Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Stem Cells Dev. 2021 Mar;30(6):325-336. doi: 10.1089/scd.2021.0027.
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 cells exhibit delayed mineralization and reduced capacity for adipocyte differentiation. RNAseq analysis of CD24 and CD24 BMSCs identified a limited number of genes with increased expression in CD24 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 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.
骨髓间充质干细胞（BMSCs）是骨再生治疗、组织工程和绝经后骨质疏松症的基础。患者之间供体的变异、细胞异质性和分化能力的不可预测性降低了 BMSCs 用于再生细胞治疗的效果。细胞表面糖蛋白 CD24 在人 BMSCs 的成骨与成脂分化过程中表现出最显著的差异表达。因此，CD24 可能代表具有增强成骨潜能的 BMSC 亚群的选择性生物标志物。在未分化的人 BMSCs 中，CD24 细胞表面表达在供体之间存在差异（范围：2%-10%），并在成骨分化时增加 2-4 倍。引人注目的是，FACS 分选的 CD24 细胞表现出矿化延迟和脂肪细胞分化能力降低。对 CD24 和 CD24 BMSCs 的 RNAseq 分析确定了少数在 CD24 细胞中表达增加的基因，这些基因与细胞黏附、迁移和细胞外基质有关。下调的基因与细胞周期调控有关，生物测定显示 CD24 细胞增殖能力降低。因此，细胞表面糖蛋白 CD24 的表达鉴定了具有降低增殖能力和细胞外基质矿化能力的人 BMSC 亚群。BMSC 群体之间的功能特化可能通过支持促进骨骼组织形成、稳态和修复的细胞活动来支持其再生潜力和治疗成功。
