https://scholars.lib.ntu.edu.tw/handle/123456789/464022
標題: | Large-scale bicortical skull bone regeneration using ex vivo replication-defective adenoviral-mediated bone morphogenetic protein-2 gene-transferred bone marrow stromal cells and composite biomaterials | 作者: | Chang, S.C.-N. Lin, T.-M. Chung, H.-Y. Chen, P.K.-T. Lin, F.-H. Lou, J. Jeng, L.-B. Lin, Feng-Huei |
關鍵字: | Bone marrow mesenchymal stem cells; E1A-deleted adenovirus; Ex vivo gene therapy | 公開日期: | 2009 | 卷: | 65 | 期: | 6 SUPPL. 1 | 來源出版物: | Neurosurgery | 摘要: | OBJECTIVE: Bone marrow stromal cells (BMSCs) have great potential in bone repair. We developed an animal model to test the hypothesis that ex vivo gene transfer of human bone morphogenetic protein (BMP)-2 to BMSCs via a replication-defective (E1A-deleted) adenovirus vector (AdV) with appropriate biopolymers would enhance autologous bone formation during repair of a large-scale skull defect. METHODS: Eighteen miniature swine were treated with AdV BMP-2-transduced BMSCs in biopolymer (group 1), BMSCs in biopolymer (group 2), or biopolymer alone (group 3). After 6 months, the swine were killed, and the skull repair was examined by gross pictures, histology, 3-dimensional computed tomography, and biomechanical study. RESULTS: Group 1 showed complete solid bone formation after 6 months, and hematoxylin and eosin staining demonstrated the presence of mature, woven, well-mineralized bone. Computed tomography showed wholesome repair of the skull defect. Statistical analysis demonstrated a significant difference in bone thickness between groups 1 and 2. Biomechanical testing showed a statistically significant difference in the stiffness of new bone formed in group 1 compared with group 2. CONCLUSION: The Ad5 E1A-deleted AdV may be the optimal starting vector in ex vivo gene therapy for benign skeletal diseases. Additionally, the use of the gelatin/tricalcium phosphate ceramic/glutaraldehyde biopolymer with AdV BMP-2 gene transfer strongly enhances the bony healing of critical-size bicortical craniofacial defects. This method can be used by modifying the delivery of constructs to malunion treatment, in regional osteoporosis therapy, and spinal fusion. ? 2009 by the Congress of Neurological Surgeons. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/464022 | DOI: | 10.1227/01.NEU.0000345947.33730.91 | SDG/關鍵字: | adenovirus vector; biopolymer; bone morphogenetic protein 2; calcium phosphate ceramic; gelatin; glutaraldehyde; Adenovirus 5; animal experiment; animal model; animal tissue; article; autologous bone marrow transplantation; biomechanics; biomedical engineering; bone mineralization; bone regeneration; bone strength; controlled study; ex vivo gene transfer; female; fracture healing; histology; minipig; nonhuman; ossification; priority journal; skull defect; stroma cell; Adenoviridae; Animals; Biocompatible Materials; Biopolymers; Bone Marrow Transplantation; Bone Morphogenetic Protein 2; Bone Regeneration; Bone Substitutes; Calcium Phosphates; Cells, Cultured; Craniotomy; Female; Gene Transfer Techniques; Genetic Vectors; Glutaral; Models, Animal; Skull; Stromal Cells; Sus scrofa; Treatment Outcome; Virus Replication; Wound Healing |
顯示於: | 醫學工程學研究所 |
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