title: Evaluation of In Vivo Osteogenic Potential of Bone Morphogenetic Protein 2-Overexpressing Human Periodontal Ligament Stem Cells Combined with Biphasic Calcium Phosphate Block Scaffolds in a Critical-Size Bone Defect Model.
abstract: Human periodontal ligament stem cells (hPDLSCs) are considered potential cellular carriers for gene delivery in the field of tissue regeneration. This study tested the osseoregenerative potential of hPDLSCs transduced with replication-deficient recombinant adenovirus (rAd) containing the gene encoding bone morphogenetic protein-2 (BMP2; hPDLSCs/rAd-BMP2) in both in vivo and in vitro osteogenic environments. After the optimal condition for rAd-mediated transduction was determined, hPDLSCs were transduced to express BMP2. In vivo bone formation was evaluated in a critical-size rat calvarial bone defect model that more closely mimics the harsher in vivo milieu for bone regeneration than subcutaneous transplantation model. As support materials for bone regeneration, block-type biphasic calcium phosphate (BCP) scaffolds were combined with hPDLSCs and/or BMP2 and transplanted into critical-size bone defects in rats. Experimental groups were as follows: BCP scaffold control (group 1 [Gr1]), scaffold containing recombinant human BMP2 (rhBMP2; group 2 [Gr2]), scaffold loaded with normal hPDLSCs (group 3 [Gr3]), scaffold combined with both normal hPDLSCs and rhBMP2 (group 4 [Gr4]), and scaffold loaded with hPDLSCs transduced with rAd-BMP2 (hPDLSCs/rAd-BMP2; group 5 [Gr5]). Our data showed that new bone formation was highest in Gr2. Less mineralization was observed in Gr3, Gr4, and Gr5 in which hPDLSCs were transplanted. In vitro transwell assay demonstrated that hPDLSCs exert an inhibitory activity on BMP2-induced osteogenic differentiation. Our findings suggest that the in vivo bone regenerative potential of BMP2-overexpressing hPDLSCs could be compromised in a critical-size rat calvarial bone defect model. Thus, further investigations are required to elucidate the underlying mechanisms and to develop efficient techniques for improved tissue regeneration.
authors.affiliation: 1 Translational Research Center and Inha Research Institute for Medical Sciences, Inha University School of Medicine , Incheon, Republic of Korea.
authors.forename: TacGhee
authors.initials: T
authors.lastname: Yi
authors.affiliation: 2 Division of Periodontology, Department of Dentistry, Inha University School of Medicine , Incheon, Republic of Korea.
authors.forename: Choong-Man
authors.initials: CM
authors.lastname: Jun
authors.affiliation: 3 Department of Life Sciences, Pohang University of Science and Technology (POSTECH) , Pohang, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: 4 Department of Periodontology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University , Jeonju, Republic of Korea.|5 Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital , Jeonju, Republic of Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Yun
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006882:Hydroxyapatites / Q000494:pharmacology*; D007150:Immunohistochemistry; D010012:Osteogenesis / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology*; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014161:Transduction, Genetic
chemical_list: D055396:Bone Morphogenetic Protein 2; D006882:Hydroxyapatites; C074950:hydroxyapatite-beta tricalcium phosphate