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Abstract：
BACKGROUND: Adipose-derived stem cells (ADSCs) hold promising application prospects in the treatment of diabetic wounds, although the underlying mechanisms of repair have not been fully elucidated. This research aimed to elucidate the mechanisms by which ADSCs promote wound healing.
METHODS: Exosomes from ADSCs were isolated and circRps5 level was identified. To investigate the role of circRps5 in the regulation, exosomes from differently treated ADSCs were used. Different exosomes were injected into the edge of the wound in diabetic mice, and the effects on wound healing status, pathology, collagen, cytokines, and macrophage phenotype were assessed. Raw264.7 cells were co-treated with high glucose and exosomes, and then cell phenotype and autophagy were examined in vitro, followed by the evaluation of miR-124-3p\'s impact on cell phenotype.
RESULTS: Exosomes from ADSCs were isolated and identified using nanoparticle tracking analysis and exosome markers. Overexpression of circRps5 accelerated wound healing, reduced inflammatory response, enhanced collagen production, and promoted the M2 transformation of macrophages. In high glucose-induced macrophages, its overexpression also inhibited excessive autophagy. When macrophages overexpressed miR-124-3p, the induction of the M2 phenotype was suppressed. Luciferase reporter assay proved the combination of circRps5 and miR-124-3p.
CONCLUSIONS: This study identifies that circRps5 carried by ADSC-Exos promotes macrophage M2 polarization through miR-124-3p. These findings provide valuable insights into the mechanism of ADSC-Exos for treating refractory diabetic wounds, laying a solid theoretical groundwork for future clinical development.
METHODS: Exosomes from ADSCs were isolated and circRps5 level was identified. To investigate the role of circRps5 in the regulation, exosomes from differently treated ADSCs were used. Different exosomes were injected into the edge of the wound in diabetic mice, and the effects on wound healing status, pathology, collagen, cytokines, and macrophage phenotype were assessed. Raw264.7 cells were co-treated with high glucose and exosomes, and then cell phenotype and autophagy were examined in vitro, followed by the evaluation of miR-124-3p\'s impact on cell phenotype.
RESULTS: Exosomes from ADSCs were isolated and identified using nanoparticle tracking analysis and exosome markers. Overexpression of circRps5 accelerated wound healing, reduced inflammatory response, enhanced collagen production, and promoted the M2 transformation of macrophages. In high glucose-induced macrophages, its overexpression also inhibited excessive autophagy. When macrophages overexpressed miR-124-3p, the induction of the M2 phenotype was suppressed. Luciferase reporter assay proved the combination of circRps5 and miR-124-3p.
CONCLUSIONS: This study identifies that circRps5 carried by ADSC-Exos promotes macrophage M2 polarization through miR-124-3p. These findings provide valuable insights into the mechanism of ADSC-Exos for treating refractory diabetic wounds, laying a solid theoretical groundwork for future clinical development.
摘要：
背景：脂肪来源的干细胞（ADSCs）在糖尿病伤口的治疗中具有广阔的应用前景。尽管潜在的修复机制尚未完全阐明。本研究旨在阐明ADSCs促进伤口愈合的机制。
方法：分离来自ADSC的外泌体并鉴定circRps5水平。为了研究circRps5在调节中的作用，使用来自不同处理的ADSC的外泌体.将不同的外泌体注射到糖尿病小鼠的伤口边缘，以及对伤口愈合状态的影响，病理学,胶原蛋白，细胞因子,和巨噬细胞表型进行评估。Raw264.7细胞与高葡萄糖和外泌体共同处理，然后在体外检查细胞表型和自噬，随后评估miR-124-3p对细胞表型的影响。
结果:使用纳米颗粒追踪分析和外泌体标记分离和鉴定来自ADSC的外泌体。circRps5过表达加速伤口愈合，炎症反应减少，增强胶原蛋白的产生，并促进巨噬细胞的M2转化。在高糖诱导的巨噬细胞中，其过度表达也抑制了过度的自噬。当巨噬细胞过表达miR-124-3p时，M2表型的诱导被抑制。荧光素酶报告基因测定证明了circRps5和miR-124-3p的组合。
结论：本研究确定ADSC-Exos携带的circRps5通过miR-124-3p促进巨噬细胞M2极化。这些发现为ADSC-Exos治疗难治性糖尿病伤口的机制提供了有价值的见解，为今后临床发展奠定坚实的理论基础。
方法：分离来自ADSC的外泌体并鉴定circRps5水平。为了研究circRps5在调节中的作用，使用来自不同处理的ADSC的外泌体.将不同的外泌体注射到糖尿病小鼠的伤口边缘，以及对伤口愈合状态的影响，病理学,胶原蛋白，细胞因子,和巨噬细胞表型进行评估。Raw264.7细胞与高葡萄糖和外泌体共同处理，然后在体外检查细胞表型和自噬，随后评估miR-124-3p对细胞表型的影响。
结果:使用纳米颗粒追踪分析和外泌体标记分离和鉴定来自ADSC的外泌体。circRps5过表达加速伤口愈合，炎症反应减少，增强胶原蛋白的产生，并促进巨噬细胞的M2转化。在高糖诱导的巨噬细胞中，其过度表达也抑制了过度的自噬。当巨噬细胞过表达miR-124-3p时，M2表型的诱导被抑制。荧光素酶报告基因测定证明了circRps5和miR-124-3p的组合。
结论：本研究确定ADSC-Exos携带的circRps5通过miR-124-3p促进巨噬细胞M2极化。这些发现为ADSC-Exos治疗难治性糖尿病伤口的机制提供了有价值的见解，为今后临床发展奠定坚实的理论基础。
