Pulsed Electric Field Ablation of Esophageal Malignancies and Mitigating Damage to Smooth Muscle: An In Vitro Study
International Journal of Molecular Sciences
Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca2+ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them less vulnerable to electroporation. We infer that damage to SMC from nsPEF ablation of esophageal malignancies can be minimized by applying the electric field parallel to the predominant SMC orientation.
© 2023 by the authors.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Article states: The data presented in this study are available on request from the corresponding author.
Original Publication Citation
Gudvangen, E., Mangalanathan, U., Semenov, I., Kiester, A. S., Keppler, M. A., Ibey, B. L., Bixler, J. N., & Pakhomov, A. G. (2023). Pulsed electric field ablation of esophageal malignancies and mitigating damage to smooth muscle: An in vitro study. International Journal of Molecular Sciences, 24(3), 1-16, Article 2854. https://doi.org/10.3390/ijms24032854
Gudvangen, Emily; Mangalanathan, Uma; Semenov, Iurii; Kiester, Allen S.; Keppler, Mark A.; Ibey, Bennett L.; Bixler, Joel N.; and Pakhomov, Andrei G., "Pulsed Electric Field Ablation of Esophageal Malignancies and Mitigating Damage to Smooth Muscle: An In Vitro Study" (2023). Bioelectrics Publications. 350.
0000-0003-0126-5660 (Mangalanathan), 0000-0002-0302-1355 (Semenov), 0000-0003-3816-3860 (Pakhomov)