Calcium Signaling Hacking by MILD Electroporation: A Novel Approach for Bioelectronic Medicine

This is the authors' abstract. We don't add key points for this paper.

Electrical stimulation has expanded beyond excitable tissues, with bioelectronic medicine exploring new therapeutic avenues. We propose a novel paradigm: continuously repeated electroporation to induce controlled Ca 2+ influx and modulate cellular functions. Given the central role of Ca 2+ as a second messenger tightly regulated by homeostatic mechanisms, transient permeabilization via electric fields enables perturbation of intracellular Ca 2+ dynamics, influencing processes such as proliferation, differentiation, metabolism, and cell death. We define “MILD electroporation” as a process involving prolonged or repetitive mild membrane permeabilization induced by electric fields that facilitates calcium entry without causing direct cell death. At 5 th World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine, and Food & Environmental Technologies, we presented in vitro evidence showing that specific electric field waveforms elicit Ca 2+ oscillations in stem cells, modulating gene expression and promoting proliferation. We also presented preliminary results suggesting that burst-modulated alternating fields may slow cancer cell proliferation.