Trehalose enhances neuronal differentiation with VEGF secretion in human iPSC-derived neural stem/progenitor cells.

Introduction: Cell transplantation therapy has emerged as a promising approach in regenerative medicine for treating neurological diseases. Neural stem/progenitor cell (NS/PC) transplantation has demonstrated therapeutic efficacy; however, its potential remains limited by suboptimal differentiation and insufficient secretion of pro-healing growth factors. Trehalose, a glucose disaccharide, has been shown to exert neuroprotective effects by inducing autophagy and stabilizing cellular structures. Recent studies suggest that trehalose can modulate growth factor secretion through the CDKN1A/p21 pathway. However, its impact on human induced pluripotent stem cell-derived NS/PCs (hiPSC-NS/PCs) remains unclear. This study investigates the effect of trehalose on neuronal differentiation, cell viability, and growth factor expression in hiPSC-NS/PCs to explore its potential in enhancing transplantation therapy. Methods: hiPSC-NS/PCs were cultured as neurospheres and treated with trehalose (10 mg/ml or 40 mg/ml) for 7 days. Cell viability was assessed using CellTiter Glo® assay. Gene expression analysis was conducted via qRT-PCR and RNA-seq, particularly focusing on Results: Treatment with 10 mg/ml trehalose upregulated Conclusion: Trehalose enhances neuronal differentiation and