Author: Parate D1,2,3, Kadir ND3, Celik C3, Lee EH3,4, Hui JHP3,4, Franco-Obregón A5,6,7, Yang Z8,9
Affiliation: <sup>1</sup>Department of Surgery, National University of Singapore, Singapore, 119228, Singapore.
<sup>2</sup>Biolonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore, Singapore.
<sup>3</sup>Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore, 119288, Singapore.
<sup>4</sup>Tissue Engineering Program, Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117510, Singapore.
<sup>5</sup>Department of Surgery, National University of Singapore, Singapore, 119228, Singapore. suraf@nus.edu.sg.
<sup>6</sup>Biolonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore, Singapore. suraf@nus.edu.sg.
<sup>7</sup>Institute for Health Innovation & Technology, iHealthtech, National University of Singapore, Singapore, Singapore. suraf@nus.edu.sg.
<sup>8</sup>Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore, 119288, Singapore. dosyz@nus.edu.sg.
<sup>9</sup>Tissue Engineering Program, Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117510, Singapore. dosyz@nus.edu.sg.
Conference/Journal: Stem Cell Res Ther.
Date published: 2020 Feb 3
Other:
Volume ID: 11 , Issue ID: 1 , Pages: 46 , Special Notes: doi: 10.1186/s13287-020-1566-5. , Word Count: 318
BACKGROUND: The mesenchymal stem cell (MSC) secretome, via the combined actions of its plethora of biologically active factors, is capable of orchestrating the regenerative responses of numerous tissues by both eliciting and amplifying biological responses within recipient cells. MSCs are "environmentally responsive" to local micro-environmental cues and biophysical perturbations, influencing their differentiation as well as secretion of bioactive factors. We have previously shown that exposures of MSCs to pulsed electromagnetic fields (PEMFs) enhanced MSC chondrogenesis. Here, we investigate the influence of PEMF exposure over the paracrine activity of MSCs and its significance to cartilage regeneration.
METHODS: Conditioned medium (CM) was generated from MSCs subjected to either 3D or 2D culturing platforms, with or without PEMF exposure. The paracrine effects of CM over chondrocytes and MSC chondrogenesis, migration and proliferation, as well as the inflammatory status and induced apoptosis in chondrocytes and MSCs was assessed.
RESULTS: We show that benefits of magnetic field stimulation over MSC-derived chondrogenesis can be partly ascribed to its ability to modulate the MSC secretome. MSCs cultured on either 2D or 3D platforms displayed distinct magnetic sensitivities, whereby MSCs grown in 2D or 3D platforms responded most favorably to PEMF exposure at 2 mT and 3 mT amplitudes, respectively. Ten minutes of PEMF exposure was sufficient to substantially augment the chondrogenic potential of MSC-derived CM generated from either platform. Furthermore, PEMF-induced CM was capable of enhancing the migration of chondrocytes and MSCs as well as mitigating cellular inflammation and apoptosis.
CONCLUSIONS: The findings reported here demonstrate that PEMF stimulation is capable of modulating the paracrine function of MSCs for the enhancement and re-establishment of cartilage regeneration in states of cellular stress. The PEMF-induced modulation of the MSC-derived paracrine function for directed biological responses in recipient cells or tissues has broad clinical and practical ramifications with high translational value across numerous clinical applications.
KEYWORDS: Cartilage; Mesenchymal stem cells; Paracrine; Pulse electromagnetic fields
PMID: 32014064 DOI: 10.1186/s13287-020-1566-5