Brief exposure to directionally-specific pulsed electromagnetic fields stimulates extracellular vesicle release and is antagonized by streptomycin: A potential regenerative medicine and food industry paradigm

Craig Jun Kit Wong; Yee Kit Tai; Jasmine Lye Yee Yap; Charlene Hui Hua Fong; Larry Sai Weng Loo; Marek Kukumberg; Jürg Fröhlich; Sitong Zhang; Jing Ze Li; Jiong-Wei Wang; Abdul Jalil Rufaihah; Alfredo Franco-Obregón

doi:10.1016/j.biomaterials.2022.121658

Brief exposure to directionally-specific pulsed electromagnetic fields stimulates extracellular vesicle release and is antagonized by streptomycin: A potential regenerative medicine and food industry paradigm

Biomaterials. 2022 Aug:287:121658. doi: 10.1016/j.biomaterials.2022.121658. Epub 2022 Jul 6.

Affiliations

¹ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Institute of Health Technology and Innovation (iHealthtech), National University of Singapore, 117599, Singapore; Biolonic Currents Electromagnetic Pulsing Systems Laboratory (BICEPS), National University of Singapore, 117599, Singapore.
² Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Institute of Health Technology and Innovation (iHealthtech), National University of Singapore, 117599, Singapore; Biolonic Currents Electromagnetic Pulsing Systems Laboratory (BICEPS), National University of Singapore, 117599, Singapore. Electronic address: surtaiyk@nus.edu.sg.
³ Institute of Bioengineering and Bioimaging, A*STAR, The Nanos, #06-01, 31 Biopolis Way, 138669, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593, Singapore.
⁴ Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore.
⁵ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Fields at Work GmbH, Zurich 8032, Switzerland.
⁶ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁷ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore.
⁸ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593, Singapore; Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cardiovascular Research Institute, National University Heart Centre Singapore, Singapore, 119074, Singapore.
⁹ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; School of Applied Sciences, Temasek Polytechnic, 529757, Singapore.
¹⁰ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Institute of Health Technology and Innovation (iHealthtech), National University of Singapore, 117599, Singapore; Biolonic Currents Electromagnetic Pulsing Systems Laboratory (BICEPS), National University of Singapore, 117599, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593, Singapore; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore. Electronic address: suraf@nus.edu.sg.

PMID: 35841726
DOI: 10.1016/j.biomaterials.2022.121658

Abstract

Pulsing electromagnetic fields (PEMFs) have been shown to promote in vitro and in vivo myogeneses via mitohormetic survival adaptations of which secretome activation is a key component. A single 10-min exposure of donor myoblast cultures to 1.5 mT amplitude PEMFs produced a conditioned media (pCM) capable of enhancing the myogenesis of recipient cultures to a similar degree as direct magnetic exposure. Downwardly-directed magnetic fields produced greater secretome responses than upwardly-directed fields in adherent and fluid-suspended myoblasts. The suspension paradigm allowed for the rapid concentrating of secreted factors, particularly of extracellular vesicles. The brief conditioning of basal media from magnetically-stimulated myoblasts was capable of conferring myoblast survival to a greater degree than basal media supplemented with fetal bovine serum (5%). Downward-directed magnetic fields, applied directly to cells or in the form of pCM, upregulated the protein expression of TRPC channels, markers for cell cycle progression and myogenesis. Direct magnetic exposure produced mild oxidative stress, whereas pCM provision did not, providing a survival advantage on recipient cells. Streptomycin, a TRP channel antagonist, precluded the production of a myogenic pCM. We present a methodology employing a brief and non-invasive PEMF-exposure paradigm to effectively stimulate secretome production and release for commercial or clinical exploitation.

Keywords: Cell-based meat; Conditioned media; Extracellular vesicles; Myokines; Streptomycin; TRPC1.