Pulsed Electromagnetic Fields Exposure Research Articles

Effect of hydroxyapatite and pulsed electromagnetic field on osteogenic differentiation of human stem cells seeded onto 3D‐printed polycaprolactone scaffolds for future bone graft transplantation

AbstractBone graft transplantation is a risky procedure mainly due to postoperative complications. Tissue engineering is an alternative to regenerating bone tissue by seeding mesenchymal stem cells into 3D scaffolds by osteoinductive signaling. Poly(ε‐caprolactone) (PCL) is one of the most used biopolymers for fabricating scaffolds for bone tissue engineering. PCL is enriched with hydroxyapatite (HA) to promote the production of the bone‐mineralized matrix. Moreover, the application of pulsed electromagnetic fields (PEMFs) on scaffolds loaded with HA can significantly benefit collagen and HA networks favoring the interaction between organic and mineral phases of bones. In this context, we investigated, for the first time, the effect exerted by a PEMF exposure on the osteogenic differentiation of human adipose stem cells (hASCs) seeded onto 3D printed PCL‐HA scaffolds and cultured in growth and osteogenic medium (OM). After 21 days of culture, the results showed excellent colonization of scaffolds and the deposition of extracellular matrix (ECM) secreted by hASCs. Immunofluorescence staining confirmed the deposition of collagen type I and osteopontin both on scaffolds. Gene expression analysis indicated that both HA crystal and PEMF treatment were able to trigger osteogenic differentiation, as documented by the increase of osteogenic markers. These results suggest that HA, osteogenic factors, and PEMFs converge on the same signaling pathways as there are no additive effects and no change in protein synthesis between scaffolds with HA or treated with PEMFs for cells cultured in OM. The proposed study lays the foundations for exploring new approaches in bone graft transplantation.

Metabolomics comparison of metabolites and functional pathways in the SH-SY5Y cell model of Parkinson's disease under PEMF exposure

ObjectivePEMF is an emerging technique in the treatment of Parkinson's disease (PD) due to its potential improvement of movement speed. The aim of this study was to investigate the metabolic profiles of pulsed electromagnetic fields (PEMFs) in an SH-SY5Y cell model of PD. MethodsThe SH-SY5Y cell model of PD was induced by 1-methyl-4-phenylpyridinium (MPP+). Liquid chromatography mass spectrometry (LC‒MS)-based untargeted metabolomics was performed to examine changes in the PD cell model with or without PEMF exposure. We conducted KEGG pathway enrichment analysis to explore the potentially related pathways of the differentially expressed metabolites. ResultsA total of 275 metabolites were annotated, and 27 significantly different metabolites were found between the PEMF treatment and control groups (VIP >1, P < 0.05), mainly including 4 amino acids and peptides, 4 fatty acid esters, 2 glycerophosphoethanolamines, 2 ceramides and 2 monoradylglycerols; among them, 12 metabolites were upregulated, and 15 were downregulated. The increased expression levels of glutamine, adenosine monophosphate and taurine were highly associated with PEMF stimulation in the PD model. The enrichment results of differentially abundant metabolite functional pathways showed that biological processes such as the mTOR signaling pathway, PI3K-Akt signaling pathway, and cAMP signaling pathway were significantly affected. ConclusionPEMFs affected glutamine, adenosine monophosphate and taurine as well as their functional pathways in an in vitro model of PD. Further functional studies regarding the biological effect of these changes are required to evaluate the clinical efficacy and safety of PEMF treatment in PD.

Inductively Coupled Electrical Stimulation - Part 6: Duration of PEMF-induced enhanced seed germination

The objective of this study was to directly answer the practical question: how long lasting are the observed effects of pulsed electro-magnetic fields (PEMF) on seed germination? Earlier studies have shown that the effect of PEMF treatment on seed germination can be positive, neutral, or negative, exhibiting a tri-phasic inverse hormesis behavior as a function of total PEMF dosage during a single treatment session. This allows an optimal dosage range to be determined for maximum progerminative effect. Dosages in this range were found in earlier studies to increase the germination rate of pepper seeds to ~ 85%, from the baseline germination rate of ~56%, amounting to an increased germination rate of ~150% of baseline. &#x0D; One major practical consideration of this observation is whether the PEMF treatment is durable enough to allow central processing and long-term storage of the seeds for later use, or whether seeds treated by PEMF need to be planted shortly after treatment due to rapid loss of effect over time. If the latter, what is the allowable time between PEMF treatment and planting? In addition to their practical value, these observations will have considerable theoretical value as well. As the underlying biophysical mechanism of PEMF remains to be elucidated, quantitative assessments of the durability of the effect of PEMF treatment will give important clues as to the potential mechanisms involved; for example, whether they involve the activation of enzyme systems that remain activated or taper off, whether they initiate the release or activation of substances in reserve in the germ that are exhausted upon a single use, whether multiple mechanisms are involved as evidenced by multi-phasic decay over time, or whether the progerminative effect can be repeated more than one time in any given seed.&#x0D; For this study, the duration of the progerminative effect was measured by applying a previously-determined “optimal” dose of PEMF to pepper seeds, then storing the seeds in their original paper envelopes in a darkened room at 50% RH and room temperature for a period of up to one year post-treatment before planting, and determination of germination rate at two weeks (14 days). Finally, we study whether the lost progerminative effect can be recovered in stored seeds by reapplication of PEMF at the same dose immediately before planting. &#x0D; Our findings were that (1) the progerminative effect lasted only about 2 days after PEMF exposure, then returned about half way back to baseline and began a slow decline thereafter, but remained at approximately half-way, never returning to baseline even for periods of storage as long as 1 year, (2) a second application of PEMF restored almost all of the progerminative effect even after storage periods of up to one year. Storage periods longer than 1 year were not studied.&#x0D; These results add to the discussion of the mechanisms of PEMF across the span of complex organisms by suggesting the involvement of multiple mechanisms, some durable while others are semi-permanent.

Brief, weekly magnetic muscle therapy improves mobility and lean body mass in older adults: a Southeast Asia community case study

Brief (10 min) weekly exposure to low energy pulsed electromagnetic fields (PEMFs) has been shown to improve human muscle mitochondrial bioenergetics and attenuate systemic lipotoxicity following anterior cruciate ligament surgical reconstruction. Here we present data generated from 101 participants, 62% female, aged 38-91 years, recruited from the QuantumTx Demo Centre in Singapore, wherein 87% of participants (n = 88) presented with pre-existing mobility dysfunction and 13% (n = 13) were healthy volunteers. Participants were recruited if: (i) not pregnant; (ii) above 35 years of age and; (iii) without surgical implants. All participants completed mobility testing, pre- and post- PEMF intervention for 12 weeks, whereas bioelectrical impedance analysis was conducted in a subgroup of 42 and 33 participants at weeks 4 and 8, respectively. Weekly PEMF exposure was associated with significant improvements in mobility (Timed Up and Go, 5 times Sit-to-Stand, and 4m Normal Gait Speed) and body composition (increased skeletal muscle mass and reduced total and visceral fat mass), particularly in the older participants. Perception of pain was also significantly reduced. PEMF therapy may provide a manner to counteract age-associated mobility and metabolic disruptions and merits future investigation in randomized controlled trials to elucidate its clinical benefits in the frail and older adult populations.

Low frequency pulsed electromagnetic fields exposure alleviate the abnormal subchondral bone remodeling at the early stage of temporomandibular joint osteoarthritis

BackgroundTemporomandibular joint osteoarthritis (TMJOA) is characterized by abnormal subchondral bone remodeling and cartilage degeneration. As a non-invasive biophysical technology, pulsed electromagnetic field (PEMF) treatment has been proven to be efficient in promoting osteogenesis. However, the potential bone protective effect and mechanism of PEMF on abnormal subchondral bone remodeling in TMJOA are unknown.MethodsUnilateral anterior crossbite (UAC) was used to create TMJOA model in rats, and 17β-estradiol (E2) were injected daily to mimic patients with high-physiological levels of estrogen. Mouse osteoblast-like MC3T3-E1 cells treated with recombinant murine IL-1β was used to establish inflammatory environment in vitro. The treatment group were subjected to PEMF (2.0mT, 15 Hz, 2 h/d). Micro-CT scanning, histological staining, real-time PCR and western blotting assays were preformed to observe the changes in the subchondral bone.ResultsAbnormal resorption of subchondral bone induced by UAC, characterized by decreased bone mineral density, increased osteoclast activity and expression of osteoclast-related factors (RANKL) and down-regulated expression of osteogenesis-related factors (OPG, ALP, Runx2 and OCN) at the early stage, could be reversed by PEMF exposure, which was similar to the effect of estrogen. In addition, PEMF exposure and E2 supplement may have a synergistic effect to some extent. Moreover, PEMF exposure could promote the ALP activity and osteogenic mineralization ability of MC3T3-E1 cells. PEMF promoted the expression of factors related to Wnt/β-Catenin signal pathway both in vivo and in vitro.ConclusionsAppropriate PEMF exposure have a protective effect on subchondral bone in TMJOA at early stage, in which canonical Wnt/β-Catenin pathway may be involved. PEMF may be a promising biophysical approach for early intervention of TMJOA in clinic.

Effect of pulsed electromagnetic field as an intervention for patients with quadriceps weakness after anterior cruciate ligament reconstruction: a double-blinded, randomized-controlled trial

BackgroundThe ultimate goal of anterior cruciate ligament reconstructions (ACLR) is to fulfil the return-to-play (RTP) criteria. Quadriceps muscle strength is one of the key determinants for a patient’s successful return-to-play after ACLR. Quadriceps muscle atrophy can persist beyond the completion of the rehabilitation program in almost half the patients and the reason behind this is still unknown. There are emerging evidences showing that pulsed electromagnetic field (PEMF) can modulate mitochondrial activities for muscle gain. PEMF exposure on top of regular exercise training may promote muscle regeneration and tissue healing.MethodsThis is a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment during the postoperative period on quadriceps muscle strength in ACL injured patient. Adult patients (aged 18–30) with a unilateral ACL injury, total quadriceps muscle volume is equal or more than 7% deficit on involved leg compared with uninvolved leg, sporting injury with a Tegner score of 7+, and both knees without a history of injury/prior surgery will be recruited. To estimate the improvement of patients, isokinetic muscle assessment, ultrasound imaging and MRI for quadriceps muscle thickness, self-reported outcomes with questionnaires, KT-1000 for knee laxity and biomechanical analysis, and Xtreme CT for bone mineral density will be performed. To investigate the mechanism of PEMF therapy on increasing quadriceps strength, samples of blood serum will be drawn before and after intervention.DiscussionThis is the first trial evaluating the effects of PEMF on quadriceps muscle recovery after ACLR. The proposed study addresses a huge research gap by evaluating practical use of PEMF as part of rehabilitation. The proposed study will provide much needed scientific support in the use of this noninvasive treatment modality to facilitate recovery of quadriceps strength after PEMF.Trial registrationClinicalTrials.gov NCT05184023. Registered on 5 January 2022

Low-frequency pulsed electromagnetic fields promote osteoblast mineralization and maturation of rats through the PC2/sAC/PKA/CREB signaling pathway

To explore whether the effect of low-frequency pulsed electromagnetic fields (PEMFs) in promoting osteoblast mineralization and maturation is related to the primary cilia, polycystin2 (PC2) and sAC/PKA/CREB signaling pathway. We detected the expression levels of PC2, sAC, PKA, CREB and their phosphorylated proteins in primary rat calvarial osteoblasts exposed to 50 Hz 0.6 mT PEMFs for 0, 5, 15, 30, 60, 90, and 120 min. We blocked PC2 function with amiloride hydrochloride and detected the changes in the activity of sAC/PKA/CREB signal pathway and the mineralization and maturation of the osteoblasts. These examinations were repeated in the osteoblasts after specific knockdown of PC2 via RNA interference and were the co-localization of PC2, sAC, PKA, CREB and their phosphorylated proteins with the primary cilia were using immunofluorescence staining. The expressions of PC2 and the signaling proteins of sAC/PKA/CREB pathway were detected after inhibition of primary ciliation by RNA interference. The expression levels of PC2, sAC, p-PKA and p- CREB were significantly increased in the osteoblasts after exposure to PEMFs for different time lengths (P < 0.01). Blocking PC2 function or PC2 knockdown in the osteoblasts resulted in failure of sAC/PKA/CREB signaling pathway activation and arrest of osteoblast mineralization and maturation. PC2, sAC, p-PKA and p-CREB were localized to the entire primary cilia or its roots, but PKA and CREB were not detected in the primary cilia. After interference of the primary cilia, PEMFs exposure no longer caused increase of PC2 expression and failed to activate the sAC/PKA/CREB signaling pathway or promote osteoblast mineralization and maturation. PC2, located on the surface of the primary cilia of osteoblasts, can perceive and transmit the physical signals from PEMFs and promote the mineralization and maturation of osteoblasts by activating the PC2/ sAC/PKA/CREB signaling pathway.

Pulsed Electromagnetic Fields Protect Against Brain Ischemia by Modulating the Astrocytic Cholinergic Anti-inflammatory Pathway.

Neuroinflammation is one of the most important pathological processes following brain ischemia. Pulsed electromagnetic fields (PEMFs) protect against brain ischemia, but their role in regulating neuroinflammation remains unclear. In the present study, we investigated the biological effects of PEMF exposure on brain ischemia-induced neuroinflammation through the astrocytic cholinergic anti-inflammatory pathway. PEMF exposure reduced the activation of astrocytes and neuroinflammation following brain ischemia by directly modulating astrocytic injury and inflammatory cytokine release. Inhibition of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) by a specific antagonist reversed the regulatory effects of PEMF on astrocytes. Furthermore, negative regulation of signal transducer and activator of transcription 3 (STAT3) by α7nAChR was found to be an important downstream mechanism through which PEMF regulates astrocyte-related neuroinflammation. PEMF suppressed STAT3 phosphorylation and nuclear translocation by activating α7nAChR. These results demonstrate that PEMF exerts anti-inflammatory effects in the context of brain ischemia by modulating astrocytic α7nAChR/STAT3 signaling.

Magnetic field therapy enhances muscle mitochondrial bioenergetics and attenuates systemic ceramide levels following ACL reconstruction: Southeast Asian randomized-controlled pilot trial.

BackgroundMetabolic disruption commonly follows Anterior Cruciate Ligament Reconstruction (ACLR) surgery. Brief exposure to low amplitude and frequency pulsed electromagnetic fields (PEMFs) has been shown to promote in vitro and in vivo murine myogeneses via the activation of a calcium–mitochondrial axis conferring systemic metabolic adaptations. This randomized-controlled pilot trial sought to detect local changes in muscle structure and function using MRI, and systemic changes in metabolism using plasma biomarker analyses resulting from ACLR, with or without accompanying PEMF therapy.Methods20 patients requiring ACLR were randomized into two groups either undergoing PEMF or sham exposure for 16 weeks following surgery. The operated thighs of 10 patients were exposed weekly to PEMFs (1 ​mT for 10 ​min) for 4 months following surgery. Another 10 patients were subjected to sham exposure and served as controls to allow assessment of the metabolic repercussions of ACLR and PEMF therapy. Blood samples were collected prior to surgery and at 16 weeks for plasma analyses. Magnetic resonance data were acquired at 1 and 16 weeks post-surgery using a Siemens 3T Tim Trio system. Phosphorus (31P) Magnetic Resonance Spectroscopy (MRS) was utilized to monitor changes in high-energy phosphate metabolism (inorganic phosphate (Pi), adenosine triphosphate (ATP) and phosphocreatine (PCr)) as well as markers of membrane synthesis and breakdown (phosphomonoesters (PME) and phosphodiester (PDE)). Quantitative Magnetization Transfer (qMT) imaging was used to elucidate changes in the underlying tissue structure, with T1-weighted and 2-point Dixon imaging used to calculate muscle volumes and muscle fat content.ResultsImprovements in markers of high-energy phosphate metabolism including reductions in ΔPi/ATP, Pi/PCr and (Pi ​+ ​PCr)/ATP, and membrane kinetics, including reductions in PDE/ATP were detected in the PEMF-treated cohort relative to the control cohort at study termination. These were associated with reductions in the plasma levels of certain ceramides and lysophosphatidylcholine species. The plasma levels of biomarkers predictive of muscle regeneration and degeneration, including osteopontin and TNNT1, respectively, were improved, whilst changes in follistatin failed to achieve statistical significance. Liquid chromatography with tandem mass spectrometry revealed reductions in small molecule biomarkers of metabolic disruption, including cysteine, homocysteine, and methionine in the PEMF-treated cohort relative to the control cohort at study termination. Differences in measurements of force, muscle and fat volumes did not achieve statistical significance between the cohorts after 16 weeks post-ACLR.ConclusionThe detected changes suggest improvements in systemic metabolism in the post-surgical PEMF-treated cohort that accords with previous preclinical murine studies. PEMF-based therapies may potentially serve as a manner to ameliorate post-surgery metabolic disruptions and warrant future examination in more adequately powered clinical trials.The Translational Potential of this ArticleSome degree of physical immobilisation must inevitably follow orthopaedic surgical intervention. The clinical paradox of such a scenario is that the regenerative potential of the muscle mitochondrial pool is silenced. The unmet need was hence a manner to maintain mitochondrial activation when movement is restricted and without producing potentially damaging mechanical stress. PEMF-based therapies may satisfy the requirement of non-invasively activating the requisite mitochondrial respiration when mobility is restricted for improved metabolic and regenerative recovery.

Pulsed electromagnetic fields inhibit mandibular bone deterioration depending on the Wnt3a/β-catenin signaling activation in type 2 diabetic db/db mice

Type 2 diabetes mellitus (T2DM) patients have compromised mandibular bone architecture/quality, which markedly increase the risks of tooth loosening, tooth loss, and failure of dental implantation. However, it remains lacks effective and safe countermeasures against T2DM-related mandibular bone deterioration. Herein, we studied the effects of pulsed electromagnetic fields (PEMF) on mandibular bone microstructure/quality and relevant regulatory mechanisms in T2DM db/db mice. PEMF exposure (20 Gs, 15 Hz) for 12 weeks preserved trabecular bone architecture, increased cortical bone thickness, improved material properties and stimulated bone anabolism in mandibles of db/db mice. PEMF also upregulated the expression of canonical Wnt3a ligand (but not Wnt1 or Wnt5a) and its downstream β-catenin. PEMF improved the viability and differentiation of primary osteoblasts isolated from the db/db mouse mandible, and stimulated the specific activation of Wnt3a/β-catenin signaling. These positive effects of PEMF on mandibular osteoblasts of db/db mice were almost totally abolished after Wnt3a silencing in vitro, which were equivalent to the effects following blockade of canonical Wnt signaling using the broad-spectrum antagonist DKK1. Injection with Wnt3a siRNA abrogated the therapeutic effects of PEMF on mandibular bone quantity/quality and bone anabolism in db/db mice. Our study indicates that PEMF might become a non-invasive and safe treatment alternative resisting mandibular bone deterioration in T2DM patients, which is helpful for protecting teeth from loosening/loss and securing the dental implant stability.

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach.

Chemotherapy is the mainstream treatment modality for invasive breast cancer. Unfortunately, chemotherapy-associated adverse events can result in early termination of treatment. Paradoxical effects of chemotherapy are also sometimes observed, whereby prolonged exposure to high doses of chemotherapeutic agents results in malignant states resistant to chemotherapy. In this study, potential synergism between doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapy was investigated in: 1) MCF-7 and MDA-MB-231 cells in vitro; 2) MCF-7 tumors implanted onto a chicken chorioallantoic membrane (CAM) and; 3) human patient-derived and MCF-7 and MDA-MB-231 breast cancer xenografts implanted into NOD-SCID gamma (NSG) mice. In vivo, synergism was observed in patient-derived and breast cancer cell line xenograft mouse models, wherein PEMF exposure and DOX administration individually reduced tumor size and increased apoptosis and could be augmented by combined treatments. In the CAM xenograft model, DOX and PEMF exposure also synergistically reduced tumor size as well as reduced Transient Receptor Potential Canonical 1 (TRPC1) channel expression. In vitro, PEMF exposure alone impaired the survival of MCF-7 and MDA-MB-231 cells, but not that of non-malignant MCF10A breast cells; the selective vulnerability of breast cancer cells to PEMF exposure was corroborated in human tumor biopsy samples. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas TRPC1 genetic silencing reduced sensitivity to both DOX and PEMF treatments and mitigated proliferation. Chronic exposure to DOX depressed TRPC1 expression, proliferation, and responses to both PEMF exposure and DOX in a manner that was reversible upon removal of DOX. TRPC1 channel overexpression and silencing positively correlated with markers of epithelial-mesenchymal transition (EMT), including SLUG, SNAIL, VIMENTIN, and E-CADHERIN, indicating increased and decreased EMT, respectively. Finally, PEMF exposure was shown to attenuate the invasiveness of MCF-7 cells in correlation with TRPC1 expression. We thus demonstrate that the expression levels of TRPC1 consistently predicted breast cancer sensitivity to DOX and PEMF interventions and positively correlated to EMT status, providing an initial rationale for the use of PEMF-based therapies as an adjuvant to DOX chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.

Pulsed electromagnetic field alleviates synovitis and inhibits the NLRP3/Caspase-1/GSDMD signaling pathway in osteoarthritis rats

ABSTRACT Low-grade inflammation is a key mediator of the pathogenesis of Osteoarthritis (OA). Pulsed electromagnetic field (PEMF) can improve the symptoms of OA and potentially acts as an anti-inflammatory. The aim of this study was to investigate the effect of the PEMF on OA and its relationship with the NLRP3/Caspase-1/GSDMD signaling pathway.18 Three-month-old Sprague-Dawley (SD) rats were randomly divided into three groups (n = 6 per group): 1) OA group, 2) OA+PEMF group (OA with PEMF exposure), 3) Control group (sham operation with placebo PEMF). Rats in the OA and OA+PEMF groups were subjected to bilateral anterior cruciate ligament transection and ovariectomy. PEMF scheme: Pulse waveform, 3.82 mT, 8 Hz, 40 min/day, 5 days a week, for 12 weeks. The expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and MMP-13 were detected by qRT-PCR and Western blot. The pathological structures of OA were monitored with Safranin O/fast green staining and hematoxylin eosin staining. Our results showed that PEMF alleviated the degree of inflammation and degeneration of cartilage in rats with OA, based on the histopathological changes and decline of the expression of IL-1β and MMP-13. Moreover, the over-expression of NLRP3, Caspase-1, and GSDMD in the cartilage of the OA rats decreased after PEMF treatment. These results suggested that PEMF could be a highly promising noninvasive strategy to slow down the progression of OA and inhibition of the NLRP3/Caspase-1/GSDMD signaling pathway might be involved in the beneficial effect of PEMF.

Study of osteogenic potential of electrospun PCL incorporated by dendrimerized superparamagnetic nanoparticles as a bone tissue engineering scaffold

AbstractNanotechnology plays a promising role in biomedical applications, particularly tissue engineering. Recently, the application of magnetic scaffolds and pulsed electromagnetic field (PEMF) exposure has been considered in bone tissue regeneration. In this study, 3rd generation dendrimer‐modified superparamagnetic iron oxide nanoparticles (G3‐SPIONs) are synthesized and characterized. Magnetic polycaprolactone (PCL) nanofibers are prepared by incorporating G3‐SPIONs within the electrospinning process, and physicochemical characteristics, as well as cytocompatibility and cell attachment, are assessed. Eventually, the osteogenic differentiation ability of adipocyte‐derived mesenchymal stem cells (ADMSCs) cultured on the magnetic scaffold with and without PEMF exposure was investigated by measurement of alkaline phosphatase (ALP) activity and calcium content. The expression of specific bone markers was studied using the real‐time PCR method. According to the results, G3‐SPIONs with mean size and zeta potential of 17.95 ± 3.57 nm and 22.7 mV, respectively, shows high‐saturation magnetization (57.75 emu/g). Adding G3‐SPIONs to PCL significantly decreases nanofibers size to 495 ± 144 nm and improves cell attachment and growth. The ADMSCs cultured on the G3‐SPION‐PCL scaffold in the presence of osteogenic media (OM) and exposure to PEMF expressed the highest Osteocalcin and Runx2 and showed higher calcium content as well as ALP activity. It can be concluded that the synthesized G3‐SPION incorporated PCL nanofibers serve as a promising magnetic scaffold for bone regeneration. Also, utilizing the magnetic scaffold in the presence of OM and PEMF provides a synergistic effect toward osteogenic differentiation of ADMSCs.

Pulsed Electromagnetic Field Attenuates Osteoarthritis Progression in a Murine Destabilization-Induced Model through Inhibition of TNF-α and IL-6 Signaling.

To investigate the anti-inflammatory effects and mechanisms of pulsed electromagnetic field (PEMF) in the treatment of osteoarthritis (OA) in the destabilization of the medial meniscus (DMM) mice. Ten-week-old male wild-type (WT), interleukin (IL)-6-/- and tumor necrosis factor (TNF)-α-/- mice undergoing DMM surgery were randomly divided into 2 groups (n = 10 each): mice with PEMF exposure and mice with sham PEMF exposure. PEMF (75 Hz, 3.8 mT, 1 h/day) or sham PEMF was applied for 4 weeks. Pain behavior of mice, histological assessment of cartilage and synovium, micro-CT (computed tomography) analysis of bone, real-time polymerase chain reaction, and immunohistochemical staining of cartilage were performed. After DMM surgery, PEMF had a beneficial effect on pain, cartilage degeneration, synovitis, and trabecular bone microarchitecture in WT mice; these protective effects were reduced in IL-6-/- and TNF-α-/- mice. In addition, PEMF downregulated IL-6 and TNF-α expression in cartilage. PEMF also ameliorated cartilage matrix, chondrocyte apoptosis, and autophagy, while deletion of IL-6 or TNF-α suppressed the effects. PEMF attenuates structural and functional progression of OA through inhibition of TNF-α and IL-6 signaling. The protective effects of PEMF on chondrocyte apoptosis and autophagy are regulated by TNF-α and IL-6 signaling.

Effect of Pulse Electromagnetic Field Exposure on the Expression of Lipo Protein Lipase (LPL) on the Differentiation of Mesenchymal Stem Cell

Pulsed electromagnetic fields (PEMFs) have an important role in cell differentiation. Previous study reported that PEMFs had positive and negative effect towards cell differentiation that depends on their frequencies applied to the cells. Human adipose-derived stem cells (ASCs) are mesenchymal stem cells that have an ability to differentiate into several types of cell including adipocytes, chondrocytes and osteocytes. This study aimed to evaluate the effect of human ASCs towards their adipogenic differentiation during PEMFs exposure. Human ASCs were isolated from adipose tissue. The cells then cultured in specific medium of adipocyte that induced ASCs differentiation along with PEMFs exposure. The maximum magnetic field used is 2 mT with a frequency of 75 Hz. To confirm the effect of PEMFs exposure towards adipogenic differentiation, mRNA expression of lipo protein lipase (LPL) was measured in mRNA expression level. The results showed that ASCs cultured on adipogenic differentiation without PEMFs exposure gradually increased LPL expression until day 14 of observation, while ASCs with PEMFs exposure significantly decreased LPL expression from day 2 to day 14. Based on the results, we concluded that PEMFs exposure can inhibit LPL expression that suppressed adipogenic differentiation.

Effects of Pulsed Electromagnetic Field Therapy at Different Frequencies on Bone Mass and Microarchitecture in Osteoporotic Mice.

A pulsed electromagnetic field (PEMF) can promote osteogenesis. However, studies have shown variation in the signal characteristics in terms of waveform type, intensity, frequency, and treatment duration. Among the factors that affect electromagnetic fields, frequency plays a major role. However, few studies have investigated the effects of PEMF at different frequencies in osteoporotic mice. Therefore, our objective was to determine the effect of PEMF frequency in osteoporotic mice. Forty 3-month-old female mice were randomly divided into the following five groups: sham, OVX, and OVX followed by 1.6-mT PEMF exposure groups (8 Hz, 50 Hz, and 75 Hz, 1.6 mT). The PEMF was applied for 1 h/day, 7 days/week, for 4 weeks. After 4 weeks, the micro-computed tomography showed that PEMF with (50and 75 Hz) ameliorated the deterioration of bone microarchitecture. Improvements in the bone histological analysis were identified for PEMF with 50and 75 Hz groups compared with the ovariectomy (OVX) controls. Osteoclast numbers were decreased in PEMF with (50 and75 Hz). Moreover, the real-time PCR demonstrated PEMF with (50 and75 Hz) significantly promoted the expression of the osteoblast-related genes (ALP, OCN, Runx2), and increased the serum PINP. PEMF with (50 and75 Hz) exerted significant inhibitory effects on the osteoclast-related mRNA expression (CTSK, NFATc1, TRAP) and bone resorption markers CTX-I and IL-1β. Taken together, our results showed that PEMF at 50and 75 Hz with 1.6 mT significantly ameliorate the deterioration of bone microarchitecture in OVX mice. The inhibitory effect of PEMF may be associated with IL-1β inhibition. © 2021 Bioelectromagnetics Society.

Pulsed electromagnetic fields synergize with graphene to enhance dental pulp stem cell-derived neurogenesis by selectively targeting TRPC1 channels

Conventional root canal treatment replaces the infected pulp with defined materials. Alternative cell-based tissue engineering strategies aim to regenerate a fully functional pulp within the root canal. Despite recent advances in this area, however, the regeneration of an innervated pulp remains a major challenge in the field. Both graphene (2DG) and pulsed electromagnetic fields (PEMFs) independently have been shown to promote diverse cellular developmental programs. The present study showed that 2DG promoted the neurogenic induction of human dental pulp stem cells (hDPSCs) by upregulating and accelerating the expression of mature neuronal markers. Notably, 2DG induced the highest expression of transient receptor potential canonical cation channel type 1 (TRPC1) during early neurogenesis. As brief PEMF exposure promotes in vitro differentiation by activating a TRPC1-mitochondrial axis, an opportunity to combine 2DG with developmentally targeted PEMF exposure for synergistic effects was realizable. Neurogenic gene expression, neurotransmitter release, and reactive oxygen species (ROS) production were greatly enhanced by a brief (10 min) and low amplitude (2 mT) PEMF exposure timed to coincide with the highest TRPC1 expression from hDPSCs on 2DG. In contrast, hDPSCs on glass were less responsive to PEMF exposure. The capacity of PEMFs to promote neurogenesis was precluded by the administration of penicillin/streptomycin, mirroring previous studies demonstrating that aminoglycoside antibiotics block TRPC1-mediated calcium entry and verifying the contribution of TRPC1 in this form of magnetoreception. Hence, graphene created a more conducive environment for subsequent PEMF-stimulated neurogenic induction of hDPSCs through their mutual capacity to activate TRPC1with subsequent ROS production.

HEK293 cell response to static magnetic fields via the radical pair mechanism may explain therapeutic effects of pulsed electromagnetic fields.

PEMF (Pulsed Electromagnetic Field) stimulation has been used for therapeutic purposes for over 50 years including in the treatment of memory loss, depression, alleviation of pain, bone and wound healing, and treatment of certain cancers. However, the underlying cellular mechanisms mediating these effects have remained poorly understood. In particular, because magnetic field pulses will induce electric currents in the stimulated tissue, it is unclear whether the observed effects are due to the magnetic or electric component of the stimulation. Recently, it has been shown that PEMFs stimulate the formation of ROS (reactive oxygen species) in human cell cultures by a mechanism that requires cryptochrome, a putative magnetosensor. Here we show by qPCR analysis of ROS-regulated gene expression that simply removing cell cultures from the Earth’s geomagnetic field by placing them in a Low-Level Field condition induces similar effects on ROS signaling as does exposure of cells to PEMF. This effect can be explained by the so-called Radical Pair mechanism, which provides a quantum physical means by which the rates and product yields (e.g. ROS) of biochemical redox reactions may be modulated by magnetic fields. Since transient cancelling of the Earth’s magnetic field can in principle be achieved by PEMF exposure, we propose that the therapeutic effects of PEMFs may be explained by the ensuing modulation of ROS synthesis. Our results could lead to significant improvements in the design and therapeutic applications of PEMF devices.

Directionalities of magnetic fields and topographic scaffolds synergise to enhance MSC chondrogenesis

Mesenchymal stem cell (MSC) chondrogenesis is modulated by diverse biophysical cues. We have previously shown that brief, low-amplitude pulsed electromagnetic fields (PEMFs) differentially enhance MSC chondrogenesis in scaffold-free pellet cultures versus conventional tissue culture plastic (TCP), indicating an interplay between magnetism and micromechanical environment. Here, we examined the influence of PEMF directionality over the chondrogenic differentiation of MSCs laden on electrospun fibrous scaffolds of either random (RND) or aligned (ALN) orientations. Correlating MSCs’ chondrogenic outcome to pFAK activation and YAP localisation, MSCs on the RND scaffolds experienced the least amount of resting mechanical stress and underwent greatest chondrogenic differentiation in response to brief PEMF exposure (10 min at 1 mT) perpendicular to the dominant plane of the scaffolds (Z-directed). By contrast, in MSC-impregnated RND scaffolds, greatest mitochondrial respiration resulted from X-directed PEMF exposure (parallel to the scaffold plane), and was associated with curtailed chondrogenesis. MSCs on TCP or the ALN scaffolds exhibited greater resting mechanical stress and accordingly, were unresponsive, or negatively responsive, to PEMF exposure from all directions. The efficacy of PEMF-induced MSC chondrogenesis is hence regulated in a multifaceted manner involving focal adhesion dynamics, as well as mitochondrial responses, culminating in a final cellular response. The combined contributions of micromechanical environment and magnetic field orientation hence will need to be considered when designing magnetic exposure paradigms.

Pulsed Electromagnetic Fields Stimulate HIF-1α-Independent VEGF Release in 1321N1 Human Astrocytes Protecting Neuron-Like SH-SY5Y Cells from Oxygen-Glucose Deprivation.

Pulsed electromagnetic fields (PEMFs) are emerging as an innovative, non-invasive therapeutic option in different pathological conditions of the central nervous system, including cerebral ischemia. This study aimed to investigate the mechanism of action of PEMFs in an in vitro model of human astrocytes, which play a key role in the events that occur following ischemia. 1321N1 cells were exposed to PEMFs or hypoxic conditions and the release of relevant neurotrophic and angiogenic factors, such as VEGF, EPO, and TGF-β1, was evaluated by means of ELISA or AlphaLISA assays. The involvement of the transcription factor HIF-1α was studied by using the specific inhibitor chetomin and its expression was measured by flow cytometry. PEMF exposure induced a time-dependent, HIF-1α-independent release of VEGF from 1321N1 cells. Astrocyte conditioned medium derived from PEMF-exposed astrocytes significantly reduced the oxygen-glucose deprivation-induced cell proliferation and viability decrease in the neuron-like cells SH-SY5Y. These findings contribute to our understanding of PEMFs action in neuropathological conditions and further corroborate their therapeutic potential in cerebral ischemia.