Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma

Sougat Misra, Carlos F. Moro, Marco Del Chiaro, Soledad Pouso, A. Sebestyén, Matthias Löhr, Mikael Björnstedt, Caroline S. Verbeke

Research output: Contribution to journalArticle

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, which is mainly due to late diagnosis and profound resistance to treatment. The latter is to a large extent attributed to the tumor stroma that is exceedingly prominent in PDAC and engages in complex interactions with the cancer cells. Hence, relevant preclinical models of PDAC should also include the tumor stroma. We herein describe the establishment and functional validation of an ex vivo organotypic culture of human PDAC that is based on precision-cut tissue slices from surgical specimens and reproducibly recapitulates the complex cellular and acellular composition of PDAC, including its microenvironment. The cancer cells, tumor microenvironment and interspersed remnants of nonneoplastic pancreas contained in these 350 µm thick slices maintained their structural integrity, phenotypic characteristics and functional activity when in culture for at least 4 days. In particular, tumor cell proliferation persisted and the grade of differentiation and morphological phenotype remained unaltered. Cultured tissue slices were metabolically active and responsive to rapamycin, an mTOR inhibitor. This culture system is to date the closest surrogate to the parent carcinoma and harbors great potential as a drug sensitivity testing system for the personalized treatment of PDAC.

Original languageEnglish
Article number2133
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Adenocarcinoma
Neoplasms
Cellular Microenvironment
Tumor Microenvironment
Delayed Diagnosis
Sirolimus
Pancreas
Cell Proliferation
Carcinoma
Phenotype
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

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Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma. / Misra, Sougat; Moro, Carlos F.; Del Chiaro, Marco; Pouso, Soledad; Sebestyén, A.; Löhr, Matthias; Björnstedt, Mikael; Verbeke, Caroline S.

In: Scientific reports, Vol. 9, No. 1, 2133, 01.12.2019.

Research output: Contribution to journalArticle

Misra, S, Moro, CF, Del Chiaro, M, Pouso, S, Sebestyén, A, Löhr, M, Björnstedt, M & Verbeke, CS 2019, 'Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma', Scientific reports, vol. 9, no. 1, 2133. https://doi.org/10.1038/s41598-019-38603-w
Misra, Sougat ; Moro, Carlos F. ; Del Chiaro, Marco ; Pouso, Soledad ; Sebestyén, A. ; Löhr, Matthias ; Björnstedt, Mikael ; Verbeke, Caroline S. / Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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