Label-Free Imaging Analysis of Patient-Derived Cholangiocarcinoma Organoids after Sorafenib Treatment

Koch, Michael and Nickel, Sandra and Lieshout, Ruby and Lissek, Susanna M. and Leskova, Martina and van der Laan, Luc J. W. and Verstegen, Monique M. A. and Christ, Bruno and Pampaloni, Francesco (2022) Label-Free Imaging Analysis of Patient-Derived Cholangiocarcinoma Organoids after Sorafenib Treatment. CELLS, 11 (22): 3613. ISSN , 2073-4409

Full text not available from this repository. (Request a copy)

Abstract

Monitoring tumor growth dynamics is crucial for understanding cancer. To establish an in vitro method for the continuous assessment of patient-specific tumor growth, tumor organoids were generated from patients with intrahepatic CCA (iCCA). Organoid growth was monitored for 48 h by label-free live brightfield imaging. Growth kinetics were calculated and validated by MTS assay as well as immunohistochemistry of Ki67 to determine proliferation rates. We exposed iCCA organoids (iCCAOs) and non-tumor intrahepatic cholangiocyte organoids (ICOs) to sub-therapeutic concentrations of sorafenib. Monitoring the expansion rate of iCCAOs and ICOs revealed that iCCAO growth was inhibited by sorafenib in a time- and dose-dependent fashion, while ICOs were unaffected. Quantification of the proliferation marker Ki67 confirmed inhibition of iCCAO growth by roughly 50% after 48 h of treatment with 4 mu M sorafenib. We established a robust analysis pipeline combining brightfield microscopy and a straightforward image processing approach for the label-free growth monitoring of patient-derived iCCAOs. Combined with bioanalytical validation, this approach is suitable for a fast and efficient high-throughput drug screening in tumor organoids to develop patient-specific systemic treatment options.

Item Type: Article
Uncontrolled Keywords: LIGHT-SHEET MICROSCOPY; LIVER; CANCER; ESTABLISHMENT; EXPERIENCE; RESISTANCE; DIAGNOSIS; CULTURE; CELLS; GUIDE; label-free live imaging; brightfield microscopy; tumor organoids; primary liver cancer; intrahepatic cholangiocarcinoma; sorafenib
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Feb 2024 14:43
Last Modified: 29 Feb 2024 14:43
URI: https://pred.uni-regensburg.de/id/eprint/58214

Actions (login required)

View Item View Item