Stage-specific embryonic antigen 4 in Wharton's jelly-derived mesenchymal stem cells is not a marker for proliferation and multipotency

Tissue Eng Part A. 2014 Apr;20(7-8):1314-24. doi: 10.1089/ten.TEA.2013.0333. Epub 2014 Mar 14.

Abstract

Background: Umbilical cord Wharton's jelly (WJ) is a rich source of mesenchymal stem cells (MSCs) similar to bone marrow (BM) and adipose tissues. Stage-specific embryonic antigen (SSEA)4 has been reported as a stem cell marker in BM-derived MSCs, but whether SSEA4(+) cells have growth and differentiation advantages over SSEA4(-) cells remains controversial. To gain insight into the role of SSEA4, we studied SSEA4(+) cells in WJ-derived MSCs (WJ-MSCs).

Methods: WJ-MSCs were collected by the explant (WJe-MSCs) or collagenase methods (WJc-MSCs) and analyzed by flow cytometry and reverse-transcription polymerase chain reaction (RT-PCR). To evaluate whether culture conditions influenced the SSEA4 expression, WJe-MSCs were cultured in the medium supplemented with different fetal bovine serum (FBS) concentrations.

Results: SSEA4 was expressed for a long-term culture. In contrast, SSEA3(+) disappeared rapidly in early passages of the culture. The incidence of SSEA4(+) and SSEA3(+) cells was similar between WJe-MSCs and WJc-MSCs at passages P0-P9, except for transient depletion of SSEA4 expression in early passages of WJe-MSCs. These were CD73(+)CD105(+) cells that express embryonic stem cell markers detected by RT-PCR. No differences in growth and differentiation ability of osteocytes and adipocytes were observed between the sorted SSEA4(+) cells and SSEA4(-) cells. Further, SSEA4 expression in WJe-MSCs was significantly correlated with FBS concentration in the culture medium.

Discussion: SSEA4, which may display altered expression profiles in response to culture conditions, may not be an essential marker of WJ-MSC multipotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Antigens, Tumor-Associated, Carbohydrate / metabolism
  • Biomarkers
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • Cell Proliferation
  • Flow Cytometry
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / metabolism*
  • Osteogenesis
  • Stage-Specific Embryonic Antigens / metabolism*
  • Umbilical Cord / cytology
  • Wharton Jelly / cytology*

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Biomarkers
  • Stage-Specific Embryonic Antigens
  • stage-specific embryonic antigen-3
  • stage-specific embryonic antigen-4