Palumbo Fabio Salvatore, Calligaris Matteo, Calzà Laura, Fiorica Calogero, Baldassarro Vito Antonio, Carreca Anna Paola, Lorenzini Luca, Giuliani Alessandro, Carcione Claudia, Cuscino Nicola, Pitarresi Giovanna, Scilabra Simone Dario, Conaldi Pier Giulio, Chinnici Cinzia Maria
Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, via Archirafi 32, 90123, Palermo, Italy.
Proteomic Group, Ri.MED Foundation c/o IRCCS ISMETT, via E. Tricomi 5, 90127, Palermo, Italy.
Regen Ther. 2024 Jul 27;26:520-532. doi: 10.1016/j.reth.2024.07.008. eCollection 2024 Jun.
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.
这项临床前概念验证研究旨在评估分泌组疗法对患有压疮的糖尿病小鼠的有效性。我们使用了一种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）的分泌组对其进行再水化以达到水凝胶的稠度。在将其应用于皮肤溃疡后，与载体组相比，仅水凝胶组和水凝胶+分泌组组合均加速了伤口愈合。值得注意的是，分泌组的存在显著增强了水凝胶的愈合效果，与载体组相比，愈合区域的表皮更厚且血管再生增加证明了这一点。值得注意的是，与仅用水凝胶治疗的溃疡相比，对愈合皮肤的分子分析显示，在用凝胶+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。此外，我们发现，比较胎儿真皮间充质干细胞分泌组与脐带间充质干细胞分泌组的使用情况时，治疗结果没有显著差异。这一观察结果得到了两种分泌组蛋白质组学图谱的支持，该图谱表明存在共同的分子特征导致了观察到的治疗效果。
