Characterization of the Enhanced Bone Regenerative Capacity of Human Periodontal Ligament Stem Cells Engineered to Express the Gene Encoding Bone Morphogenetic Protein 2

• Published in: Tissue engineering. Part A 2014-08, Vol.20 (15-16), p.2189-2199
• Main Authors: Jung, Im-Hee, Lee, Si-Ho, Jun, Choong-Man, Oh, Namsik, Yun, Jeong-Ho
• Format: Article
• Language: English
• Subjects: Adenoviridae - metabolism; Adenovirus; Adult; Animals; Biomarkers - metabolism; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 2 - metabolism; Bone Regeneration; Bones; Calcification, Physiologic; Cell Survival; Genetics; Green Fluorescent Proteins - metabolism; Humans; Immunohistochemistry; Ligaments; Mice, Inbred BALB C; Mice, Nude; Original; Original Articles; Osteogenesis; Periodontal Ligament - cytology; Proteins; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Stem cells; Stem Cells - cytology; Tissue engineering; Tissue Engineering - methods; Transduction, Genetic; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2013.0648

Human periodontal ligament stem cells (hPDLSCs) are considered an appropriate cell source for therapeutic strategies. The aims of this study were to investigate the sustainability of bone morphogenetic protein 2 (BMP2) secretion and the bone regenerative capacity of hPDLSCs that had been genetically modified to express the gene encoding BMP2 ( BMP2 ). hPDLSCs isolated from healthy third molars were transduced using replication-deficient recombinant adenovirus (rAd) encoding BMP2 (hPDLSCs/rAd-BMP2), and the cellular characteristics and osteogenic potentials of hPDLSCs/rAd-BMP2 were analyzed both in vitro and in vivo . hPDLSCs/rAd-BMP2 successfully secreted BMP2, formed colonies, and expressed immunophenotypes similar to their nontransduced counterparts. As to their osteogenic potential, hPDLSCs/rAd-BMP2 formed greater mineralized nodules and exhibited significantly higher levels of expression of BMP2 and the gene encoding alkaline phosphatase, and formed more and better quality bone than other hPDLSC-containing or recombinant human BMP2-treated groups, being localized at the initial site until 8 weeks. The findings of the present study demonstrate that hPDLSCs/rAd-BMP2 effectively promote osteogenesis not only in vitro but also in vivo . The findings also suggest that hPDLSCs can efficiently carry and deliver BMP2, and that hPDLSCs/rAd-BMP2 could be used in an attractive novel therapeutic approach for the regeneration of deteriorated bony defects.