title: The role of cell type in bone healing mediated by ex vivo gene therapy.
abstract: BACKGROUND
  The ideal cellular vehicle for use in cell-mediated gene therapy to enhance bone healing has not yet been identified. The purpose of this study was to compare the capacity of two types of cells transduced with retro-bone morphogenetic protein 4 (BMP4)-muscle-derived cells (MDCs) and unfractioned bone marrow stromal cells (BMSCs).
  
  
  METHODS
  Primary rat MDCs and unfractioned rat BMSCs were transduced with a retrovirus to express BMP4. A 7-mm, critical-sized femur defect was created in adult rats, and 5 x 10(6) transduced cells were implanted into the femoral defect. Bone healing was monitored radiographically and histologically at 4, 8, and 12 weeks post-implantation.
  
  
  RESULTS
  All specimens in the MDC-BMP4 group and BMSC-BMP4 group showed a bridging callus at 8 and 12 weeks. At 12 weeks post-implantation the calluses of the MDC-BMP4 femora displayed significantly higher bone photodensity than the BMSC-BMP4 femora (P<0.05). Histomorphometry revealed no difference between the two treatment groups. However, non-union between newly formed and original bone was observed in none of the MDC femora but in six femora from the BMSC-BMP4 group.
  
  
  CONCLUSIONS
  Both MDCs and unfractioned BMSCs can improve healing of a critical-sized bone defect following transduction of the cells with retroBMP4. However, MDCs appear to yield superior results when compared with BMSCs in terms of improved healing of segmental defects.
authors.affiliation: Department of Trauma and Reconstructive Surgery, University of Leipzig, Liebigstrasse 20a, 04103 Leipzig, Germany. rost@medizin.uni-leipzig.de
authors.forename: Tim
authors.initials: T
authors.lastname: Rose
authors.forename: Hairong
authors.initials: H
authors.lastname: Peng
authors.forename: Hsain-Chung
authors.initials: HC
authors.lastname: Shen
authors.forename: Arvydas
authors.initials: A
authors.lastname: Usas
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Helmut
authors.initials: H
authors.lastname: Lill
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Fu
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019902:Chondrocytes / Q000473:pathology; D015316:Genetic Therapy; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017154:Stromal Cells / Q000502:physiology; D014161:Transduction, Genetic; D014945:Wound Healing / Q000502:physiology*
chemical_list: C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins