Abstract
Pulsed electric field treatment has increased over the last few decades with successful translation from in vitro studies into different medical treatments like electrochemotherapy, irreversible electroporation for tumor and cardiac tissue ablation and gene electrotransfer for gene therapy and DNA vaccination. Pulsed electric field treatments are efficient but localized often requiring repeated applications to obtain results due to partial response and recurrence of disease. While these treatment times are several orders of magnitude lower than conventional biochemical treatment, it has been recently suggested that cells may become resistant to electroporation in repetitive treatments. In our study, we evaluate this possibility of developing adaptive resistance in cells exposed to pulsed electric field treatment over successive lifetimes. Mammalian cells were exposed to electroporation pulses for 30 generations. Every 5th generation was analyzed by determining permeabilization and survival curve. No statistical difference between cells in control and cells exposed to pulsed electric field treatment was observed. We offer evidence that electroporation does not affect cells in a way that they would become less susceptible to pulsed electric field treatment. Our findings indicate pulsed electric field treatment can be used in repeated treatments with each treatment having equal efficiency to the initial treatment.
Highlights
Pulsed electric field treatment has increased over the last few decades with successful translation from in vitro studies into different medical treatments like electrochemotherapy, irreversible electroporation for tumor and cardiac tissue ablation and gene electrotransfer for gene therapy and DNA vaccination
pulsed electric field (PEF) treatment including reversible (DNA vaccination, electrochemotherapy) and irreversible electroporation stimulates sensory nerves, the procedure can be painful for patients[25,26]
Permeabilization and survival curves (8 × 100 μs, 1 Hz, 0–600 V) were determined for 1st, 5th, 10th, 15th, 20th, 25th and 30th generation in three experimental groups: CTRL- never exposed to pulse treatment, CTRL + EP - exposed to PEF treatment only in 1st generation and EP- repeatedly exposed to pulse treatment
Summary
Pulsed electric field treatment has increased over the last few decades with successful translation from in vitro studies into different medical treatments like electrochemotherapy, irreversible electroporation for tumor and cardiac tissue ablation and gene electrotransfer for gene therapy and DNA vaccination. Pulsed electric field treatments are efficient but localized often requiring repeated applications to obtain results due to partial response and recurrence of disease. In IRE treatment targeted tissue is efficiently destroyed, the integrity of nearby tissue structures like vessels and nerves are preserved as well as extracellular matrix[12,13] This is why IRE is on its way to become the leading therapy for cardiac ablation[14,15,16]. Electrochemotherapy and IRE are efficient and cause complete or partial response of the treated tumors/tissue which leads to prolonged survival and significant pain reduction[12,31,32]
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