title: Synergistic effect of bone morphogenetic proteins 2 and 7 by ex vivo gene therapy in a rat spinal fusion model.
abstract: BACKGROUND
  Previous studies have suggested that the co-expression of two different bone morphogenetic protein (BMP) genes can result in the production of heterodimeric BMPs that may be more potent than homodimers. In this study, combined BMP-2 and BMP-7 gene transfer was performed ex vivo to compare the resulting new bone formation with that of single-BMP gene transfer in a rat spinal fusion model.
  
  
  METHODS
  Forty-four athymic rats underwent posterolateral fusion at L4-L5 and were implanted with a collagen sponge containing human adipose-derived stem cells. Group A received untreated cells, and the remaining groups received cells transfected with various genes in a lentivirus vector. The transferred genes were GFP (green fluorescent protein) in Group B, BMP-2 in Group C, BMP-7 in Group D, and both BMP-2 and BMP-7 in Group E. In vitro production of BMP-2 and BMP-7 was quantified by means of an enzyme-linked immunosorbent assay (ELISA) specific to BMP-2 or BMP-7. Osseous fusion was quantified with use of radiography and microcomputed tomography.
  
  
  RESULTS
  ELISA demonstrated that Group E, which was treated with both BMP-2 and BMP-7, produced less than one-fourth as much BMP as the groups treated with a single transfected BMP (Groups C and D). Radiographs showed that all of the spines in Groups C, D, and E appeared to be fused by eight weeks; the spines in Groups A and B showed minimal evidence of new bone formation. Measurements confirmed that the mean bone formation area was significantly greater in Groups C, D, and E compared with Groups A and B (p &lt; 0.001). In addition, the bone formation area was significantly greater in Group E compared with Groups C and D (p &lt; 0.001).
  
  
  CONCLUSIONS
  Combined BMP-2 and BMP-7 ex vivo gene transfer was found to be significantly more effective for inducing new bone formation compared with ex vivo gene transfer of an individual BMP in a rat spinal fusion model.
  
  
  CONCLUSIONS
  Combined BMP-2 and BMP-7 therapy may lead to efficient bone regeneration.
authors.affiliation: Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. takashikaito@gmail.com
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaito
authors.forename: Jared
authors.initials: J
authors.lastname: Johnson
authors.forename: Jessica
authors.initials: J
authors.lastname: Ellerman
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.forename: Mehmet
authors.initials: M
authors.lastname: Aydogan
authors.forename: Mongkol
authors.initials: M
authors.lastname: Chatsrinopkun
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ngo
authors.forename: Christine
authors.initials: C
authors.lastname: Choi
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000627:therapeutic use*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects / Q000235:genetics*; D018014:Gene Transfer Techniques; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000601:surgery; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D011859:Radiography; D051381:Rats; D011923:Rats, Nude; D013123:Spinal Fusion / Q000379:methods*; D016896:Treatment Outcome
chemical_list: C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7