Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer
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Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer. / Grützmeier, Simon Ezban; Kovacevic, Bojan; Vilmann, Peter; Rift, Charlotte Vestrup; Melchior, Linea Cecilie; Holmström, Morten Orebo; Brink, Lene; Hassan, Hazem; Karstensen, John Gásdal; Grossjohann, Hanne; Chiranth, Deepthi; Toxværd, Anders; Hansen, Carsten Palnæs; Høgdall, Estrid; Hasselby, Jane Preuss; Klausen, Pia.
I: Cancers, Bind 15, Nr. 14, 3677, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 373883331