title: Heterogeneous Human Periodontal Ligament-Committed Progenitor and Stem Cell Populations Exhibit a Unique Cementogenic Property Under In Vitro and In Vivo Conditions.
abstract: An undesirable complication that arises during dental treatments is external apical-root resorption, which causes root-cementum and root-dentin loss. To induce de novo cementogenesis, stem cell therapy is required. Cementum-forming cells (cementoblasts) are known to be differentiated from periodontal-lineage mesenchymal stem cells (MSCs), which are derived from the dental follicle (DF) in developing tissues and the periodontal ligament (PDL) in adult tissues, but the periodontal-lineage MSC type that is optimal for inducing de novo cementogenesis remains unidentified, as does the method to isolate these cells from harvested tissues. Thus, we investigated the cementogenic potential of DF- and PDL-derived MSCs that were isolated by using two widely used cell-isolation methods: enzymatic digestion and outgrowth (OG) methods. DF- and PDL-derived cells isolated by using both methods proliferated actively, and all four isolated cell types showed MSC gene/protein expression phenotype and ability to differentiate into adipogenic and chondrogenic lineages. Furthermore, cementogenic-potential analysis revealed that all cell types produced alizarin red S-positive mineralized materials in in vitro cultures. However, PDL-OG cells presented unique cementogenic features, such as nodular formation of mineralized deposits displaying a cellular intrinsic fiber cementum-like structure, as well as a higher expression of cementoblast-specific genes than in the other cell types. Moreover, in in vivo transplantation experiments, PDL-OG cells formed cellular cementum-like hard tissue containing embedded osteocalcin-positive cells, whereas the other cells formed acellular cementum-like materials. Given that the root-cementum defect is likely regenerated through cellular cementum deposition, PDL-OG cell-based therapies might potentially facilitate the de novo cellular cementogenesis required for regenerating the root defect.
authors.affiliation: 1 Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry , Saitama, Japan .|2 Department of Developmental and Regenerative Dentistry, School of Life Dentistry at Tokyo, The Nippon Dental University , Tokyo, Japan .
authors.forename: Rei
authors.initials: R
authors.lastname: Shinagawa-Ohama
authors.affiliation: 2 Department of Developmental and Regenerative Dentistry, School of Life Dentistry at Tokyo, The Nippon Dental University , Tokyo, Japan .
authors.forename: Mai
authors.initials: M
authors.lastname: Mochizuki
authors.affiliation: 2 Department of Developmental and Regenerative Dentistry, School of Life Dentistry at Tokyo, The Nippon Dental University , Tokyo, Japan .
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tamaki
authors.affiliation: 1 Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry , Saitama, Japan .
authors.forename: Naoto
authors.initials: N
authors.lastname: Suda
authors.affiliation: 2 Department of Developmental and Regenerative Dentistry, School of Life Dentistry at Tokyo, The Nippon Dental University , Tokyo, Japan .
authors.forename: Taka
authors.initials: T
authors.lastname: Nakahara
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D025021:Cementogenesis; D003739:Dental Cementum / Q000166:cytology*; D003795:Dental Sac / Q000166:cytology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult
keywords: cell-isolation method; de novo cementogenesis; dental follicle; periodontal ligament; periodontal-lineage mesenchymal stem cell; stem cell therapy