title: Bone Marrow Mesenchymal Stem Cells Expressing Baculovirus-Engineered Bone Morphogenetic Protein-7 Enhance Rabbit Posterolateral Fusion.
abstract: Previous studies have suggested that bone marrow-derived mesenchymal stem cells (BMDMSCs) genetically modified with baculoviral bone morphogenetic protein-2 (Bac-BMP-2) vectors could achieve successful fusion in a femur defect model or in a spinal fusion model. In this study, BMDMSCs expressing BMP-7 (Bac-BMP-7-BMDMSCs) were generated. We hypothesized that Bac-BMP-7-BMDMSCs could secrete more BMP-7 than untransduced BMDMSCs in vitro and achieve spinal posterolateral fusion in a rabbit model. Eighteen rabbits underwent posterolateral fusion at L4-5. Group I (n = 6) was implanted with collagen-β-tricalcium phosphate (TCP)-hydroxyapatite (HA), Group II (n = 6) was implanted with collagen-β-TCP-HA plus BMDMSCs, and Group III (n = 6) was implanted with collagen-β-TCP-HA plus Bac-BMP-7-BMDMSCs. In vitro production of BMP-7 was quantified with an enzyme-linked immunosorbent assay (ELISA). Spinal fusion was examined using computed tomography (CT), manual palpation, and histological analysis. ELISA demonstrated that Bac-BMP-7-BMDMSCs produced four-fold to five-fold more BMP-7 than did BMDMSCs. In the CT results, 6 fused segments were observed in Group I (50%, 6/12), 8 in Group II (67%, 8/12), and 12 in Group III (100%, 12/12). The fusion rate, determined by manual palpation, was 0% (0/6) in Group I, 0% (0/6) in Group II, and 83% (5/6) in Group III. Histology showed that Group III had more new bone and matured marrow formation. In conclusion, BMDMSCs genetically transduced with the Bac-BMP-7 vector could express more BMP-7 than untransduced BMDMSCs. These Bac-BMP-7-BMDMSCs on collagen-β-TCP-HA scaffolds were able to induce successful spinal fusion in rabbits.
authors.affiliation: Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan. jcl1265@adm.cgmh.org.tw.
authors.forename: Jen-Chung
authors.initials: JC
authors.lastname: Liao
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D001854:Bone Marrow Cells / Q000166:cytology*; D055419:Bone Morphogenetic Protein 7 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D013123:Spinal Fusion; D013124:Spinal Injuries / Q000473:pathology / Q000628:therapy; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D055419:Bone Morphogenetic Protein 7; D002130:Calcium Phosphates; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate
keywords: baculovirus; bone marrow stem cell; bone morphogenetic protein 7; rabbit; spinal fusion