Allogenic Pure Platelet-Rich Plasma Therapy for Adhesive Capsulitis: A Bed-to-Bench Study With Propensity Score Matching Using a Corticosteroid Control Group

Abstract

Background: While platelet-rich plasma (PRP) has been widely studied for musculoskeletal disorders, few studies to date have reported its use for adhesive capsulitis (AC). Fully characterized and standardized allogenic PRP may provide clues to solve the underlying mechanism of PRP with respect to synovial inflammation and thus may clarify its clinical indications. Purpose: To clinically evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with AC and to assess the effects of pure PRP on synoviocytes with or without inflammation in vitro. Study Design: Controlled laboratory study and cohort study; Level of evidence, 3. Methods: For the clinical analysis, a total of 15 patients with AC received an ultrasonography-guided intra-articular PRP injection and were observed for 6 months. Pain, range of motion (ROM), muscle strength, shoulder function, and overall satisfaction in the patients were evaluated using questionnaires at 1 week as well as at 1, 3, and 6 months after the PRP injection and results were compared with the results of a propensity score−matched control group that received a corticosteroid injection (40 mg triamcinolone acetonide). For the in vitro analysis, synoviocytes were cultured with or without interleukin-1β (IL-1β) and PRP. The gene expression of proinflammatory and anti-inflammatory cytokines as well as matrix enzymes and their inhibitors was evaluated. Results: At 6-month follow-up, pure PRP significantly decreased pain and improved ROM, muscle strength, and shoulder function to levels comparable with those after a corticosteroid injection. All pain values, strength measurements, and functional scores significantly improved up to 6 months in the PRP group, but these measures improved up to 3 months and then were decreased at 6 months in the corticosteroid group. ROM was significantly improved in the 2 groups at 6 months compared with baseline. Allogenic PRP did not cause adverse events. For the in vitro findings, PRP induced inflammation but significantly improved the IL 1β−induced synovial inflammatory condition by decreasing proinflammatory cytokines such as IL-1β, tumor necrosis factor−α, IL-6, cyclooxygenase-2, and microsomal prostaglandin E synthase−1 and decreased matrix enzymes (matrix metalloproteinase−1, −3, and −13 as well as a disintegrin and metalloproteinase with thrombospondin motifs−4 and −5) and further increasing anti-inflammatory cytokines such as vasoactive intestinal peptide. Conclusion: This study showed that PRP decreased pain and improved shoulder ROM and function to an extent comparable with that of a corticosteroid in patients with AC. Allogenic pure PRP acted in a pleiotropic manner and decreased proinflammatory cytokines only in the inflammatory condition. Clinical Relevance: Allogenic PRP could be a treatment option for the inflammatory stage of AC.