Targeting Mesenchymal Stromal Cells/Pericytes (MSCs) With Pulsed Electromagnetic Field (PEMF) Has the Potential to Treat Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium (synovitis), with inflammatory/immune cells and resident fibroblast-like synoviocytes (FLS) acting as major players in the pathogenesis of this disease. The resulting inflammatory response poses considerable risks as loss of bone and cartilage progresses, destroying the joint surface, causing joint damage, joint failure, articular dysfunction, and pre-mature death if left untreated. At the cellular level, early changes in RA synovium include inflammatory cell infiltration, synovial hyperplasia, and stimulation of angiogenesis to the site of injury. Different angiogenic factors promote this disease, making the role of anti-angiogenic therapy a focus of RA treatment. To control angiogenesis, mesenchymal stromal cells/pericytes (MSCs) in synovial tissue play a vital role in tissue repair. While recent evidence reports that MSCs found in joint tissues can differentiate to repair damaged tissue, this repair function can be repressed by the inflammatory milieu. Extremely-low frequency pulsed electromagnetic field (PEMF), a biophysical form of stimulation, has an anti-inflammatory effect by causing differentiation of MSCs. PEMF has also been reported to increase the functional activity of MSCs to improve differentiation to chondrocytes and osteocytes. Moreover, PEMF has been demonstrated to accelerate cell differentiation, increase deposition of collagen, and potentially return vascular dysfunction back to homeostasis. The aim of this report is to review the effects of PEMF on MSC modulation of cytokines, growth factors, and angiogenesis, and describe its effect on MSC regeneration of synovial tissue to further understand its potential role in the treatment of RA.
Objective: Pulsed electromagnetic field (PEMF) therapy is a potentially useful treatment for osteoarthritis (OA), but its effectiveness is still controversial. This study aimed to examine the effects of PEMF therapy and PEMF parameters on symptoms and quality of life (QOL) in patients with OA.
Methods: Cochrane Central Register of Controlled Trials, PubMed, CINAHL, EMBASE, PEDro, clinical trial registers, and reference lists were searched until April 2019. This study examined randomized, placebo-controlled trials, patients with OA, symptom and/or QOL related outcomes, and articles published in English. Two authors extracted data and completed quality assessment.
Results: Sixteen studies were included in our systematic review, while 15 studies with complete data were included in the meta-analysis. Our primary outcome was the standardized mean difference, which was equal to the treatment effect in the PEMF group minus the treatment effect in the placebo group divided by the pooled standard deviation. For pain, the standardized mean difference was 1.06 (95% CI = 0.61 to 1.51), for stiffness 0.37 (95% CI = 0.07 to 0.67), for function 0.46 (95% CI = 0.14 to 0.78), and for QOL 1.49 (95% CI = -0.06 to 3.04). PEMF parameters did not influence symptoms.
Conclusions: Compared with placebo, there was a beneficial effect of PEMF therapy on pain, stiffness, and physical function in patients with OA. Duration of treatment may not be a critical factor in pain management. Further studies are required to confirm the effects of PEMF therapy on QOL.
Impact: Our study suggests that PEMF therapy has clinically significant effects on pain in patients with OA. The current evidence was limited to the short-term effects of PEMF therapy.