2022, Vol. 26 ›› Issue (31): 5076-5084

Mechanism and application prospects of mesenchymal stem cell exosomes gene-modified microRNA in the treatment of diabetic foot

Deng Xiaohui1, Zhang Zengzeng2, Zhang Zhihua3, Zhu Lingyan1   

Abstract: BACKGROUND: Diabetic foot is one of the most serious complications of diabetes. The treatment of foot complications is a major problem that needs to be solved urgently in the medical care of diabetic people. Recent studies have shown that mesenchymal stem cell exosomes genetically modified miRNA has a great potential for promoting diabetic foot’s angiogenesis and tissue repair.  
OBJECTIVE: To summarize the research progress of mesenchymal stem cell exosomes gene-modified miRNA in the treatment of diabetic foot, focus on the role of exosomal gene-modified miRNA in the treatment of diabetic foot, and systematically explain the molecular mechanism of how mesenchymal stem cell exosomes gene-modified miRNA promotes angiogenesis and tissue repair in the inflammatory microenvironment so as to lay a solid theoretical foundation for the advancement of later clinical trials.
METHODS: PubMed, Web of Science, and Wiley electronic journal databases were searched to retrieve related articles with “mesenchymal stem cells; exosomes; gene modification; diabetic foot; miRNA; inflammation; insulin resistance; angiogenesis; wound healing; tissue engineering; tissue reparation” as the English search terms. Finally, 89 English documents were included for summary.  
RESULTS AND CONCLUSION: (1) Mesenchymal stem cell exosomes gene-modified miRNA has a significant effect on diabetic foot tissue regeneration and wound healing. Its main mechanisms include promoting angiogenesis by participating in transcriptional regulation of gene expression, accelerating wound re-epithelialization, inhibiting apoptosis and inflammation, regulating cell regeneration, and protecting β cells and regulating insulin resistance, thereby playing an important role in healing diabetic foot wounds. (2) Mesenchymal stem cell exosomes gene-modified miRNA can repair pancreatic tissue, improve obesity and insulin resistance, and delay the progression of diabetes and its complications by inhibiting β-cell apoptosis and increasing the sensitivity of insulin target tissues. (3) Targeted editing of the genome through regular clusters of interval short palindrome repeats and Cas9 (CRISPR-Cas9) technology can achieve precise gene modification, change the biological characteristics of miRNAs, and regulate the gene network to change its transcription and translation in target cells and target tissues to achieve the therapeutic effect. (4) This article comprehensively summarizes how exosomes miRNA is regulated by different gene loci to achieve the healing effect on refractory wounds of diabetic foot. (5) Exosomes miRNA also shows a great potential as a biomarker for diabetic foot treatment targets, early diagnosis, efficacy evaluation and prognostic diagnosis. (6) Seeking the best mesenchymal stem cell exosomes gene-modified miRNA therapy is expected to become a new technology for diabetic foot treatment.
Key words: mesenchymal stem cells, exosomes, gene modification, miRNA, diabetic foot, inflammation, insulin resistance, angiogenesis, wound healing, tissue engineering