title: Ex vivo gene therapy in autologous bone marrow stromal stem cells for tissue-engineered maxillofacial bone regeneration.
abstract: This study examines the clinical relevance of tissue engineering integrating gene therapy and polymer science to bone regeneration. Bilateral maxillary defects (3 x 1.2 cm(2)) in 20 miniature swine were bridged with a bioresorbable internal splint. Constructs were created using ex vivo adenovirus bone morphogenetic protein (BMP)-2-mediated gene transfer to the expanded bone marrow mesenchymal stem cells (MSCs) 7 days before implantation. Controls were performed using adenovirus beta-galactosidase. The BMP-2 cell/construct displayed white solid bone formation after 3 months. Meanwhile, the hematoxylin and eosin and Von Kossa stains demonstrated exhibited mature woven bone with good mineralization. Additionally, three-dimensional computer tomography imaging revealed a nearly complete infraorbital rim repair. Quantitative analysis demonstrated a significant difference (P<0.001) in bone formation. Finally, biomechanical testing revealed no statistically significant difference in the maximal compressive strength of new bone formed by BMP-2 cell constructs and the normal maxilla. The data evidenced de novo bone formation capable of sustaining axial compressive loads. The measurement results showed that ex vivo replication defective adenovirus-mediated human BMP-2 gene transfer to MSCs enhances autologous bone formation in the repair of maxillary defects.
authors.affiliation: Department of Plastic Surgery, Chang Gung Memorial Hospital, Kuei Shan Tao Yuan, Taiwan.
authors.forename: S C-N
authors.initials: SC
authors.lastname: Chang
authors.forename: H L
authors.initials: HL
authors.lastname: Chuang
authors.forename: Y R
authors.initials: YR
authors.lastname: Chen
authors.forename: J K
authors.initials: JK
authors.lastname: Chen
authors.forename: H-Y
authors.initials: HY
authors.lastname: Chung
authors.forename: Y-L
authors.initials: YL
authors.lastname: Lu
authors.forename: H-Y
authors.initials: HY
authors.lastname: Lin
authors.forename: C-L
authors.initials: CL
authors.lastname: Tai
authors.forename: J
authors.initials: J
authors.lastname: Lou
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001696:Biomechanical Phenomena; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001860:Bone Plates; D001861:Bone Regeneration / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008437:Maxilla / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D017154:Stromal Cells / Q000637:transplantation; D013556:Swine, Miniature; D023822:Tissue Engineering / Q000379:methods*; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta