Beyond labeling: differential Ac₄ManNAz dosing as a tool for functional manipulation of mesenchymal stem cells

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Bioorthogonal chemistry technology serves as a powerful tool for mesenchymal stem cell (MSC) transplantation by utilizing metabolic engineering for direct cell modification either in vivo or in vitro . However, the unclear effects of varying concentrations of non-natural metabolic monosaccharides on labeling efficiency, functional impact and safety pose significant challenges for clinical translation. Herein, we screened the concentration-dependent effects of the metabolic labeling agent Ac 4 ManNAz (10-100 µM) on the functionality of MSC. Visualizing azido groups on the cell surface through bioorthogonal reactions confirmed that labeling efficiency positively correlated with the concentration of Ac 4 ManNAz. Interestingly, treatment of MSC with 50-µM Ac 4 ManNAz enhances their immune regulatory function. Mechanistically, 50-µM Ac 4 ManNAz remodels the extracellular matrix of MSC by downregulating decorin (DCN) expression to alleviate TGF- β inhibition, simultaneously upregulating serglycin (SRGN) expression to activate and stabilize TGF- β . This dual action results in increased secretion of TGF- β , thereby augmenting the immune regulatory capacity of MSC. Nevertheless, at the level of cellular motility, treatment with 50-µM Ac 4 ManNAz significantly impairs the migratory capacity of MSC. Overall, this study clearly defined the concentration effect of non-natural monosacchari

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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