Stage-specific embryonic antigen-4 identifies human dental pulp stem cells

Noriaki Kawanabe, Satoko Murata, Hiroaki Fukushima, Yoshihito Ishihara, Takeshi Yanagita, Emmy Yanagita, Mitsuaki Ono, Hiroshi Kurosaka, Hiroshi Kamioka, Tomoo Itoh, Takuo Kuboki, Takashi Yamashiro

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)453-463
Number of pages11
JournalExperimental Cell Research
Issue number5
Publication statusPublished - Mar 10 2012


  • Adult stem cells
  • Clonal assays
  • Human dental pulp cells
  • Multipotential differentiation
  • Stage-specific embryonic antigen-4

ASJC Scopus subject areas

  • Cell Biology


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