title: Emerging ideas: treatment of precollapse osteonecrosis using stem cells and growth factors.
abstract: BACKGROUND
  Osteonecrosis (ON) of the femoral head is a devastating disease affecting young patients at their most productive age, causing major socioeconomic burdens. ON is associated with various etiologic factors, and the pathogenesis of the disease is unknown. Most investigators believe the disease is the result of secondary microvascular compromise with subsequent bone and marrow cell death and defective bone repair.
  
  
  OBJECTIVE
  We hypothesize that local delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-6 (BMP-6), which induces angiogenesis and osteogenesis respectively, will reverse the disease process and provide a treatment for precollapse ON.
  
  
  METHODS
  We will use genetically engineered bone marrow stem cells, carrying VEGF and BMP-6 genes, to enhance angiogenesis and osteogenesis in necrotic bone of an animal model, by local delivery of growth factor in addition to the bone-forming property of the stem cells. The participation, localization, and fate of the stem cells in the repair process will be evaluated by tracing marker-gene product. Osteogenesis and angiogenesis will be assessed using high-resolution xray CT and immunohistomorphometry quantitatively. Mechanical properties of the repair tissue will be determined using an indentation test of the femoral head.
  
  
  CONCLUSIONS
  We envision that a deliverable or injectable bone graft substitute containing engineered stem cells and therapeutic growth factors will be developed through this proposed study and will provide a much needed treatment for ON.
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Trauma Service, University of Virginia School of Medicine, PO Box 800159, Charlottesville, VA 22908, USA. qc4q@hscmail.mcc.virginia.edu
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Cui
authors.forename: Edward A
authors.initials: EA
authors.lastname: Botchwey
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D055418:Bone Morphogenetic Protein 6 / Q000096:biosynthesis* / Q000235:genetics; D001861:Bone Regeneration; D058948:Cell Tracking; D002645:Chickens; D004195:Disease Models, Animal; D005271:Femur Head Necrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D007150:Immunohistochemistry; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D012107:Research Design; D033581:Stem Cell Transplantation; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D055418:Bone Morphogenetic Protein 6; D042461:Vascular Endothelial Growth Factor A