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Ex vivo gene therapy in autologous bone marrow stromal stem cells for tissue-engineered maxillofacial bone regeneration

Gene Therapy volume 10, pages 2013–2019 (2003)Cite this article

Abstract

This study examines the clinical relevance of tissue engineering integrating gene therapy and polymer science to bone regeneration. Bilateral maxillary defects (3 × 1.2 cm2) 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 β-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.

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Acknowledgements

We would like to thank Professor Sing Kai Lo, Institute for International Health, University of Sydney for the statistical work in this manuscript. We wish to thank Dr Lun-Jou Lo and the Medical Imaging Laboratory for providing the CT imaging processing and measurement, and Dr Richard A Robb, PhD, Biomedical Imaging Resource, Mayo Foundation, Rochester, MN, USA, for providing the Analyze program. This research was supported by a Chang Gung Memorial Hospital Grant (CTRP008).

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Authors and Affiliations

  1. Department of Plastic Surgery, Chang Gung Memorial Hospital, Kuei Shan Tao Yuan, Taiwan

    S C-N Chang & Y R Chen

  2. Division of Neurosurgery, Department of Surgery, HsinChu Mackay Memorial Hospital, Hsinchu City, Taiwan

    H L Chuang

  3. Department of Physiology, Chang Gung University, Kwei-Shan TaoYuan, Taiwan

    J K Chen, H-Y Chung, Y-L Lu & H-Y Lin

  4. Department of Orthopedic Surgery, Biomechanics Center, Chang Gung Memorial Hospital, Kuei Shan Tao Yuan, Taiwan

    C-L Tai

  5. Department of Orthopedic Surgery, Washington University Medical School, One Barnes Hospital Plaza, St Louis, MO, USA

    J Lou

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  1. S C-N Chang
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Chang, SN., Chuang, H., Chen, Y. et al. Ex vivo gene therapy in autologous bone marrow stromal stem cells for tissue-engineered maxillofacial bone regeneration. Gene Ther 10, 2013–2019 (2003). https://doi.org/10.1038/sj.gt.3302106

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