Authors:
Chang PC, Cirelli JA, Jin Q, Seol YJ, Sugai JV, D'Silva NJ, Danciu TE, Chandler LA, Sosnowski BA, & Giannobile WV
Summary:
Platelet-derived growth factor (PDGF) gene therapy offers promise for tissue engineering of tooth-supporting alveolar bone defects. To date, limited information exists regarding the safety profile and systemic biodistribution of PDGF gene therapy vectors when delivered locally to periodontal osseous defects. The aim of this preclinical study was to determine the safety profile of adenovirus encoding the PDGF-B gene (AdPDGF-B) delivered in a collagen matrix to periodontal lesions. Standardized alveolar bone defects were created in rats, followed by delivery of matrix alone or containing 5.5x108 or 5.5x109 pfu/ml AdPDGF-B. The regenerative response was confirmed histologically. Gross clinical observations, hematology and blood chemistries were monitored to evaluate systemic involvement. Bioluminescence and QPCR were utilized for assessing vector biodistribution. No significant histopathological changes were noted during the investigation. Minor alterations in specific hematological and blood chemistries were seen, however, most parameters were within the normal range for all groups. Bioluminescence analysis revealed vector distribution at the axillary lymph nodes during the first 2 weeks with subsequent return to baseline levels. AdPDGF-B was well-contained within the localized osseous defect area without viremia or distant organ involvement. These results indicate that AdPDGF-B delivered in a collagen matrix exhibits acceptable safety profiles for consideration of human clinical studies.
Source:
Human Gene Therapy; (02/06/09)