Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.

中文翻译：

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富含 IL-10 modRNA 的人脂肪来源的多能基质细胞可改善糖尿病伤口愈合：触发巨噬细胞表型转变


糖尿病伤口由于愈合受损而对再生医学提出了重大挑战，其特点是长期炎症和组织修复缺陷，这主要是由促炎巨噬细胞表型倾斜引起的。本研究探讨了富含白细胞介素 10 (IL-10) 化学修饰 mRNA (modRNA) 的人脂肪源性多能基质细胞 (hADSC) 在完善的糖尿病伤口小鼠模型中的治疗潜力。本研究中使用的 modRNA 使用 N1-甲基假尿苷-5'-三磷酸 (m1Ψ) 进行化学修饰，并替换为尿苷-5-三磷酸。体外实验表明，IL-10 modRNA 转染的 hADSC 有效调节巨噬细胞极化，使其具有抗炎表型。使用完善的小鼠模型进行的体内实验表明，hADSC 移植模型IL-10术后第 5 天 (POD5) 显着改善伤口愈合结果，包括加速伤口闭合、增强上皮再形成、促进 M2 极化、改善胶原蛋白沉积和增加新血管形成。本研究得出的结论是，富含 IL-10 modRNA 的 hADSC 为糖尿病伤口愈合提供了一种有前途的治疗方法，IL-10 的给药时机对其有效性起着至关重要的作用。这些细胞调节巨噬细胞极化并促进组织修复，显示出它们改善糖尿病伤口管理的潜力。