α2-6 sialylation is a marker of the differentiation potential of human mesenchymal stem cells

Human somatic stem cells such as human mesenchymal stem cells (hMSCs) are considered attractive cell sources for stem cell-based therapy. However, quality control issues have been raised concerning their safety and efficacy. Here we used lectin microarray technology to identify cell surface glycans as markers of the differentiation potential of stem cells. We found that alpha 2-6 Sialic Acid (Sia)specific lectins show stronger binding to early passage adipose-derived hMSCs (with differentiation ability) than late passage cells (without the ability to differentiate). Flow cytometry analysis using alpha 2-6Sia-specific lectins supported the results obtained by lectin microarray. Similar results were obtained for bone marrow-derived hMSCs and cartilage tissue-derived chondrocytes. Little or no binding of alpha 2-6Sia-specific lectins was observed for human dermal fibroblasts, which are unable to differentiate, suggesting that the binding of alpha 2-6Sia-specific lectins is associated with the differentiation ability of cells, but not to their capacity to proliferate. Quantitative analysis of the linkage mode of Sia using anion-exchange chromatography showed that the percentage of alpha 2-6Sia linkage type was higher in early passage adipose-derived hMSCs than late passage cells. Integrin alpha 5 was found to be a carrier protein of alpha 2-6Sia. Sialidase treatment significantly reduced the differentiation efficiency of bone marrow-derived hMSCs. Based on these findings, we propose that alpha 2-6sialylation is a marker of differentiation potential in stem cells such as adipose-derived hMSCs, bone marrow-derived hMSCs, and cartilage tissue-derived chondrocytes.