title: The effect of BMP-7 gene activated muscle tissue implants on the repair of large segmental bone defects.
abstract: BACKGROUND
  This study was conducted in order to investigate the effect of Bone Morphogenetic Protein-7 (BMP-7) transduced muscle cells on bone formation and to further develop an innovative abbreviated ex vivo gene therapy for bone repair. As conventional ex vivo gene therapy methods require an elaborative and time-consuming extraction and expansion of cells we evaluated an expedited approach. Fragments of muscle tissue were directly activated by BMP-7 cDNA and implanted into bone defects.
  
  
  METHODS
  25 male, syngeneic Fischer 344 rats were used in the present study. Muscle tissue was harvested from two donor rats and either transduced with an adenovirus carrying the BMP-7 cDNA or remained unmodified. 5mm osseous defects in the right femora of 23 rats were treated with either unmodified muscle tissue (control group) or BMP-7 activated muscle tissue (treatment group). Six weeks after surgery, rat femora were evaluated by radiographs, micro-computed tomography (μCT) and histology.
  
  
  RESULTS
  Implantation of BMP-7 activated muscle grafts led to bony bridging in 5 out of 12 defects (41.7%) and to bone formation without bridging in 2 out of 12 defects. In 2 femoral defects of this group radiographs, μCT-imaging and histology did not reveal significant mineralization. Three animals of the BMP-7 treatment group had to be euthanized due to serious wound infection. The bone volume of the treatment group was significantly (p=0.007) higher compared to the control group.
  
  
  CONCLUSIONS
  This study shows that BMP-7 gene activated muscle fragments have the potential to regenerate critical-size segmental bone defects in rats. However, further development of this promising expedited treatment modality is required to improve the healing rate and to investigate if the high infection rate is related to treatment with BMP-7 activated muscle grafts.
authors.affiliation: Department of Trauma and Reconstructive Surgery and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany. Electronic address: volker.betz@yahoo.com.
authors.forename: Volker M
authors.initials: VM
authors.lastname: Betz
authors.affiliation: Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Oliver B
authors.initials: OB
authors.lastname: Betz
authors.affiliation: Department of Trauma and Reconstructive Surgery and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Rosin
authors.affiliation: Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Keller
authors.affiliation: Sirion Biotech GmbH, Martinsried, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thirion
authors.affiliation: Sirion Biotech GmbH, Martinsried, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Salomon
authors.affiliation: Department of Trauma and Reconstructive Surgery and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Manthey
authors.affiliation: Institute of Biomechanics, Trauma Center Murnau, Murnau, Germany; Paracelsus Medical University, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Augat
authors.affiliation: Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Jansson
authors.affiliation: Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Müller
authors.affiliation: Department of Trauma and Reconstructive Surgery and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rammelt
authors.affiliation: Department of Trauma and Reconstructive Surgery and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Zwipp
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D001861:Bone Regeneration; D001842:Bone and Bones / Q000473:pathology*; D004195:Disease Models, Animal; D015316:Genetic Therapy; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology* / Q000637:transplantation; D010012:Osteogenesis; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta
chemical_list: D055419:Bone Morphogenetic Protein 7; D016212:Transforming Growth Factor beta
keywords: BMP-7; Bone defect; Bone repair; Gene therapy; Muscle tissue; Tissue engineering