Magnetic Stimulation Drives Macrophage Polarization in Cell to–Cell Communication with IL-1β Primed Tendon Cells

Abstract

Inflammation is part of the natural healing response, but it has been simultaneously associated with tendon disorders, as persistent inflammatory events contribute to physiological changes that compromise tendon functions. The cellular interactions within a niche are extremely important for healing. While human tendon cells (hTDCs) are responsible for the maintenance of tendon matrix and turnover, macrophages regulate healing switching their functional phenotype to environmental stimuli. Thus, insights on the hTDCs and macrophages interactions can provide fundamental contributions on tendon repair mechanisms and on the inflammatory inputs in tendon disorders. We explored the crosstalk between macrophages and hTDCs using co-culture approaches in which hTDCs were previously stimulated with IL-1β. The potential modulatory effect of the pulsed electromagnetic field (PEMF) in macrophage-hTDCs communication was also investigated using the magnetic parameters identified in a previous work. The PEMF influences a macrophage pro-regenerative phenotype and favors the synthesis of anti-inflammatory mediators. These outcomes observed in cell contact co-cultures may be mediated by FAK signaling. The impact of the PEMF overcomes the effect of IL-1β-treated-hTDCs, supporting PEMF immunomodulatory actions on macrophages. This work highlights the relevance of intercellular communication in tendon healing and the beneficial role of the PEMF in guiding inflammatory responses toward regenerative strategies.

Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro

“…Different polymers including poly( -caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactide-co-glycolide) (PLGA) are FDA-approved polymers that have been widely applied for biomedical and in particular tendon applications [1,2,[4][5][6][7][8][9][10][11][12][13][14]. Although PLA and PCL are two biocompatible polymers, they are characterized by high hydrophobic properties that decreased cell adhesion due to the lack of cell recognition sites on their surfaces [9,15,16].…”

Repetitive Trans Spinal Magnetic Stimulation Improves Functional Recovery and Tissue Repair in Contusive and Penetrating Spinal Cord Injury Models in Rats

“…It has been also shown that macrophages instead of microglia are mainly implicated in secondary axonal dieback ( 28 . The immunomodulatory role played by magnetic stimulation (MS) on macrophages in culture has been already investigated ( 29 . It appears that MS can act on macrophages polarization.…”

Human tendon-derived cell sheets created by magnetic force-based tissue engineering hold tenogenic and immunomodulatory potential

“…From our previous studies, PEMF has shown a great impact in the inflammatory profile of IL-1β-hTDCs influencing the release and expression of cytokines [17,18,39]. Despite the fact that such works were performed in monolayer cultures and in the absence of MNPs, the combination of MNPs actuated by an external magnetic field could stimulates specific biochemical responses [48].…”

“…IL-1 is a proinflammatory cytokine released in inflammatory environments [14] and a well described marker of chronic inflammation [15,16]. From previous reports by our group [17,18] and others [19][20][21] exposure to low frequency (2 to 75Hz) and low strength (1.5 to 82mT) magnetic fields, was shown to modulate tendon cell response to inflammation stresses influencing the release and expression of cytokines [17,18]. Other works also showed the effectiveness of the combination of magnetic nanoparticles (MNPs) with magnetic field for pain control and enhanced functional recovery in the knee diseases and osteoarthritic lesions [22].…”