cancer-associated fibroblasts

KW - co-cultures

KW - disease modelling

KW - EUS-FNB

KW - pancreatic cancer

KW - patient-derived organoids

KW - personalized medicine

UR - http://www.scopus.com/inward/record.url?scp=85167856554&partnerID=8YFLogxK

U2 - 10.3390/cancers15143677

DO - 10.3390/cancers15143677

M3 - Journal article

C2 - 37509338

AN - SCOPUS:85167856554

VL - 15

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 14

M1 - 3677

ER -