title: The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries.
abstract: BACKGROUND
  Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair.
  
  
  METHODS
  TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III.
  
  
  CONCLUSIONS
  These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects.
authors.affiliation: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA. drzhouyq@gmail.com.|Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu, Shanghai, 200003, China. drzhouyq@gmail.com.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA. jianying@pitt.edu.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu, Shanghai, 200003, China. drisland@vip.sina.com.
authors.forename: Haishan
authors.initials: H
authors.lastname: Wu
authors.affiliation: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA. hoganmv@upmc.edu.
authors.forename: MaCalus V
authors.initials: MV
authors.lastname: Hogan
authors.affiliation: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, BST, E1640, Pittsburgh, PA, 15213, USA. wanghc@pitt.edu.
authors.forename: James H-C
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D053657:Platelet-Rich Plasma; D011817:Rabbits; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013710:Tendons / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D024043:Collagen Type II; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone