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


CONCLUSIONS
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.
Parrilla
Claudio
C
Department of Otolaryngology, School of Medicine, Catholic University of Sacred Heart, Rome, Italy. claudioparrilla@yahoo.com
Lattanzi
Wanda
W
Rita Fetoni
Anna
A
Bussu
Francesco
F
Pola
Enrico
E
Paludetti
Gaetano
G
D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use; D001861:Bone Regeneration / Q000235:genetics*; D003094:Collagen / Q000627:therapeutic use; D020405:Dermis / Q000473:pathology; D017886:Durapatite / Q000627:therapeutic use; D005347:Fibroblasts / Q000502:physiology / Q000637:transplantation*; D015316:Genetic Therapy / Q000379:methods*; D048091:Guided Tissue Regeneration / Q000379:methods*; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D008334:Mandible / Q000254:growth & development* / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds; D014157:Transcription Factors; D014161:Transduction, Genetic
D001672:Biocompatible Materials; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D014157:Transcription Factors; D003094:Collagen; D017886:Durapatite