title: Stage-specific embryonic antigen-4 identifies human dental pulp stem cells.
abstract: Embryonic stem cell-associated antigens are expressed in a variety of adult stem cells as well as embryonic stem cells. In the present study, we investigated whether stage-specific embryonic antigen (SSEA)-4 can be used to isolate dental pulp (DP) stem cells. DP cells showed plastic adherence, specific surface antigen expression, and multipotent differentiation potential, similar to mesenchymal stem cells (MSC). SSEA-4+ cells were found in cultured DP cells in vitro as well as in DP tissue in vivo. Flow cytometric analysis demonstrated that 45.5% of the DP cells were SSEA-4+. When the DP cells were cultured in the presence of all-trans-retinoic acid, marked downregulation of SSEA-3 and SSEA-4 and the upregulation of SSEA-1 were observed. SSEA-4+ DP cells showed a greater telomere length and a higher growth rate compared to ungated and SSEA-4- cells. A clonal assay demonstrated that 65.5% of the SSEA-4+ DP cells had osteogenic potential, and the SSEA-4+ clonal DP cells showed multilineage differentiation potential toward osteoblasts, chondrocytes, and neurons in vitro. In addition, the SSEA-4+ DP cells had the capacity to form ectopic bone in vivo. Thus, our results suggest that SSEA-4 is a specific cell surface antigen that can be used to identify DP stem cells.
authors.affiliation: Department of Orthodontics, Okayama University Hospital, Kita-ku, Okayama 700-8525, Japan. kawanabe@md.okayama-u.ac.jp
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawanabe
authors.forename: Satoko
authors.initials: S
authors.lastname: Murata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fukushima
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yanagita
authors.forename: Emmy
authors.initials: E
authors.lastname: Yanagita
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurosaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamioka
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.forename: Takuo
authors.initials: T
authors.lastname: Kuboki
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamashiro
mesh_terms: D050156:Adipogenesis; D000293:Adolescent; D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism* / Q000502:physiology / Q000637:transplantation; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001861:Bone Regeneration; D049109:Cell Proliferation; D020219:Chondrogenesis; D024042:Collagen Type I / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D010641:Phenotype; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism*; D059505:Telomere Homeostasis; D054457:Tissue Scaffolds; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D024042:Collagen Type I; D055746:Stage-Specific Embryonic Antigens; C066584:stage-specific embryonic antigen-4; D015675:Osteocalcin