TY - JOUR
T1 - Stage-specific embryonic antigen-4 identifies human dental pulp stem cells
AU - Kawanabe, Noriaki
AU - Murata, Satoko
AU - Fukushima, Hiroaki
AU - Ishihara, Yoshihito
AU - Yanagita, Takeshi
AU - Yanagita, Emmy
AU - Ono, Mitsuaki
AU - Kurosaka, Hiroshi
AU - Kamioka, Hiroshi
AU - Itoh, Tomoo
AU - Kuboki, Takuo
AU - Yamashiro, Takashi
N1 - Funding Information:
The present study was supported by a Grant-in-Aid for Scientific Research (to N. Kawanabe) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by a Grant-in-Aid for Scientific Research (to T. Yamashiro) from the Japan Society for the Promotion of Science, Japan .
PY - 2012/3/10
Y1 - 2012/3/10
N2 - 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.
AB - 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.
KW - Adult stem cells
KW - Clonal assays
KW - Human dental pulp cells
KW - Multipotential differentiation
KW - Stage-specific embryonic antigen-4
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U2 - 10.1016/j.yexcr.2012.01.008
DO - 10.1016/j.yexcr.2012.01.008
M3 - Article
C2 - 22266579
AN - SCOPUS:84857039921
SN - 0014-4827
VL - 318
SP - 453
EP - 463
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 5
ER -