Exosomes from MicroRNA-125b-Modified Adipose-Derived Stem Cells Promote Wound Healing of Diabetic Foot Ulcers.

Enqi Guo, Liang Wang, Jianlong Wu, Qiang Chen
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Abstract

INTRODUCTION Exosomes derived from Adipose-Derived Stem Cells (ADSCs-Exo) have been implicated in the enhancement of wound repair in Diabetic Foot Ulcers (DFU). OBJECTIVE The current research was designed to explore the therapeutic potential and underlying mechanisms of ADSCs-Exo modified with microRNA-125b (miR-125b) in the context of DFU. METHODS Rat models with DFU and human umbilical vein endothelial cells (HUVECs) subjected to high glucose (HG) conditions served as experimental systems and were administered miR-125b-engineered ADSCs-Exo. Then, the expressions of CD34, Ki-67, angiogenesis-related factors (VEGF and TGFβ-1), angiogenesis inhibitor DLL-4, and inflammation-related proteins (TLR-4 and IL-6) were detected. RESULTS MiR-125b was upregulated in ADSCs-Exo. MiR-125b-mimics transfection in ADSCs- Exo reduced inflammatory infiltration and promoted granulation formation and wound healing in wound tissues. MiR-125b-mimics-modified ADSCs-Exo injection increased the expression of CD34, Ki-67, VEGF, and TGFβ-1, whereas decreased the expression of DLL-4, TLR-4, and IL-6 in wound tissues of DFU rats. In addition, miR-125b-mimics-ADSCs-Exo injection reversed the negative effects of HG on the proliferation, migration, and angiogenesis of HUVECs, as well as the positive effects of cell apoptosis. Moreover, miR-125b-inhibitor-ADSCs-Exo injection had the opposite effects to miR-125b-mimics-ADSCs-Exo. CONCLUSION ADSCs-Exo promoted wound healing of DFU rats, especially when overexpressing miR-125b.
MicroRNA-125b修饰的脂肪来源干细胞外泌体促进糖尿病足溃疡的伤口愈合
目的目前的研究旨在探索经microRNA-125b(miR-125b)修饰的ADSCs-Exo在糖尿病足溃疡(DFU)中的治疗潜力和潜在机制。方法以DFU大鼠模型和高糖(HG)条件下的人脐静脉内皮细胞(HUVECs)为实验系统,给它们注射经miR-125b修饰的ADSCs-Exo。结果miR-125b在ADSCs-Exo中上调。在 ADSCs- Exo 中转染 MiR-125b 模拟物可减少炎症浸润,促进肉芽形成和伤口组织的愈合。经 MiR-125b 改性的 ADSCs-Exo 注射液增加了 DFU 大鼠伤口组织中 CD34、Ki-67、VEGF 和 TGFβ-1 的表达,同时降低了 DLL-4、TLR-4 和 IL-6 的表达。此外,miR-125b-mimics-ADSCs-Exo注射液还逆转了HG对HUVECs增殖、迁移和血管生成的负面影响,以及对细胞凋亡的正面影响。此外,miR-125b抑制剂-ADSCs-Exo注射液与miR-125b模拟物-ADSCs-Exo注射液的作用相反。
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