The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes: Implications for Intra-articular Injury and Therapy

Abstract

Background: The effect of platelet-rich plasma (PRP) on chondrocytes has been studied in cell and tissue culture, but considerably less attention has been given to the effect of PRP on synoviocytes. Fibroblast-like synoviocytes (FLS) compose 80% of the normal human synovium and produce cytokines and matrix metalloproteinases that can mediate cartilage catabolism. Purpose: To compare the effects of leukocyte-rich PRP (LR-PRP), leukocyte-poor PRP (LP-PRP), red blood cell (RBC) concentrate, and platelet-poor plasma (PPP) on human FLS to determine whether leukocyte and erythrocyte concentrations of PRP formulations differentially affect the production of inflammatory mediators. Study Design: Controlled laboratory study. Methods: Peripheral blood was obtained from 4 donors and processed to create LR-PRP, LP-PRP, RBCs, and PPP. Human synoviocytes were cultured for 96 hours with the respective experimental conditions using standard laboratory conditions. Cell viability and inflammatory mediator production were then evaluated. Results: Treatment with LR-PRP resulted in significantly greater synoviocyte death (4.9% ± 3.1%) compared with LP-PRP (0.72% ± 0.70%; P = .035), phosphate-buffered saline (PBS) (0.39% ± 0.27%; P = .018), and PPP (0.26% ± 0.30%; P = .013). Synoviocytes treated with RBC concentrate demonstrated significantly greater cell death (12.5% ± 6.9%) compared with PBS ( P < .001), PPP ( P < .001), LP-PRP ( P < .001), and LR-PRP (4.9% ± 3.1%; P < .001). Interleukin (IL)–1β content was significantly higher in cultures treated with LR-PRP (1.53 ± 0.86 pg/mL) compared with those treated with PBS (0.22 ± 0.295 pg/mL; P < .001), PPP (0.11 ± 0.179 pg/mL; P < .001), and RBCs (0.64 ± 0.58 pg/mL; P = .001). IL-6 content was also higher with LR-PRP (32,097.82 ± 22,844.300 pg/mL) treatment in all other groups ( P < .001). Tumor necrosis factor–α levels were greatest in LP-PRP (9.97 ± 3.110 pg/mL), and this was significantly greater compared with all other culture conditions ( P < .001). Interferon-γ levels were greatest in RBCs (64.34 ± 22.987 pg/mL) and significantly greater than all other culture conditions ( P < .001). Conclusion: Treatment of synovial cells with LR-PRP and RBCs resulted in significant cell death and proinflammatory mediator production. Clinical Relevance: Clinicians should consider using leukocyte-poor, RBC-free formulations of PRP when administering intra-articularly.