title: Novel cell-free regeneration of bone using stem cell-derived growth factors.
abstract: OBJECTIVE
  Tissue engineering and regenerative medicine may now be used for the treatment of maxillofacial defects, but the related procedures have several limitations, including high capital investment, expensive cell culture techniques, and complicated safety and quality management issues. Stem cells secrete many cytokines that can affect cell mobilization and differentiation that accumulate in conditioned media. This study investigated the effects of stem cell-conditioned media from human bone marrow-derived mesenchymal stem cells (MSCs) on bone regeneration and its ability to induce endogeneous stem cell mobilization and bone regeneration.
  
  
  METHODS
  Human MSCs that were 70% to 80% confluent were refed with serum-free Dulbecco's modified Eagle medium, and the cell-cultured conditioned media were collected after 48 hours of incubation. The collected media were defined as cultured conditioned media from MSCs (MSC-CM). Rat bone-marrow-derived stem cells (rMSCs) were cultured with MSC-CM for 48 hours; then, cell mobilization and the expression of osteogenic-related genes were investigated. The presence of cytokines in MSC-CM was determined by enzyme-linked immunosorbent assay. Collagen sponge was then soaked in MSC-CM and grafted into rat calvarial bone defects. At 2 or 4 weeks after implantation of graft materials, implanted sections were evaluated by microcomputed tomography and histologic analysis.
  
  
  RESULTS
  MSC-CM enhanced the migration, proliferation, and expression of osteogenic marker genes, such as alkaline phosphatase, osteocalcin, and Runx2, of rMSCs in vitro. Cytokines such as insulinlike growth factor-1, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor were present in the MSC-CM. MSC-CM significantly increased the migration and expression of osteogenic-related genes of rMSCs. Early bone regeneration in rat calvaria was also observed.
  
  
  CONCLUSIONS
  These results suggest that MSC-CM may have potential for novel cell-free regeneration of bone.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. w-kat@med.nagoya-u.ac.jp
authors.forename: Wataru
authors.initials: W
authors.lastname: Katagiri
authors.forename: Masashi
authors.initials: M
authors.lastname: Osugi
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kawai
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012886:Skull / Q000378:metabolism; D023822:Tissue Engineering; D014945:Wound Healing / Q000187:drug effects
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins