人脐带间充质干细胞外泌体装载miR-132-3p促进皮肤伤口愈合的潜在效果

Human umbilical cord mesenchymal stem cell-derived exosomes loaded with miR-132-3p promote skin wound healing

摘要:

慢性难愈合创面严重影响多种疾病患者的康复效果，已成为临床上亟需解决的重点问题。干细胞外泌体因其生物相容性好和生理活性高的特点，不仅具有促进皮肤伤口愈合的积极效果，也被尝试用作其他类型小分子药物的载体。miRNA具有刺激细胞增殖和再上皮化的应用潜力，但稳定性差的特点限制了其临床应用。本研究使用人脐带间充质干细胞外泌体(human umbilical cord mesenchymal stem cell-derived exosomes, UMSC-EXOs)装载miR-132-3p，分析其对人包皮成纤维细胞(human foreskin fibroblast-1, HFF-1)的作用效果。结果显示，miR-132-3p@UMSC-EXOs相比空载外泌体可以更有效地促进HFF-1的增殖和迁移,并且降低胞内活性氧水平。实时荧光定量多聚核苷酸链式反应(quantitative real-time polymerase chain reaction, qRT-PCR)和蛋白质印迹(Western blotting)检测进一步发现，miR-132-3p@UMSC-EXOs影响了多种细胞外基质重塑和炎性相关基因的转录和蛋白质表达，提示其具有上调胶原蛋白合成，提高细胞外基质代谢水平等能够促进皮肤伤口愈合的潜在效果。

Abstract:

Chronic non-healing wounds significantly impair patient rehabilitation and remain a critical clinical challenge. Stem cell-derived exosomes, owing to their biocompatibility and physiological activity, have emerged as a promising therapeutic approach in regenerative medicine. Beyond their intrinsic wound-healing properties, exosomes are increasingly explored as carriers for small-molecule drugs to enhance synergistic treatment effects. Although microRNAs (miRNAs) exhibit potential in promoting cell proliferation and re-epithelialization, their clinical application is hindered by poor stability. In this study, we investigated the therapeutic effects of miR-132-3p-loaded human umbilical mesenchymal stem cell-derived exosomes (miR-132-3p@UMSC-EXOs) on human foreskin fibroblast-1 (HFF-1). Our findings demonstrated that miR-132-3p@UMSC-EXOs significantly enhanced proliferation and migration of HFF-1, while reducing intracellular reactive oxygen species (ROS) levels compared with unloaded exosomes. Furthermore, qRT-PCR and Western blotting analyses revealed that miR-132-3p@UMSC-EXOs modulated the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation, suggesting their potential to upregulate collagen synthesis and improve ECM metabolism. These results highlight the therapeutic promise of miR-132-3p@UMSC-EXOs in accelerating wound healing.