Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing

Delayed fracture healing and fracture non-unions impose an enormous burden on individuals and society. Successful healing requires tight communication between immune cells and bone cells. Macrophages can be found in all healing phases. Due to their high plasticity and long life span, they represent...

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Autores principales: Yangmengfan Chen, Maximilian M. Menger, Benedikt J. Braun, Sara Schweizer, Caren Linnemann, Karsten Falldorf, Michael Ronniger, Hongbo Wang, Tina Histing, Andreas K. Nussler, Sabrina Ehnert
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spelling oai:doaj.org-article:dcd8e185d0fb492ab3aaa5b14478927b2021-11-25T16:46:30ZModulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing10.3390/bioengineering81101672306-5354https://doaj.org/article/dcd8e185d0fb492ab3aaa5b14478927b2021-10-01T00:00:00Zhttps://www.mdpi.com/2306-5354/8/11/167https://doaj.org/toc/2306-5354Delayed fracture healing and fracture non-unions impose an enormous burden on individuals and society. Successful healing requires tight communication between immune cells and bone cells. Macrophages can be found in all healing phases. Due to their high plasticity and long life span, they represent good target cells for modulation. In the past, extremely low frequency pulsed electromagnet fields (ELF-PEMFs) have been shown to exert cell-specific effects depending on the field conditions. Thus, the aim was to identify the specific ELF-PEMFs able to modulate macrophage activity to indirectly promote mesenchymal stem/stromal cell (SCP-1 cells) function. After a blinded screening of 22 different ELF-PEMF, two fields (termed A and B) were further characterized as they diversely affected macrophage function. These two fields have similar fundamental frequencies (51.8 Hz and 52.3 Hz) but are emitted in different groups of pulses or rather send–pause intervals. Macrophages exposed to field A showed a pro-inflammatory function, represented by increased levels of phospho-Stat1 and CD86, the accumulation of ROS, and increased secretion of pro-inflammatory cytokines. In contrast, macrophages exposed to field B showed anti-inflammatory and pro-healing functions, represented by increased levels of Arginase I, increased secretion of anti-inflammatory cytokines, and growth factors are known to induce healing processes. The conditioned medium from macrophages exposed to both ELF-PEMFs favored the migration of SCP-1 cells, but the effect was stronger for field B. Furthermore, the conditioned medium from macrophages exposed to field B, but not to field A, stimulated the expression of extracellular matrix genes in SCP-1 cells, i.e., <i>COL1A1</i>, <i>FN1</i>, and <i>BGN</i>. In summary, our data show that specific ELF-PEMFs may affect immune cell function. Thus, knowing the specific ELF-PEMFs conditions and the underlying mechanisms bears great potential as an adjuvant treatment to modulate immune responses during pathologies, e.g., fracture healing.Yangmengfan ChenMaximilian M. MengerBenedikt J. BraunSara SchweizerCaren LinnemannKarsten FalldorfMichael RonnigerHongbo WangTina HistingAndreas K. NusslerSabrina EhnertMDPI AGarticleextremely low frequency pulsed electromagnetic fields (ELF-PEMFs)macrophagesmesenchymal stem/stromal cellsextracellular matrixfracture healingTechnologyTBiology (General)QH301-705.5ENBioengineering, Vol 8, Iss 167, p 167 (2021)
institution DOAJ
collection DOAJ
language EN
topic extremely low frequency pulsed electromagnetic fields (ELF-PEMFs)
macrophages
mesenchymal stem/stromal cells
extracellular matrix
fracture healing
Technology
T
Biology (General)
QH301-705.5
spellingShingle extremely low frequency pulsed electromagnetic fields (ELF-PEMFs)
macrophages
mesenchymal stem/stromal cells
extracellular matrix
fracture healing
Technology
T
Biology (General)
QH301-705.5
Yangmengfan Chen
Maximilian M. Menger
Benedikt J. Braun
Sara Schweizer
Caren Linnemann
Karsten Falldorf
Michael Ronniger
Hongbo Wang
Tina Histing
Andreas K. Nussler
Sabrina Ehnert
Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing
description Delayed fracture healing and fracture non-unions impose an enormous burden on individuals and society. Successful healing requires tight communication between immune cells and bone cells. Macrophages can be found in all healing phases. Due to their high plasticity and long life span, they represent good target cells for modulation. In the past, extremely low frequency pulsed electromagnet fields (ELF-PEMFs) have been shown to exert cell-specific effects depending on the field conditions. Thus, the aim was to identify the specific ELF-PEMFs able to modulate macrophage activity to indirectly promote mesenchymal stem/stromal cell (SCP-1 cells) function. After a blinded screening of 22 different ELF-PEMF, two fields (termed A and B) were further characterized as they diversely affected macrophage function. These two fields have similar fundamental frequencies (51.8 Hz and 52.3 Hz) but are emitted in different groups of pulses or rather send–pause intervals. Macrophages exposed to field A showed a pro-inflammatory function, represented by increased levels of phospho-Stat1 and CD86, the accumulation of ROS, and increased secretion of pro-inflammatory cytokines. In contrast, macrophages exposed to field B showed anti-inflammatory and pro-healing functions, represented by increased levels of Arginase I, increased secretion of anti-inflammatory cytokines, and growth factors are known to induce healing processes. The conditioned medium from macrophages exposed to both ELF-PEMFs favored the migration of SCP-1 cells, but the effect was stronger for field B. Furthermore, the conditioned medium from macrophages exposed to field B, but not to field A, stimulated the expression of extracellular matrix genes in SCP-1 cells, i.e., <i>COL1A1</i>, <i>FN1</i>, and <i>BGN</i>. In summary, our data show that specific ELF-PEMFs may affect immune cell function. Thus, knowing the specific ELF-PEMFs conditions and the underlying mechanisms bears great potential as an adjuvant treatment to modulate immune responses during pathologies, e.g., fracture healing.
format article
author Yangmengfan Chen
Maximilian M. Menger
Benedikt J. Braun
Sara Schweizer
Caren Linnemann
Karsten Falldorf
Michael Ronniger
Hongbo Wang
Tina Histing
Andreas K. Nussler
Sabrina Ehnert
author_facet Yangmengfan Chen
Maximilian M. Menger
Benedikt J. Braun
Sara Schweizer
Caren Linnemann
Karsten Falldorf
Michael Ronniger
Hongbo Wang
Tina Histing
Andreas K. Nussler
Sabrina Ehnert
author_sort Yangmengfan Chen
title Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing
title_short Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing
title_full Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing
title_fullStr Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing
title_full_unstemmed Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing
title_sort modulation of macrophage activity by pulsed electromagnetic fields in the context of fracture healing
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/dcd8e185d0fb492ab3aaa5b14478927b
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