Investigation of melt-spun pure Mg and MgCuCa alloys extracts on the fate of human adipose-derived mesenchymal stem cells

• Metal-spun pure Mg and MgCuCa alloys demonstrate the homogeneous microstructrure and biodegradation behaviors. • Pure Mg extracts significantly enhanced the expression of neuronal marker genes, indicating a propensity to induce neuronal lineage commitment. • MgCuCa alloy extracts, especially Cu and Ca ions, enhanced SOX9 expression, suggesting a potential role in chondrogenic differentiation. • P1 hADSCs displayed greater ionic tolerance than P3 cells, emphasizing the necessity of standardizing cell sources in therapeutic protocols. Human adipose-derived mesenchymal stem cells (hADSCs) have significant therapeutic potential for neurological disorders, but their specific differentiation remains a challenge. In this study, MgCuCa alloys and pure Mg, prepared by melt-spinning, were designed to investigate the effects of their extract liquids on the differentiation of hADSCs. The results indicated that certain concentrations of Mg and MgCuCa extracts, such as 7.73 mM Mg and 5.65 mM MgCuCa, did not exhibit significant cytotoxicity towards hADSCs. Rather, they inhibited the in vitro differentiation of hADSCs into osteoblasts, chondrocytes, and adipocytes. Importantly, these extracts upregulated the expression of neuronal marker genes, including NES, GAP43, and MAP2, suggesting a potential induction of hADSCs towards a neural lineage. RNA sequencing analysis revealed that the differentially expressed genes were predominantly enriched in signaling pathways related to stem cell differentiation, such as Notch, Wnt, TGF-β, PI3K-AKT, and MAPK. Gene set enrichment analysis (GSEA) further suggested the inhibition of these pathways. Additionally, the CuCa components of MgCuCa promoted the expression of SOX9, which may enhance the chondrogenic differentiation of hADSCs. In conclusion, Mg and MgCuCa extracts regulate the fate of hADSCs by inhibiting non-neural differentiation and promoting neural-like differentiation through modulation of key signaling pathways. This study offers new insights into the use of metal-ion-based materials for neural regeneration. Future research should focus on optimizing ion composition, concentration, and pH, as well as considering the type and source of mesenchymal stem cells, to enhance the effectiveness and specificity of hADSC-based therapies for central nervous system diseases.