糖尿病皮肤慢性创面无细胞治疗的进展与问题

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

背景:糖尿病皮肤溃疡是糖尿病的难治并发症之一,发生后迁延不愈。以往研究发现,间充质干细胞具有组织修复和炎症免疫调节能力,并且相关研究表明间充质干细胞可能主要是通过旁分泌效应分泌各种细胞因子和外泌体等,发挥组织与创面修复作用。因而可使用生长因子、间充质干细胞条件培养基及外泌体等治疗糖尿病皮肤慢性创面,以直接或间接机制对伤口愈合产生积极影响。目的:总结生长因子、条件培养基和外泌体等促进糖尿病皮肤慢性创面修复的相关机制、应用效果,以及无细胞治疗在当前研究的局限性。方法:由第一作者检索PubMed及Web of Science数据库中收录的相关文献,检索词为“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”,文献检索时限为2005年1月至2022年2月,经过阅读并筛选整理,选择与综述内容相符的文献,最终确定整理出75篇文献进行综述。结果与结论:①间充质干细胞条件培养基、外泌体和生长因子可通过不同机制改善局部微环境,促进慢性创面的愈合;②通过条件培养基、外泌体和生长因子与新兴的组织工程生物学材料(如细胞支架、水凝胶等)相结合,可使其发挥更强的促进慢性创面愈合的作用;③基于间充质干细胞条件培养基、外泌体、生长因子的无细胞疗法是促进慢性创面修复的极有前景的治疗策略,要实现由临床前研究转化到临床研究,确保其用于患者治疗的安全性,还需要进行更多的研究,以查明相应的治疗作用机制。

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.