Ex vivo gene therapy using autologous dermal fibroblasts expressing hLMP3 for rat mandibular bone regeneration

Head Neck. 2010 Mar;32(3):310-8. doi: 10.1002/hed.21185.

Abstract

Background: Implantation of autologous skin fibroblasts transduced ex vivo with a replication-defective adenoviral vector, carrying the LIM mineralization protein-3 (Ad-LMP-3), and adsorbed on a hydroxyapatite/collagen (HA/COL) scaffold.

Methods: Twenty-seven Wistar rats were used. A 5- x 5-mm full-thickness defect was created in the exposed mandible. All animals were randomized into 3 experimental groups: (1) autologous dermal fibroblasts transduced with Ad-LMP-3 and adsorbed on the HA/COL; (2) nontransduced dermal fibroblasts adsorbed on the HA/COL scaffold; and (3) HA/COL scaffold without cells. Three-dimensional micro-CT (3DmicroCT or 3DmuCT) and histological analysis were performed.

Results: Efficient neoosteogenesis was observed in animals treated with LMP-3-expressing cells (group 1) as soon as 4 weeks after surgery. Conversely, nonsignificant bone formation was detected in control animals (groups 2 and 3) at all time points tested.

Conclusion: These results suggest that the experimental approach based on transplantation of genetically modified autologous cells could provide an alternative treatment for cranio-maxillo-facial defects. Nonetheless, additional data from the study on larger bone defects must follow to foresee a clinical application in the near future.

MeSH terms

  • Animals
  • Biocompatible Materials / therapeutic use
  • Bone Regeneration / genetics*
  • Collagen / therapeutic use
  • Dermis / pathology
  • Durapatite / therapeutic use
  • Fibroblasts / physiology
  • Fibroblasts / transplantation*
  • Genetic Therapy / methods*
  • Guided Tissue Regeneration / methods*
  • Homeodomain Proteins*
  • LIM-Homeodomain Proteins
  • Mandible / growth & development*
  • Mandible / pathology
  • Osteogenesis / genetics
  • Rats
  • Rats, Wistar
  • Tissue Scaffolds
  • Transcription Factors
  • Transduction, Genetic

Substances

  • Biocompatible Materials
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lhx3 protein
  • Transcription Factors
  • Collagen
  • Durapatite