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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

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 CD24 pos cells exhibit delayed mineralization and reduced capacity for adipocyte differentiation. RNAseq analysis of CD24 pos and CD24 neg BMSCs identified a limited number of genes with increased expression in CD24 pos cells that are associated with cell adhesion, motility, and extracellular matrix. Downregulated genes are associated with cell cycle regulation, and biological assays revealed that CD24 pos 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
Pages (from-to)325-336
Number of pages12
JournalStem Cells and Development
Volume30
Issue number6
DOIs
Publication statusPublished - 16 Mar 2021

Bibliographical note

Funding Information:
This work was supported by the Dutch Institute for Regenerative medicine (NIRM: grant no. FES0908), Erasmus MC Stem Cell and Regenerative Medicine Institute and Erasmus Medical Center (EMC-MM-01-39-02), and European Commission FP7 Program INTERBONE Grant PIRSES-GA-2011–295181. This work was also supported in part by NIH grant R01 AR049069 (to AJvW).

Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.

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