Department of Anatomical Sciences, School of Medicine, Afzalipour University of Medical Sciences, Kerman, Iran.
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, 1985717443, Tehran, Iran.
Arch Dermatol Res. 2020 Jul;312(5):325-336. doi: 10.1007/s00403-019-02016-6. Epub 2019 Nov 30.
Fibroblast plays a key role in wound healing, and the advantages of mesenchymal stem cells (MSC) secretome in wound healing have previously been reported. In the present study, we investigated the impact of human bone marrow MSC-conditioned media (CM) on skin wound healing in diabetic rats and found that some improvements occurred mainly through fibroblast functions. Then, we scrutinized the impact of MSC-CM treatment on fibroblast cellular behavior by culturing human dermal fibroblasts (HDFs) in a high-glucose (HG) medium, as an in vitro diabetic model. In vivo findings revealed significant improvements in some healing kinetics of diabetic wound which received MSC-CM. Particularly, MSC-CM-treated diabetic wounds reached considerably higher percentages of wound closure. Also, the granulation tissue of these wound had less pronounced inflammatory response, better tissue remodeling, and more vascularization compared with non-treated diabetic ones. Gene expression analyses indicated that MSC-CM treatment leads to upregulation of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) genes. In addition, a significantly higher cell viability/proliferation, migration, and bFGF gene expression were observed when MSC-CM was used to treat HDFs in HG culture media. Based on these findings, it is suggested that MSC-CM could promote wound repair and skin regeneration, in some major processes, via improvement of cellular behaviors of fibroblasts in the diabetic microenvironment. The beneficial advantages of mesenchymal stem cells-conditioned media on fibroblast cellular behaviors and wound healing may lead to establish a novel approach as an alternative therapeutic procedure to cure chronic wounds in diabetic conditions.
成纤维细胞在伤口愈合中起着关键作用，间充质干细胞（MSC）分泌在伤口愈合中的优势此前已有报道。在本研究中，我们研究了人骨髓 MSC 条件培养基（CM）对糖尿病大鼠皮肤伤口愈合的影响，发现一些改善主要是通过成纤维细胞功能发生的。然后，我们通过在高糖（HG）培养基中培养人真皮成纤维细胞（HDF）来仔细研究 MSC-CM 处理对成纤维细胞细胞行为的影响，作为体外糖尿病模型。体内研究结果表明，接受 MSC-CM 治疗的糖尿病伤口的某些愈合动力学得到了显著改善。特别是，MSC-CM 治疗的糖尿病伤口达到了更高的闭合百分比。此外，与未治疗的糖尿病伤口相比，这些伤口的肉芽组织炎症反应较轻，组织重塑更好，血管化程度更高。基因表达分析表明，MSC-CM 处理可导致表皮生长因子（EGF）和碱性成纤维细胞生长因子（bFGF）基因的上调。此外，当在 HG 培养基中使用 MSC-CM 处理 HDF 时，观察到细胞活力/增殖、迁移和 bFGF 基因表达显著增加。基于这些发现，我们认为 MSC-CM 可通过改善糖尿病微环境中成纤维细胞的细胞行为来促进伤口修复和皮肤再生，在一些主要过程中发挥作用。间充质干细胞条件培养基对成纤维细胞行为和伤口愈合的有益优势可能为治疗糖尿病慢性伤口提供一种新的治疗方法。
