title: Ex vivo expanded haematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms.
abstract: BACKGROUND
  Although dermal wounds are common, treatment remains limited and largely ineffective. Recent studies suggest that therapeutic application of progenitor cells is useful for tissue regeneration.
  
  
  OBJECTIVE
  We here investigated the effects exerted by the recently characterized immortalized haematopoietic progenitor cell line DKmix and their conditioned medium in a murine wound healing model.
  
  
  RESULTS
  Injection of both DKmix cells and their conditioned medium accelerated wound repair between days 3 and 10 compared with PBS-injected control mice (n = 8, P < 0.01 DKmix cells vs control, P < 0.01 conditioned medium vs control at day 6). The treated groups exhibited more CD31(+)-capillaries at day 6 after injury compared with the control group (n = 4, P < 0.01 DKmix cells vs control, P < 0.001 conditioned medium vs control), whereas there was no change in infiltrated CD68(+) macrophages. Conditioned medium of DKmix cells induced tube formation of human endothelial cells in Matrigel assays (n = 4-6, P < 0.05 conditioned medium vs control) as well as migration (n = 4, P < 0.01 conditioned medium vs control) and proliferation of murine 3T3 fibroblasts (n = 5, P < 0.05 conditioned medium vs control). Abundant levels of matrix metalloproteinase -2 and -9 in the supernatants were detected. Protein arrays of the supernatants revealed a strong secretion of cytokines and growth factors, such as monocyte chemoatractant protein-1 and GM-CSF from DKmix cells.
  
  
  CONCLUSIONS
  DKmix cells improve skin-substitute wound healing by promoting angiogenesis as well as migration and proliferation of fibroblasts. These data suggest that immortalized haematopoietic progenitor cells significantly improve dermal wound healing by paracrine effects.
authors.affiliation: Cardiovascular Center, Cardiology, University Hospital Zürich, Zürich, Switzerland. Christian.Templin@usz.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Templin
authors.forename: Karsten
authors.initials: K
authors.lastname: Grote
authors.forename: Kai
authors.initials: K
authors.lastname: Schledzewski
authors.forename: Jelena-Rima
authors.initials: JR
authors.lastname: Ghadri
authors.forename: Sabine
authors.initials: S
authors.lastname: Schnabel
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Napp
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Kurzen
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenen
authors.forename: Jörg
authors.initials: J
authors.lastname: Faulhaber