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Cold Atmospheric Plasma Differentially Affects Cell Renewal and Differentiation of Stem Cells and Apc-Deficient-Derived Tumor Cells in Intestinal Organoids

View ORCID ProfileAlia Hadefi, View ORCID ProfileMorgane Leprovots, View ORCID ProfileMax Thulliez, View ORCID ProfileOrianne Bastin, Anne Lefort, Frédérick Libert, View ORCID ProfileAntoine Nonclercq, View ORCID ProfileAlain Delchambre, View ORCID ProfileFrançois Reniers, View ORCID ProfileJacques Devière, View ORCID ProfileMarie-Isabelle Garcia
doi: https://doi.org/10.1101/2021.10.13.464287
Alia Hadefi
1Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, 1070, Brussels, Belgium
2Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Laboratory of Experimental Gastroenterology, Route de Lennik 808, 1070, Brussels, Belgium
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Morgane Leprovots
1Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, 1070, Brussels, Belgium
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Max Thulliez
3Bio-, Electro- and Mechanical- system (BEAMS), Biomed Group, Ecole polytechnique de Bruxelles, av. F.D. Roosevelt 50 CP165/56 - 1050 Brussels, Belgium
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Orianne Bastin
3Bio-, Electro- and Mechanical- system (BEAMS), Biomed Group, Ecole polytechnique de Bruxelles, av. F.D. Roosevelt 50 CP165/56 - 1050 Brussels, Belgium
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Anne Lefort
1Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, 1070, Brussels, Belgium
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Frédérick Libert
1Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, 1070, Brussels, Belgium
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Antoine Nonclercq
3Bio-, Electro- and Mechanical- system (BEAMS), Biomed Group, Ecole polytechnique de Bruxelles, av. F.D. Roosevelt 50 CP165/56 - 1050 Brussels, Belgium
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Alain Delchambre
3Bio-, Electro- and Mechanical- system (BEAMS), Biomed Group, Ecole polytechnique de Bruxelles, av. F.D. Roosevelt 50 CP165/56 - 1050 Brussels, Belgium
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François Reniers
4Chemistry of Surfaces, Interfaces, and Nanomaterials, ChemSIN cp 255, Université libre de Bruxelles, Faculty of Sciences, Brussels, Belgium
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Jacques Devière
2Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Laboratory of Experimental Gastroenterology, Route de Lennik 808, 1070, Brussels, Belgium
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Marie-Isabelle Garcia
1Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, 1070, Brussels, Belgium
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  • For correspondence: Marie.Garcia@ulb.be
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ABSTRACT

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

  • ↵* First co-authors

  • ↵# Second co-authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 14, 2021.
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Cold Atmospheric Plasma Differentially Affects Cell Renewal and Differentiation of Stem Cells and Apc-Deficient-Derived Tumor Cells in Intestinal Organoids
Alia Hadefi, Morgane Leprovots, Max Thulliez, Orianne Bastin, Anne Lefort, Frédérick Libert, Antoine Nonclercq, Alain Delchambre, François Reniers, Jacques Devière, Marie-Isabelle Garcia
bioRxiv 2021.10.13.464287; doi: https://doi.org/10.1101/2021.10.13.464287
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Cold Atmospheric Plasma Differentially Affects Cell Renewal and Differentiation of Stem Cells and Apc-Deficient-Derived Tumor Cells in Intestinal Organoids
Alia Hadefi, Morgane Leprovots, Max Thulliez, Orianne Bastin, Anne Lefort, Frédérick Libert, Antoine Nonclercq, Alain Delchambre, François Reniers, Jacques Devière, Marie-Isabelle Garcia
bioRxiv 2021.10.13.464287; doi: https://doi.org/10.1101/2021.10.13.464287

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