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

Exp Cell Res. 2012 Mar 10;318(5):453-63. doi: 10.1016/j.yexcr.2012.01.008. Epub 2012 Jan 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis
  • Adolescent
  • Adult
  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / physiology
  • Adult Stem Cells / transplantation
  • Animals
  • Antigens, CD / metabolism
  • Bone Regeneration
  • Cell Proliferation
  • Chondrogenesis
  • Collagen Type I / metabolism
  • Dental Pulp / cytology*
  • Dental Pulp / metabolism
  • Flow Cytometry
  • Humans
  • Mice
  • Mice, SCID
  • Osteocalcin / metabolism
  • Osteogenesis
  • Phenotype
  • Stage-Specific Embryonic Antigens / metabolism*
  • Telomere Homeostasis
  • Tissue Scaffolds
  • Young Adult


  • Antigens, CD
  • Collagen Type I
  • Stage-Specific Embryonic Antigens
  • stage-specific embryonic antigen-4
  • Osteocalcin