The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

中文翻译：

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人胎儿间充质干细胞分泌组通过热休克蛋白家族促进无疤痕糖尿病伤口愈合


糖尿病足溃疡患者的高死亡率促使有效的生物医学药物的出现。衰老是衰老引起的糖尿病伤口衰退的主要原因之一。我们之前的研究已经证明了源自人胎儿间充质干细胞（hfMSC）的分泌蛋白组的抗衰老作用。本研究旨在探索 hfMSC 分泌组 (HFS) 通过抗衰老在伤口愈合中的潜在作用。同时，我们努力克服干细胞分泌组学临床应用中的一些障碍。采用垂直生物反应器和微载体来扩增 hfMSC 并大规模生产 HFS。然后对 HFS 进行冻干 (L-HFS)。在链脲佐菌素 (STZ) 诱导的糖尿病大鼠模型中，PLGA（聚乳酸-乙醇酸共聚物）颗粒用于封装并保护 L-HFS 免遭降解。结果表明，HFS-PLGA 通过促进血管形成和抑制皮肤伤口床炎症来显着促进伤口愈合。我们进一步分析了HFS的内容。使用用于相对和绝对定量的同量异位标签 (ITRAQ) 和无标记方法来鉴定分泌蛋白组中的肽。生物信息学分析表明，外泌体生产相关的单一途径和热休克蛋白家族可作为干细胞分泌蛋白组生产的生物功能标记和质量控制。