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Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

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 “environme...

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Autores principales: Parate, Dinesh, Kadir, Nurul Dinah, Celik, Cenk, Lee, Eng Hin, Hui, James H. P., Franco-Obregón, Alfredo, Yang, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998094/
https://www.ncbi.nlm.nih.gov/pubmed/32014064
http://dx.doi.org/10.1186/s13287-020-1566-5
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author Parate, Dinesh
Kadir, Nurul Dinah
Celik, Cenk
Lee, Eng Hin
Hui, James H. P.
Franco-Obregón, Alfredo
Yang, Zheng
author_facet Parate, Dinesh
Kadir, Nurul Dinah
Celik, Cenk
Lee, Eng Hin
Hui, James H. P.
Franco-Obregón, Alfredo
Yang, Zheng
author_sort Parate, Dinesh
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-020-1566-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-69980942020-02-05 Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration Parate, Dinesh Kadir, Nurul Dinah Celik, Cenk Lee, Eng Hin Hui, James H. P. Franco-Obregón, Alfredo Yang, Zheng Stem Cell Res Ther Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-020-1566-5) contains supplementary material, which is available to authorized users. BioMed Central 2020-02-03 /pmc/articles/PMC6998094/ /pubmed/32014064 http://dx.doi.org/10.1186/s13287-020-1566-5 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Parate, Dinesh
Kadir, Nurul Dinah
Celik, Cenk
Lee, Eng Hin
Hui, James H. P.
Franco-Obregón, Alfredo
Yang, Zheng
Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration
title Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration
title_full Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration
title_fullStr Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration
title_full_unstemmed Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration
title_short Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration
title_sort pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998094/
https://www.ncbi.nlm.nih.gov/pubmed/32014064
http://dx.doi.org/10.1186/s13287-020-1566-5
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