Background: Mesenchymal stem/stromal cells (MSCs) exert therapeutic effects largely through immunomodulatory and paracrine mechanisms. Pharmacological preconditioning strategies have been proposed to enhance MSC functionality and therapeutic efficacy. Curcumin possesses anti-inflammatory and epigenetic regulatory properties; however, the effects of curcumin nanomicelles on inflammation-associated genes, regulatory microRNAs, and
DNA methylation patterns in Wharton's jelly-derived MSCs (WJ-MSCs) remain incompletely understood. Objectives: This study investigated the molecular effects of curcumin nanomicelles on inflammatory regulatory pathways in WJ-MSCs.Methods: WJ-MSCs were isolated from human umbilical cords and characterized by flow cytometry and multilineage differentiation assays. Cell viability following exposure to curcumin nanomicelles was assessed using the MTT assay. Cells were treated with ۲۰ μM and ۷۰ μM curcumin nanomicelles for ۲۴ h. Expression levels of IκBα, TGF-β۱, miR-۲۱, and
miR-۱۴۶a were evaluated by quantitative real-time PCR. Promoter methylation status of IκBα and TGF-β۱ was analyzed using methylation-sensitive high-resolution melting (MS-HRM).Results:
Curcumin nanomicelles induced dose-dependent molecular alterations in WJ-MSCs. Treatment with ۷۰ μM significantly increased IκBα expression and reduced
miR-۲۱ expression compared with untreated controls (P < ۰.۰۵). TGF-β۱ expression was significantly increased following treatment with ۲۰ μM curcumin nanomicelles, whereas no significant change was observed at ۷۰ μM.
miR-۱۴۶a expression was significantly decreased at both tested concentrations. Despite these transcriptional and post-transcriptional changes, no significant alterations in promoter methylation patterns of either IκBα or TGF-β۱ were detected after ۲۴ h of treatment.Conclusion:
Curcumin nanomicelles modulated inflammation-associated gene expression and regulatory microRNAs in WJ-MSCs without inducing detectable promoter methylation changes in IκBα or TGF-β۱. These findings suggest that the early molecular effects of curcumin nanomicelles are predominantly mediated by transcriptional and post-transcriptional mechanisms. The observed modulation of inflammatory regulatory pathways supports further investigation of curcumin nanomicelles as a potential
MSC preconditioning strategy; however, additional protein-level, functional, and disease-model studies are required to determine their translational relevance.