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

被引：35

作者：

Chang, Sophia Chia-Ning ^{[2
,3
]}

Lin, Tsung-Min ^{[4
]}

Chung, Hui-Ying ^{[4
]}

Chen, Philip Kuo-Ting ^{[5
,6
]}

Lin, Feng-Huei ^{[7
]}

Lou, Jeuren ^{[8
]}

Jeng, Long-Bin ^{[1
,2
]}

机构：

[1] China Med Univ Hosp, Dept Surg, Taichung 404, Taiwan

[2] China Med Univ, Sch Med, Taichung, Taiwan

[3] China Med Univ Hosp, Dept Plast Surg, Taichung 404, Taiwan

[4] China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan

[5] Chang Gung Mem Hosp, Dept Plast Surg, Tao Yuan, Taiwan

[6] Chang Gung Univ, Coll Med, Tao Yuan, Taiwan

[7] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan

[8] Shanghai Inst Biol Prod, Shanghai, Peoples R China

来源：

NEUROSURGERY | 2009年 / 65卷 / 06期

关键词：

Bone marrow mesenchymal stem cells; E1A-deleted adenovirus; Ex vivo gene therapy; STEM-CELLS; IN-VITRO; THERAPY; REPAIR; DIFFERENTIATION; TISSUE; EXPRESSION; CARTILAGE; DELIVERY; RECONSTRUCTION;

D O I：

10.1227/01.NEU.0000345947.33730.91

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

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.

引用

页码：75 / 82

页数：8

共 64 条

[1] EXPRESSION OF HUMAN BONE MORPHOGENETIC PROTEINS-2 OR PROTEINS-4 IN MURINE MESENCHYMAL PROGENITOR C3H10T1/2 CELLS INDUCES DIFFERENTIATION INTO DISTINCT MESENCHYMAL CELL LINEAGES [J].