title: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Treatment of synovial cells with LR-PRP and RBCs resulted in significant cell death and proinflammatory mediator production.
  
  
  CONCLUSIONS
  Clinicians should consider using leukocyte-poor, RBC-free formulations of PRP when administering intra-articularly.
authors.affiliation: Jason L. Dragoo, Department of Orthopaedic Surgery, Stanford University, 450 Broadway Street, Pavilion C, 4th Floor, Redwood City, CA 94063-6342, USA. jdragoo@stanford.edu.
authors.forename: Hillary J
authors.initials: HJ
authors.lastname: Braun
authors.forename: Hyeon Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Constance R
authors.initials: CR
authors.lastname: Chu
authors.forename: Jason L
authors.initials: JL
authors.lastname: Dragoo
mesh_terms: D002021:Buffers; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D004912:Erythrocytes / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D010710:Phosphates; D053657:Platelet-Rich Plasma / Q000166:cytology*; D012965:Sodium Chloride; D013583:Synovial Membrane / Q000166:cytology*
chemical_list: D002021:Buffers; D016207:Cytokines; D010710:Phosphates; D012965:Sodium Chloride
keywords: inflammation; osteoarthritis; platelet-rich plasma; synoviocytes