Cold Atmospheric Plasma Induces a Predominantly Necrotic Cell Death via the Microenvironment.
BACKGROUND
Cold plasma is a partially ionized gas generated by an electric field at atmospheric pressure that was initially used in medicine for decontamination and sterilization of inert surfaces. There is currently growing interest in using cold plasma for more direct medical applications, mainly due to the possibility of tuning it to obtain selective biological effects in absence of toxicity for surrounding normal tissues,. While the therapeutic potential of cold plasma in chronic wound, blood coagulation, and cancer treatment is beginning to be documented, information on plasma/cell interaction is so far limited and controversial.


RESULTS
Using normal primary human fibroblast cultures isolated from oral tissue, we sought to decipher the effects on cell behavior of a proprietary cold plasma device generating guided ionization waves carried by helium. In this model, cold plasma treatment induces a predominantly necrotic cell death. Interestingly, death is not triggered by a direct interaction of the cold plasma with cells, but rather via a transient modification in the microenvironment. We show that modification of the microenvironment redox status suppresses treatment toxicity and protects cells from death. Moreover, necrosis is not accidental and seems to be an active response to an environmental cue, as its execution can be inhibited to rescue cells.


CONCLUSIONS
These observations will need to be taken into account when studying in vitro plasma/cell interaction and may have implications for the design and future evaluation of the efficacy and safety of this new treatment strategy.
Centre de Recherche en Cancérologie de Lyon, UMR5286 CNRS/INSERM/Université Lyon 1 UCBL, Lyon, France; Faculté d'Odontologie de Lyon, Université Lyon 1, Lyon, France.
François
F
Virard
Université Paul-Sabatier Toulouse III, Faculté de Chirurgie Dentaire de Toulouse, Toulouse, France; CHU de Toulouse, Toulouse, France.
Sarah
S
Cousty
CHU de Toulouse, Toulouse, France; Laboratoire Hématologie, Hôpital Rangueil, TSA 50032, Toulouse, France.
Jean-Pierre
JP
Cambus
CHU de Toulouse, Toulouse, France; Université Paul-Sabatier Toulouse III, Faculté de Pharmacie UMR 152 IRD-UPS PHARMA-DEV, Toulouse, France.
Alexis
A
Valentin
Université Paul-Sabatier Toulouse III, Faculté de Chirurgie Dentaire de Toulouse, Toulouse, France; CHU de Toulouse, Toulouse, France.
Philippe
P
Kémoun
LCABIE-IPREM / UMR 5254, Université de Pau et des Pays de l'Adour Pau, Pau, France.
Franck
F
Clément
D017209:Apoptosis / Q000187:drug effects; D001274:Atmospheric Pressure; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D009336:Necrosis / Q000139:chemically induced*; D058626:Plasma Gases / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D058626:Plasma Gases; D017382:Reactive Oxygen Species