Characterization of the enhanced bone regenerative capacity of human periodontal ligament stem cells engineered to express the gene encoding bone morphogenetic protein 2.
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.
Department of Dentistry, School of Medicine, Inha University , Incheon, Republic of Korea.
Im-Hee
IH
Jung
Si-Ho
SH
Lee
Choong-Man
CM
Jun
Namsik
N
Oh
Jeong-Ho
JH
Yun
D000256:Adenoviridae / Q000378:metabolism; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D001861:Bone Regeneration; D002113:Calcification, Physiologic; D002470:Cell Survival; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010012:Osteogenesis; D010513:Periodontal Ligament / Q000166:cytology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C485184:enhanced green fluorescent protein; C499469:recombinant human bone morphogenetic protein-2; D049452:Green Fluorescent Proteins