title: The systemic influence of platelet-derived growth factors on bone marrow mesenchymal stem cells in fracture patients.
abstract: BACKGROUND
  Fracture healing is a complex process regulated by a variety of cells and signalling molecules which act both locally and systemically. The aim of this study was to investigate potential changes in patients' mesenchymal stem cells (MSCs) in the iliac crest (IC) bone marrow (BM) and in peripheral blood (PB) in relation to the severity of trauma and to correlate them with systemic changes reflective of inflammatory and platelet responses following fracture.
  
  
  METHODS
  ICBM samples were aspirated from two trauma groups: isolated trauma and polytrauma (n = 8 and 18, respectively) at two time-points post-fracture and from non-trauma controls (n = 7). Matched PB was collected every other day for a minimum of 14 days. BM MSCs were enumerated using colony forming-fibroblast (CFU-F) assay and flow cytometry for the CD45-CD271+ phenotype.
  
  
  RESULTS
  Regardless of the severity of trauma, no significant increase or decrease in BM MSCs was observed following fracture and MSCs were not mobilised into PB. However, direct positive correlations were observed between changes in the numbers of aspirated BM MSCs and time-matched changes in their serum PDGF-AA and -BB. In vitro, patients' serum induced MSC proliferation in a manner reflecting changes in PDGFs. PDGF receptors CD140a and CD140b were expressed on native CD45-CD271+ BM MSCs (average 12% and 64%, respectively) and changed over time in direct relationship with platelets/PDGFs.
  
  
  CONCLUSIONS
  Platelet lysates and other platelet-derived products are used to expand MSCs ex vivo. This study demonstrates that endogenous PDGFs can influence MSC responses in vivo. This indicates a highly dynamic, rather than static, MSC nature in humans.
authors.forename: Hiang Boon
authors.initials: HB
authors.lastname: Tan
authors.affiliation: NIHR Leeds Biomedical Research Unit, Chapel Allerton Hospital, Leeds West Yorkshire, Leeds LS7 4SA, UK. pgiannoudi@aol.com.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Giannoudis
authors.forename: Sally A
authors.initials: SA
authors.lastname: Boxall
authors.forename: Dennis
authors.initials: D
authors.lastname: McGonagle
authors.forename: Elena
authors.initials: E
authors.lastname: Jones
mesh_terms: D000328:Adult; D001773:Blood Cells; D001854:Bone Marrow Cells; D002452:Cell Count; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005260:Female; D005347:Fibroblasts; D005434:Flow Cytometry; D050723:Fractures, Bone / Q000503:physiopathology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D009104:Multiple Trauma / Q000503:physiopathology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D055815:Young Adult
chemical_list: D010982:Platelet-Derived Growth Factor