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Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty

Gene Therapy volumeĀ 15,Ā pages 1469ā€“1477 (2008)Cite this article

Abstract

The regeneration of the periodontal attachment apparatus remains clinically challenging because of the involvement of three tissue types and the complexity of their relationship. Human recombinant bone morphogenic protein-2 (rhBMP-2) can accelerate the regeneration of bone and cementum and the insertion of periodontal ligament fibers but may lead to a deranged periodontal relationship, ankylosis and root resorption.

This study evaluated a novel approach to regeneration of the periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication-defective adenovirus to express the BMP-2 gene and Pluronic F127 (PF127). Twenty-four periodontal defects were surgically created in 12 New Zealand white rabbits and randomly assigned to three experimental groups with MSCs: the advBMP-2 group; the advĪ²gal group; the MSC group and one control group: PF127 only. The regenerated periodontal attachment apparatus was assessed histologically and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis.This approach regenerated not only cementum with Sharpey's fiber insertion, but also statistically significant quantities of bone, re-establishing a more normal relationship among the components of the regenerated periodontal attachment apparatus, which is beneficial for the maintenance of periodontal health.Ex vivo gene transfer using stem cells as vectors may provide an advantage of slower BMP-2 release, increasing cementogenesis. There is regeneration of the periodontal attachment apparatus, whereas direct usage of the protein (rhBMP-2) yields unhinged periodontal relationship. Thus, this approach may represent an alternative means for periodontal alveolar bone graft in clinical settings.

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Acknowledgements

We thank professor Sing Kai Lo, Institute for International Health, University of Sydney, for the statistical work related to this work. We also thank professor Jueren Lou, Shanghai Institute of Biological Products, China National Biotec Group, for the gift of adenovirus. We thank Dr Lun-Jou Lo and the Medical Imaging Laboratory for performing the CT image processing and measurement and Dr Richard A Robb, PhD, Biomedical Imaging Resource, Mayo Foundation, Rochester, Minnesota, for using the Analyze program. This research was supported by the National Science Council Foundation, Taiwan, contract numbers NSC 91-2314-B-182A-115, NSC 92-2314-B-182A-059 and NSC 93-2314-B-182A-002.

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Authors and Affiliations

  1. Department of Dentistry, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan

    Y-L ChenĀ &Ā C-S Huang

  2. Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan

    P K-T Chen

  3. Department of Surgery, China Medical University Hospital, Taichung, Taiwan

    L-B Jeng

  4. School of Medicine, China Medical University, Taichung, Taiwan

    L-B JengĀ &Ā S C-N Chang

  5. Department of Anesthesiology, E-Da Hospital, Kaohsiung, Taiwan

    L-C Yang

  6. Department of Biological Science and Technology, College of Medical Sciences, I-Shou University, Kaohsiung, Taiwan

    L-C Yang

  7. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

    H-Y Chung

  8. Department of Plastic Surgery, China Medical University Hospital, Taichung, Taiwan

    S C-N Chang

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Correspondence to S C-N Chang.

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Chen, YL., Chen, PT., Jeng, LB. et al. Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty. Gene Ther 15, 1469ā€“1477 (2008). https://doi.org/10.1038/gt.2008.131

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  • DOI: https://doi.org/10.1038/gt.2008.131

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