title: A defined mix of cytokines mimics conditioned medium from cultures of bone marrow-derived mesenchymal stem cells and elicits bone regeneration.
abstract: OBJECTIVE
  We previously reported that conditioned medium from cultures of bone marrow-derived mesenchymal stem cells have strong potential to accelerate bone regeneration. We now examine in vitro and in vivo a defined cytokine cocktail that mimics the effects of conditioned medium on bone regeneration.
  
  
  METHODS
  A cocktail of recombinant human insulin-like growth factor-1, vascular endothelial growth factor-A and transforming growth factor-β1 was prepared at concentrations similar to those in conditioned medium. Conversely, these cytokines were depleted from conditioned medium, and the effects of the cocktail, the conditioned medium and the cytokine-depleted conditioned medium on bone regeneration were evaluated in vitro and in vivo.
  
  
  RESULTS
  The cytokine cocktail and conditioned medium enhanced cell migration, tube formation, and expression of osteogenic and angiogenic genes. Depletion of cytokines significantly decreased the effects of conditioned medium in vitro. Similarly, the cytokine cocktail and conditioned medium, but not cytokine-depleted medium, increased bone regeneration in damaged rat calvarial bone. Immunohistochemistry indicated that the cytokine cocktail and conditioned medium strongly enhanced recruitment of endogenous stem cells and endothelial cells.
  
  
  CONCLUSIONS
  The data indicate that the cytokine cocktail and conditioned medium enhance the migration of stem cells and endothelial cells to damaged bone, and elicit osteogenesis and angiogenesis.
authors.affiliation: Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Katagiri
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sakaguchi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Wakayama
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Osugi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hibi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D001861:Bone Regeneration / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines