Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat‐shock protein family

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.