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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
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chang, Po-Chun | - |
dc.contributor.author | Cirelli, Joni A. | - |
dc.contributor.author | Jin, Qiming | - |
dc.contributor.author | Seol, Yang-Jo | - |
dc.contributor.author | Sugai, James V. | - |
dc.contributor.author | D'Silva, Nisha J. | - |
dc.contributor.author | Danciu, Theodora E. | - |
dc.contributor.author | Chandler, Lois A. | - |
dc.contributor.author | Sosnowski, Barbara A. | - |
dc.contributor.author | Giannobile, William V. | - |
dc.date.accessioned | 2010-07-13T07:21:14Z | - |
dc.date.available | 2010-07-13T07:21:14Z | - |
dc.date.issued | 2009-05 | - |
dc.identifier.citation | Human Gene Therapy. 20(5), 486-496 | en |
dc.identifier.issn | 1043-0342 | - |
dc.identifier.uri | https://hdl.handle.net/10371/68611 | - |
dc.description.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. | en |
dc.description.sponsorship | The authors thank Anna Colvig for performing hematological
and clinical chemical examinations, Amanda Welton for assistance with bioluminescence, Dr. John E. Wilkinson for assistance with veterinary pathology, and Christopher Strayhorn for assistance with histological processing. This study was supported in part by grants from the AO Foundation (Davos, Switzerland) and NIH=NIDCR R01- DE13397 | en |
dc.language.iso | en | en |
dc.publisher | Mary Ann Liebert | en |
dc.title | Adenovirus Encoding Human Platelet-Derived Growth Factor-B Delivered to Alveolar Bone Defects Exhibits Safety and Biodistribution Profiles Favorable for Clinical Use | en |
dc.type | Article | en |
dc.identifier.doi | 10.1089/hum.2008.114 | - |
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