2023, Vol. 27 ›› Issue (6): 962-969

Advances and problems in cell-free treatment of diabetic skin chronic wounds

Xu Qijing1, Yang Yichun2, Lei Wei2, Yang Ying2, Yu Jiang3, Xia Tingting2, Zhang Meng3, Zhang Tao2, 3, Zhang Qian1   

Abstract: BACKGROUND: Diabetic skin ulcer is one of the refractory complications of diabetes mellitus and cannot be cured after occurrence. Previous studies have found that mesenchymal stem cells have the ability of tissue repair and inflammatory immune regulation. Relevant studies have shown that mesenchymal stem cells may secrete various cytokines and exosomes mainly through the paracrine effect and play a role in tissue and wound repair, and. Therefore, the use of growth factors, mesenchymal stem cell conditioned mediums and exosomes in the treatment of chronic diabetic skin wounds can have a positive effect on wound healing through direct or indirect mechanisms.  
OBJECTIVE: To summarize the related mechanisms and application effects of growth factors, conditioned mediums and exosomes on promoting diabetic skin chronic wound repair, as well as the limitations of cell-free therapy in current research.
METHODS: The first author searched relevant articles published from January 2005 to February 2022 on PubMed and Web of Science. The key words were “diabetes, diabetic foot, diabetic foot ulcers, chronic wound, mesenchymal stem cells, cell-free, exosomes, growth factors, conditioned mediums, wound healing, tissue repair, angiogenesis, regeneration, biomaterial ” in English. After reading, screening and sorting, the articles consistent with the content of the review were collected. Finally, 75 articles were selected for review.  
RESULTS AND CONCLUSION: (1) Mesenchymal stem cell conditioned mediums, exosomes and growth factors can improve the local microenvironment and promote the healing of chronic wounds through different mechanisms. (2) The combination of conditioned mediums, exosomes and growth factors with emerging tissue engineering biological materials (such as cell scaffolds and hydrogels) can make them play a stronger role in promoting chronic wound healing. (3) Cell-free therapy with conditioned medium of mesenchymal stem cells, exosomes and growth factors is a promising therapeutic strategy for promoting chronic wound healing. More research is needed to identify the mechanism of action in order to transfer from preclinical studies to clinical studies and ensure its safety in patients.
Key words: diabetic foot ulcer, chronic wound, mesenchymal stem cell, cell-free therapy, exosome, growth factor, conditional medium, biological material, review