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 24h-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.
Introduction: Modern comprehensive studies of tumour microenvironment changes allowed scientists to develop new and more efficient strategies that will improve anticancer drug delivery on site. The tumour microenvironment, especially the dense extracellular matrix, has a recognised capability to hamper the penetration of conventional drugs. Development and co-applications of strategies aiming at remodelling the tumour microenvironment are highly demanded to improve drug delivery at the Chemophototherapy, the combination of phototherapy and chemotherapy, is an efficient strategy to induce tumour vascular permeability and ensuing drug delivery to tumours. Standalone or co-applied physical strategies to disrupt the dense tumour extracellular matrix or to mediate vascular permeability may be of major interest to improve drug delivery at the tumour site in a therapeutic prospect.
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