title: Sox9 gene transfer enhanced regenerative effect of bone marrow mesenchymal stem cells on the degenerated intervertebral disc in a rabbit model.
abstract: OBJECTIVE
  The effect of Sox9 on the differentiation of bone marrow mesenchymal stem cells (BMSCs) to nucleus pulposus (NP)-like (chondrocyte-like) cells in vitro has been demonstrated. The objective of this study is to investigate the efficacy and feasibility of Sox9-transduced BMSCs to repair the degenerated intervertebral disc in a rabbit model.
  
  
  METHODS
  Fifty skeletally mature New Zealand white rabbits were used. In the treatment groups, NP tissue was aspirated from the L2-L3, L3-L4, and L4-L5 discs in accordance with a previously validated rabbit model of intervertebral disc degeneration and then treated with thermogelling chitosan (C/Gp), GFP-transduced autologous BMSCs with C/Gp or Sox9-transduced autologous BMSCs with C/Gp. The role of Sox9 in the chondrogenic differentiation of BMSCs embedded in C/Gp gels in vitro and the repair effect of Sox9-transduced BMSCs on degenerated discs were evaluated by real-time PCR, conventional and quantitative MRI, macroscopic appearance, histology and immunohistochemistry.
  
  
  RESULTS
  Sox9 could induce the chondrogenic differentiation of BMSCs in C/Gp gels and BMSCs could survive in vivo for at least 12 weeks. A higher T2-weighted signal intensity and T2 value, better preserved NP structure and greater amount of extracellular matrix were observed in discs treated with Sox9-transduced BMSCs compared with those without transduction.
  
  
  CONCLUSIONS
  Sox9 gene transfer could significantly enhance the repair effect of BMSCs on the degenerated discs.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China; Department of Orthopaedic Surgery, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, the Central Hospital of Xuzhou, Affiliated Hospital of Medical College of Southeast University, Xuzhou, PR China.
authors.forename: Guangwang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Youzhuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001861:Bone Regeneration / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D011817:Rabbits; D055758:SOX9 Transcription Factor / Q000235:genetics*
chemical_list: D055758:SOX9 Transcription Factor