title: Leukocyte-Reduced Platelet-Rich Plasma Normalizes Matrix Metabolism in Torn Human Rotator Cuff Tendons.
abstract: BACKGROUND
  The optimal platelet-rich plasma (PRP) for treatment of supraspinatus tendinopathy has not been determined.
  
  
  OBJECTIVE
  To evaluate the effect of low- versus high-leukocyte concentrated PRP products on catabolic and anabolic mediators of matrix metabolism in diseased rotator cuff tendons.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Diseased supraspinatus tendons were treated with PRP made by use of 2 commercial systems: Arthrex Autologous Conditioned Plasma Double Syringe System (L(lo) PRP) and Biomet GPS III Mini Platelet Concentrate System (L(hi) PRP). Tendon explants were placed in 6-well plates and cultured in L(lo) PRP, L(hi) PRP, or control media (Dulbecco's Modified Eagle Medium + 10% fetal bovine serum) for 96 hours. Tendons were processed for hematoxylin-eosin histologic results and were scored with the modified Bonar scale. Group 1 tendons were defined as moderate tendinopathy (Bonar score <3); group 2 tendons were assessed as severely affected (Bonar score = 3). Transforming growth factor β-1 (TGFβ-1), interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8), and matrix metalloproteinase-9 (MMP-9) concentrations in PRP media were measured by use of enzyme-linked immunosorbent assay after 96 hours of culture with diseased tendon. Tendon messenger RNA expression of collagen type I (COL1A1), collagen type III (COL3A1), cartilage oligomeric matrix protein (COMP), MMP-9, MMP-13, and IL-1β was measured with real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  Leukocytes and platelets were significantly more concentrated in L(hi) PRP compared with L(lo) PRP. Increased IL-1β was present in L(hi) PRP after culture with group 1 tendons. IL-6 was increased in L(hi) PRP after culture with group 2 tendons. Both TGFβ-1 and MMP-9 were increased in L(hi) PRP after culture with either tendon group. In L(lo) PRP cultures, IL-1Ra:IL-1β in PRP used as media and COL1A1:COL3A1 gene expression were increased for group 1 tendon cultures. Gene expression of MMP-9 and IL-1β was increased in group 2 tendons cultured in L(lo) PRP. There was no significant difference in the expression of MMP-13 or COMP in either group of tendons cultured in L(lo) PRP or L(hi) PRP.
  
  
  CONCLUSIONS
  L(lo) PRP promotes normal collagen matrix synthesis and decreases cytokines associated with matrix degradation and inflammation to a greater extent than does L(hi) PRP in moderately degenerative tendons. In severely degenerative tendons, neither PRP preparation enhanced matrix synthesis.
  
  
  CONCLUSIONS
  L(lo) PRP may promote healing in moderately degenerative rotator cuff tendons.
authors.affiliation: Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cross
authors.affiliation: Department of Orthopedics, Rush University Medical Center, Chicago, Illinois, USA cole.research@rushortho.com.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cole
authors.affiliation: Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Kaylan P
authors.initials: KP
authors.lastname: Spatny
authors.affiliation: Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Sundman
authors.affiliation: Department of Orthopedics, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Romeo
authors.affiliation: Department of Orthopedics, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Greg P
authors.initials: GP
authors.lastname: Nicholson
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Department of Clinical Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Fortier
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D052256:Tendinopathy / Q000378:metabolism* / Q000628:therapy; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D016326:Extracellular Matrix Proteins; D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha
keywords: biological healing enhancement; growth factors; platelet-rich plasma; rotator cuff; shoulder