title: Loss of proliferation and differentiation capacity of aged human periodontal ligament stem cells and rejuvenation by exposure to the young extrinsic environment.
abstract: The application of periodontal ligament stem cells (PDLSCs) may be effective for periodontal regenerative therapy. As tissue regenerative potential may be negatively regulated by aging, whether aging and its microenvironment modify human PDLSCs remains a question. In this study, we compared the proliferation and differentiation capacity of PDLSCs obtained from young and aged donors. Then, we exposed aged PDLSCs to young periodontal ligament cell-conditioned medium (PLC-CM), and young PDLSCs were exposed to aged PLC-CM. Morphological appearance, colony-forming assay, cell cycle analysis, osteogenic and adipogenic induction media, gene expression of cementoblast phenotype, and in vivo differentiation capacities of PDLSCs were evaluated. PDLSCs obtained from aged donors exhibited decreased proliferation and differentiation capacity when compared with those from young donors. Young PLC-CM enhanced the proliferation and differentiation capacity of PDLSCs from aged donors. Aged PDLSCs induced by young PLC-CM showed enhanced tissue-regenerative capacity to produce cementum/periodontal ligament-like structures, whereas young PDLSCs induced by aged PLC-CM transplants mainly formed connective tissues. To our knowledge, this is the first study to mimic the developmental microenvironment of PDLSCs in vitro, and our data suggest that age influences the proliferation and differentiation potential of human PDLSCs, and that the activity of human PDLSCs can be modulated by the extrinsic microenvironment.
authors.affiliation: Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Ma
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Yinzhong
authors.initials: Y
authors.lastname: Duan
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000375:Aging / Q000378:metabolism*; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003114:Colony-Forming Units Assay; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology* / Q000637:transplantation; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D015675:Osteocalcin