GSE178148
Cold atmospheric plasma affects stem cell renewal and differentiation and is associated with a regeneration process in an intestinal organoid culture model
Cold atmospheric plasma (CAP) has recently been proposed as an anti-cancer therapy, mainly driven by the concentration of reactive oxygen and nitrogen species (RONS), whereas several studies suggest its selectivity on cancer cells. However, the underlying mechanisms of this “selectivity” are largely poorly understood and rely exclusively on 2D (dimensional) unicellular monolayers, which do not recapitulate the in vivo epithelial context. In this study, we aimed to evaluate phenotypically and transcriptomically the effect of different modalities of CAP's application (direct, indirect and plasma activated medium) on intestinal organoids derived from wild type (WT), VillinCreERT2/Apc floxflox and VillinCreERT2/Apc WT adult mice.  The phenotype analysis of different modalities (direct, indirect, plasma activated medium) of CAP's application revealed that direct and indirect CAP treatment decrease WT intestinal organoid survival associated to a predominance of spheroids organoids, this reduction in survival was not observed for organoids derived from Villin CreERT2/Apc flox flox mice. Moreover, transcriptome analyses of control's organoids showed that indirect and plasma activated applications induced a transcriptomic reprogramming, highlighted by a decrease of intestinal stem cell pool, cell cycle arrest, cell death, altogether associated to a regeneration repair process. These results have been validated at the protein level. In conclusion, in a 3D organoid model, the selectivity of CAP on cancer cells does not seem to be confirmed. Overall design: mRNA profiles of duodenum derived organoids from wild type mice at adult stage exposed to different modalities of CAP.