Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields.

Author: Parate D1, Franco-Obregón A2,3, Fröhlich J4,5, Beyer C5, Abbas AA6, Kamarul T6, Hui JHP7,8, Yang Z9,10
Affiliation:
1Department 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.
2Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, IE Kent Ridge Road, Singapore, 119228, Singapore. suraf@nus.edu.sg.
3BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, MD6, 14 medical Drive, #14-01, Singapore, 117599, Singapore. suraf@nus.edu.sg.
4Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, IE Kent Ridge Road, Singapore, 119228, Singapore.
5Institute for Electromagnetic Fields, Swiss Federal Institute of Technology (ETH), Rämistrasse 101, 8092, Zurich, Switzerland.
6Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, 50603, Malaysia.
7Department 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. james_hui@nuhs.edu.sg.
8Tissue Engineering Program, Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117510, Singapore. james_hui@nuhs.edu.sg.
9Department 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. lsiyz@nus.edu.sg.
10Tissue Engineering Program, Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117510, Singapore. lsiyz@nus.edu.sg.

Conference/Journal: Sci Rep.
Date published: 2017 Aug 25
Other: Volume ID: 7 , Issue ID: 1 , Pages: 9421 , Special Notes: doi: 10.1038/s41598-017-09892-w. , Word Count: 203


Pulse electromagnetic fields (PEMFs) have been shown to recruit calcium-signaling cascades common to chondrogenesis. Here we document the effects of specified PEMF parameters over mesenchymal stem cells (MSC) chondrogenic differentiation. MSCs undergoing chondrogenesis are preferentially responsive to an electromagnetic efficacy window defined by field amplitude, duration and frequency of exposure. Contrary to conventional practice of administering prolonged and repetitive exposures to PEMFs, optimal chondrogenic outcome is achieved in response to brief (10 minutes), low intensity (2 mT) exposure to 6 ms bursts of magnetic pulses, at 15 Hz, administered only once at the onset of chondrogenic induction. By contrast, repeated exposures diminished chondrogenic outcome and could be attributed to calcium entry after the initial induction. Transient receptor potential (TRP) channels appear to mediate these aspects of PEMF stimulation, serving as a conduit for extracellular calcium. Preventing calcium entry during the repeated PEMF exposure with the co-administration of EGTA or TRP channel antagonists precluded the inhibition of differentiation. This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. The demonstrated efficacy of our optimized PEMF regimens has clear clinical implications for future regenerative strategies for cartilage.

PMID: 28842627 DOI: 10.1038/s41598-017-09892-w

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