这项临床前概念验证研究旨在评估分泌体治疗在患有压疮的糖尿病小鼠中的有效性。我们使用了定制的基于透明质酸(HA)的多孔海绵,用正常培养基或源自人间充质基质细胞(MSC)的分泌组再水化,以达到水凝胶的一致性。应用于皮肤溃疡后,与媒介物组相比,单水凝胶和水凝胶+分泌组组合均加速伤口闭合.值得注意的是,分泌体的存在显着增强了水凝胶的愈合效果,与媒介物组相比,表皮较厚,愈合区域的血运重建增加。值得注意的是,愈合皮肤的分子分析显示,在水凝胶+分泌组组合治疗的溃疡中,参与延迟伤口愈合和异常炎症反应的基因显著下调,与仅使用水凝胶处理的那些相比。此外,在比较使用胎儿真皮MSCs和脐带MSCs的分泌组时,我们发现治疗结果无显著差异.这一观察结果得到了两个分泌体的蛋白质组学图谱的支持,这表明一个共同的分子特征负责观察到的治疗效果。
This preclinical proof-of-concept study aimed to evaluate the effectiveness of secretome therapy in diabetic mice with pressure ulcers. We utilized a custom-made hyaluronic acid (HA)-based porous sponge, which was rehydrated either with normal culture medium or secretome derived from human mesenchymal stromal cells (MSCs) to achieve a hydrogel consistency. Following application onto skin ulcers, both the hydrogel-only and the hydrogel + secretome combination accelerated wound closure compared to the vehicle group. Notably, the presence of secretome significantly enhanced the healing effect of the hydrogel, as evidenced by a thicker epidermis and increased revascularization of the healed area compared to the vehicle group. Notably, molecular analysis of healed skin revealed significant downregulation of genes involved in delayed wound healing and abnormal inflammatory response in ulcers treated with the hydrogel + secretome combination, compared to those treated with the hydrogel only. Additionally, we found no significant differences in therapeutic outcomes when comparing the use of secretome from fetal dermal MSCs to that from umbilical cord MSCs. This observation is supported by the proteomic profile of the two secretomes, which suggests a shared molecular signature responsible of the observed therapeutic effects.