title: An injectable method for noninvasive spine fusion.
abstract: BACKGROUND
  Bone morphogenetic proteins (BMPs) induce bone formation but are difficult to localize, and subsequent diffusion from the site of interest and short half-life reduce the efficacy of the protein. Currently, spine fusion requires stripping, decortications of the transverse processes, and an autograft harvest procedure. Even in combination with BMPs, clinical spinal fusion has a high failure rate, presumably because of difficulties in localizing sufficient levels of BMP.
  
  
  OBJECTIVE
  The goal was to achieve reliable spine fusion through a single injection of a cell-based gene therapy system without the need for any surgical intervention.
  
  
  METHODS
  Eighty-seven immunodeficient (n=44) and immune-competent (n=43) mice were injected along the paraspinous musculature to achieve rapid induction of heterotopic ossification (HO) and ultimately spinal arthrodesis.
  
  
  METHODS
  Immunodeficient and immune-competent mice were injected with fibroblasts, transduced with an adenoviral vector to express BMP2, along the paraspinous musculature. Bone formation was evaluated via radiographs, microcomputed tomography, and biomechanical analysis.
  
  
  RESULTS
  ew bridging bone between the vertebrae and the fusion to adjacent skeletal bone was obtained as early as 2 weeks. Reduction in spine flexion-extension also occurred as early as 2 weeks after injection of the gene therapy system, with greater than 90% fusion by 4 weeks in all animals regardless of their genetic background.
  
  
  CONCLUSIONS
  Injection of our cell-based system into the paraspinous musculature induces spinal fusion that is dependent neither on the cell type nor on the immune status. These studies are the first to harness HO in an immune-competent model as a noninvasive injectable system for clinically relevant spinal fusion and may one day impact human spinal arthrodesis.
authors.affiliation: Department of Bioengineering, Rice University, MS 142, 6100 Main St, Houston, TX 77005, USA.
authors.forename: Ronke M
authors.initials: RM
authors.lastname: Olabisi
authors.forename: ZaWaunyka
authors.initials: Z
authors.lastname: Lazard
authors.forename: Michael H
authors.initials: MH
authors.lastname: Heggeness
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Moran
authors.forename: John A
authors.initials: JA
authors.lastname: Hipp
authors.forename: Ashvin K
authors.initials: AK
authors.lastname: Dewan
authors.forename: Alan R
authors.initials: AR
authors.lastname: Davis
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Olmsted-Davis
mesh_terms: D000256:Adenoviridae; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000235:genetics; D013123:Spinal Fusion / Q000379:methods*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2