title: Tendon derived stem cells promote platelet-rich plasma healing in collagenase-induced rat achilles tendinopathy.
abstract: OBJECTIVE
  Tendon injuries are common, difficult to cure and usually healed with fibrosis and scar tissue. The aim of this study was to evaluate tendon derived stem cells (TDSCs) and platelet rich plasma (PRP) in the treatment of collagenase induced Achilles tendinopathy in rat.
  
  
  METHODS
  Four and 8 weeks (n=18) after TDSCs, PRP, PRP with TDSC or PBS (control) injection into collagenase or saline (sham) injected rat Achilles tendon, tendon tissue was harvested and tendon quality was evaluated by histology and biomechanical testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling pathway and tenocyte-related genes were detected by western blot analysis.
  
  
  RESULTS
  Compared to the control, PRP treatment resulted in better healing of injured tendons with improved histological outcomes and biomechanical functions. The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP treatment alone. TDSC injection alone had little effect on tendon healing. PRP and PRP with TDSC treatments of collagenase induced tendon injuries also increased the mRNA and protein expression of tenocyte-related genes (type I collagen, SCX, Tenascin C) and activated the focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) 1/2 signaling pathways. Treatment of TDSCs in vitro with 10% PRP significantly increased the phosphorylation levels of FAK and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and Tenascin C). Inhibition of the FAK and ERK1/2 signaling pathways abolished the effect of PRP.
  
  
  CONCLUSIONS
  This study concludes that PRP combined with TDSCs is potentially effective for the treatment of tendinopathy. The PRP induced, FAK and ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests that the beneficial healing effect of the PRP with TDSC combination might occur by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a PRP with TDSC combination therapy may be clinically useful.
authors.affiliation: Department of Orthopaedics, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Jun-Peng
authors.initials: JP
authors.lastname: Liu
authors.forename: Kang-Lai
authors.initials: KL
authors.lastname: Tang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Wang
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Cai
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Liu
mesh_terms: D000125:Achilles Tendon / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D024042:Collagen Type I / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D006801:Humans; D053657:Platelet-Rich Plasma; D051381:Rats; D033581:Stem Cell Transplantation; D052256:Tendinopathy / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D017364:Collagenases