Preliminary Studies of <i>in vivo</i> and <i>ex vivo</i> Implantations Accompanied by Transgenes

DOI
  • KURODA Shinji
    Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Japan
  • ENDO Masaki
    Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Japan
  • SAMEE Mayurach
    Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Japan
  • KONDO Hisatomo
    Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Japan
  • KASUGAI Shohei
    Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Japan

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Tissue engineering is the three-dimensional assembly over time of vital tissues and organs by a process involving cells, signals and extracellular matrix. Use of endogenous stem/progenitor cells combined into designed scaffolds with cytokines or growth factors for local delivery has been demonstrated as a discipline of more effective tissue engineering. However, several barriers to effective and safe local delivery of proteins in vivo have been identified because of their short life, high costing, difficulty to maintain full bioactivity and high-dose local delivery associated with both local and systemic toxicity. To overcome these barriers, gene therapy has emerged as an effective approach by which therapeutic proteins could be carried as genes. The preliminary studies introduced here are to explore the feasibility of our designed tissue engineering constructs using our modified gene activated matrix (GAM) with calcium phosphate and transgene for BMP-2 for in vivo, and periosteal cell culture with a collagen sponge and transgene for BMP-2/VEGF for ex vivo.<br>Our modified GAM tremendously bridged the bone defect with 12µg plasmid encoding for BMP-2 after 6 weeks, which was followed by mechanically strong bone replacement. And the second study implicated that the implanted collagen sponges harboring periosteal cells with BMP-2/VEGF contained the most alkaline phosphatase activity, enhancement of many of osteogenic gene expressions and prominent angiogenesis.

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