Cell Surface Glycoprotein CD24 Marks Bone Marrow-Derived Human Mesenchymal Stem/Stromal Cells with Reduced Proliferative and Differentiation Capacity in Vitro

Jeroen Van De Peppel, Gerben J. Schaaf, Adriana Arruda Matos, Yuan Guo, Tanja Strini, Wenda Verschoor, Amel Dudakovic, Andre J van Wijnen, Johannes P.T.M. Van Leeuwen

Research output: Contribution to journalArticlepeer-review

Abstract

Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) are fundamental to bone regenerative therapies, tissue engineering, and postmenopausal osteoporosis. Donor variation among patients, cell heterogeneity, and unpredictable capacity for differentiation reduce effectiveness of BMSCs for regenerative cell therapies. The cell surface glycoprotein CD24 exhibits the most prominent differential expression during osteogenic versus adipogenic differentiation of human BMSCs. Therefore, CD24 may represent a selective biomarker for subpopulations of BMSCs with increased osteoblastic potential. In undifferentiated human BMSCs, CD24 cell surface expression is variable among donors (range: 2%-10%) and increased by two to fourfold upon osteogenic differentiation. Strikingly, FACS sorted CD24pos cells exhibit delayed mineralization and reduced capacity for adipocyte differentiation. RNAseq analysis of CD24pos and CD24neg BMSCs identified a limited number of genes with increased expression in CD24pos cells that are associated with cell adhesion, motility, and extracellular matrix. Downregulated genes are associated with cell cycle regulation, and biological assays revealed that CD24pos cells have reduced proliferation. Hence, expression of the cell surface glycoprotein CD24 identifies a subpopulation of human BMSCs with reduced capacity for proliferation and extracellular matrix mineralization. Functional specialization among BMSCs populations may support their regenerative potential and therapeutic success by accommodating cell activities that promote skeletal tissue formation, homeostasis, and repair.

Original languageEnglish (US)
Pages (from-to)325-336
Number of pages12
JournalStem Cells and Development
Volume30
Issue number6
DOIs
StatePublished - Mar 2021

Keywords

  • bone
  • bone marrow mesenchymal stem cells
  • differentiation
  • osteoblast

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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