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Adenovirus Encoding Human Platelet-Derived Growth Factor-B Delivered to Alveolar Bone Defects Exhibits Safety and Biodistribution Profiles Favorable for Clinical Use

Cited 66 time in Web of Science Cited 66 time in Scopus
Authors
Chang, Po-Chun; Cirelli, Joni A.; Jin, Qiming; Seol, Yang-Jo; Sugai, James V.; D'Silva, Nisha J.; Danciu, Theodora E.; Chandler, Lois A.; Sosnowski, Barbara A.; Giannobile, William V.
Issue Date
2009-05
Publisher
Mary Ann Liebert
Citation
Human Gene Therapy. 20(5), 486-496
Abstract
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 AdPDGF-B at 5.5 108 or 5.5 109 plaque-forming units=ml.
The regenerative response was confirmed histologically. Gross clinical observations, hematology, and blood
chemistries were monitored to evaluate systemic involvement. Bioluminescence and quantitative polymerase
chain reaction were used to assess 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 possible use in human clinical studies.
ISSN
1043-0342
Language
English
URI
http://hdl.handle.net/10371/68611
DOI
https://doi.org/10.1089/hum.2008.114
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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