title: Mesenchymal stem cells with increased stromal cell-derived factor 1 expression enhanced fracture healing.
abstract: Treatment of critical size bone defects pose a challenge in orthopedics. Stem cell therapy together with cytokines has the potential to improve bone repair as they cause the migration and homing of stem cells to the defect site. However, the engraftment, participation, and recruitment of other cells within the regenerating tissue are important. To enhance stem cell involvement, this study investigated overexpression of stem cells with stromal cell-derived factor 1 (SDF-1) using an adenovirus. We hypothesized that these engineered cells would effectively increase the migration of native cells to the site of fracture, enhancing bone repair. Before implantation, we showed that SDF-1 secreted by transfected cells increased the migration of nontransfected cells. In a rat defect bone model, bone marrow mesenchymal stem cells overexpressing SDF-1 showed significantly (p=0.003) more new bone formation within the gap and less bone mineral loss at the area adjacent to the defect site during the early bone healing stage. In conclusion, SDF-1 was shown to play an important role in accelerating fracture repair and contributing to bone repair in rat models, by recruiting more host stem cells to the defect site and encouraging osteogenic differentiation and production of bone.
authors.affiliation: Division of Surgery and Interventional Sciences, Institute of Orthopaedics and Musculoskeletal Science, The John Scales Centre for Biomedical Engineering, University College London , Royal National Orthopaedic Hospital, Stanmore, United Kingdom .
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Ho
authors.forename: Anita
authors.initials: A
authors.lastname: Sanghani
authors.forename: Jia
authors.initials: J
authors.lastname: Hua
authors.forename: Melanie
authors.initials: M
authors.lastname: Coathup
authors.forename: Priya
authors.initials: P
authors.lastname: Kalia
authors.forename: Gordon
authors.initials: G
authors.lastname: Blunn
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D005264:Femoral Fractures / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D017102:Fracture Healing / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D054377:Chemokine CXCL12