Electroporation does not affect human dermal fibroblast proliferation and migration properties directly but indirectly via the secretome

Sara Gouarderes (1, 2) , Layal Doumard (3) , Patricia Vicendo (1, 2) , Anne-Françoise Mingotaud (1, 2) , Marie-Pierre Rols (3) , Laure Gibot (1, 2)

1 IMRCP - Interactions moléculaires et réactivité chimique et photochimique
2 IMRCP - IDeAS - IMRCP - Interfaces Dynamiques et Assemblages Stimulables
3 IPBS - Institut de pharmacologie et de biologie structurale

Aesthetic wound healing is often experienced by patients after electrochemotherapy. We hypothesized that pulsed electric fields applied during electrochemotherapy (ECT) or gene electrotransfer (GET) protocols could stimulate proliferation and migration of human cutaneous cells, as described in protocols for electrostimulation of wound healing. We used videomicroscopy to monitor and quantify in real time primary human dermal fibroblast behavior when exposed in vitro to ECT and GET electric parameters, in terms of survival, proliferation and migration in a calibrated scratch wound assay. Distinct electric field intensities were applied to allow gradient in cell electropermeabilization while maintaining reversible permeabilization conditions, in order to mimic in vivo heterogeneous electric field distribution of complex tissues. Neither galvanotaxis nor statistical modification of fibroblast migration were observed in a calibrated scratch wound assay after application of ECT and GET parameters. The only effect on proliferation was observed under the strongest GET conditions, which drastically reduced the number of fibroblasts through induction of mitochondrial stress and apoptosis. Finally, we found that 24 h-conditioned cell culture medium by electrically stressed fibroblasts tended to increase the migration properties of cells that were not exposed to electric field. RT-qPCR array indicated that several growth factor transcripts were strongly modified after electroporation.

Mots clés: Scratch wound; Wound healing; Gene electrotransfer; Electrochemotherapy; Conditioned medium; Bystander effect

Domaines: Biologie cellulaire; Biophysique [physics.bio-ph]; Ingénierie biomédicale

Sara Gouarderes, Layal Doumard, Patricia Vicendo, Anne-Françoise Mingotaud, Marie-Pierre Rols, et al.. Electroporation does not affect human dermal fibroblast proliferation and migration properties directly but indirectly via the secretome. Bioelectrochemistry, 2020, 134, pp.107531. ⟨10.1016/j.bioelechem.2020.107531⟩. ⟨hal-02560967⟩