title: Two-stage therapeutic utility of ectopically formed bone tissue in skeletal muscle induced by adeno-associated virus containing bone morphogenetic protein-4 gene.
abstract: BACKGROUND
  The major disadvantage of using a stem cell-based bone morphogenetic protein-4 (BMP4) gene therapy for skull defect is the overgrowth of generated bone tissue in situ. In the present study, to overcome bony overgrowth of stem cell based-gene therapy, a new strategy of two-stage bone tissue engineering by an adeno-associated virus containing BMP4 gene (AAV-BMP4) gene therapy was used.
  
  
  METHODS
  AAV-BMP4 was purposely implanted in the skeletal muscle of mice to generate ectopic bone tissues during the first stage. Next, the newly formed ectopic bone tissues were harvested and then transplanted to repair the mouse skull defect during the second stage.
  
  
  RESULTS
  The results showed that skeletal muscle implantation of AAV-BMP4 yielded a large amount of new bone tissues. The ectopic bone tissues can be harvested as a bone graft and can successfully repair the mouse skull defect without any bony overgrowth in situ.
  
  
  CONCLUSIONS
  The results indicate that the bone tissues purposely generated by AAV-BMP4 in the skeletal muscle may be a new alternative of bone grafting for clinical purposes.
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tian
authors.affiliation: Department of Geriatrics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, 471009, Henan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qi
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
authors.forename: Guanlei
authors.initials: G
authors.lastname: Liu
authors.affiliation: Molecular Therapy Laboratory, Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Stem Cell Research Center, University of Pittsburgh School of Medicine, 206 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China. liguangheng@hotmail.com.
authors.forename: Guangheng
authors.initials: G
authors.lastname: Li
mesh_terms: D000256:Adenoviridae; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000502:physiology*; D016025:Bone Transplantation; D001842:Bone and Bones; D002828:Choristoma; D048091:Guided Tissue Regeneration; D006801:Humans; D016513:Mice, SCID; D018482:Muscle, Skeletal; D014161:Transduction, Genetic
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4