COLD ATMOSPHERIC PLASMA DIFFERENTIALLY AFFECTS CELL RENEWAL AND DIFFERENTIATION OF STEM CELLS AND APC-DEFICIENT-DERIVED TUMOR CELLS IN INTESTINAL ORGANOIDS

Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoi...

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Published inbioRxiv
Main Authors Hadefi, Alia, Leprovots, Morgane, Thulliez, Max, Bastin, Orianne, Lefort, Anne, Libert, Frederick, Nonclercq, Antoine, Delchambre, Alain, Reniers, Francois, Deviere, Jacques, Garcia, Marie-Isabelle
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 15.10.2021
Subjects
Adenomatous polyposis coli
Adenomatous polyposis coli protein
Antioxidants
Apoptosis
Cell culture
Cell death
Cell differentiation
Cytotoxicity
Fetuses
Medical innovations
Organoids
Oxidative stress
Small intestine
Stem cell transplantation
Stem cells
Tumor cells
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Summary:Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with global response to oxidative stress, fetal-like regeneration reprogramming and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology. Competing Interest Statement The authors have declared no competing interest. Footnotes * Acknowledgement section added: We acknowledge the contribution of Maryam Marefati for tamoxifen injections.
DOI:10.1101/2021.10.13.464287