TY  - JOUR
A1  - Dong, Meng
A1  - Böpple, Kathrin
A1  - Thiel, Julia
A1  - Winkler, Bernd
A1  - Liang, Chunguang
A1  - Schueler, Julia
A1  - Davies, Emma J.
A1  - Barry, Simon T.
A1  - Metsalu, Tauno
A1  - Mürdter, Thomas E.
A1  - Sauer, Georg
A1  - Ott, German
A1  - Schwab, Matthias
A1  - Aulitzky, Walter E.
T1  - Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions
JF  - Cells
N2  - Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air–liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses.
KW  - precision-cut tumor slices
KW  - perfusion culture
KW  - tumor microenvironment
KW  - ovarian tumor
KW  - individual drug responses
KW  - mouse xenografts
KW  - preclinical model
KW  - personalized medicine
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311030
SN  - 2073-4409
VL  - 12
IS  - 5
ER  -