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

S. C.N. Chang*, H. L. Chuang, Y. R. Chen, J. K. Chen, H. Y. Chung, Y. L. Lu, H. Y. Lin, C. L. Tai, J. Lou

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

113 Scopus citations

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.

Original languageEnglish
Pages (from-to)2013-2019
Number of pages7
JournalGene Therapy
Volume10
Issue number24
DOIs
StatePublished - 11 2003

Keywords

  • Bone regeneration
  • Stem cells
  • Tissue engineering

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