Wang Yixi, Cheng Lihui, Zhao Hanxing, Li Zhengyong, Chen Junjie, Cen Ying, Zhang Zhenyu
Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.
Department of Central Sterile Supply, West China Hospital, Sichuan University, Chengdu, China.
Front Med (Lausanne). 2022 Jun 9;9:858824. doi: 10.3389/fmed.2022.858824. eCollection 2022.
Large skin defects caused by burns, unhealing chronic wounds, and trauma, are still an intractable problem for clinicians and researchers. Ideal skin regeneration includes several intricate and dynamic stages of wound repair and regeneration of skin physiological function. Adipose-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs) with abundant resources and micro-invasive extraction protocols, have been reported to participate in each stage of promoting skin regeneration via paracrine effects. As essential products secreted by ADSCs, extracellular vesicles (EVs) derived from ADSCs (ADSC-EVs) inherit such therapeutic potential. However, ADSC-EVs showed much more clinical superiorities than parental cells. ADSC-EVs carry various mRNAs, non-coding RNAs, proteins, and lipids to regulate the activities of recipient cells and eventually accelerate skin regeneration. The beneficial role of ADSCs in wound repair has been widely accepted, while a deep comprehension of the mechanisms of ADSC-EVs in skin regeneration remains unclear. In this review, we provided a basic profile of ADSC-EVs. Moreover, we summarized the latest mechanisms of ADSC-EVs on skin regeneration from the aspects of inflammation, angiogenesis, cell proliferation, extracellular matrix (ECM) remodeling, autophagy, and oxidative stress. Hair follicle regeneration and skin barrier repair stimulated by ADSC-EVs were also reviewed. The challenges and prospects of ADSC-EVs-based therapies were discussed at the end of this review.
烧伤、慢性难愈伤口和创伤导致的大面积皮肤缺损，仍然是临床医生和研究人员面临的棘手问题。理想的皮肤再生包括伤口修复和皮肤生理功能再生的几个复杂且动态的阶段。脂肪来源干细胞（ADSCs）是一种间充质干细胞（MSCs），资源丰富且提取方式微创，据报道其可通过旁分泌作用参与促进皮肤再生的各个阶段。作为ADSCs分泌的重要产物，源自ADSCs的细胞外囊泡（ADSC-EVs）继承了这种治疗潜力。然而，ADSC-EVs显示出比亲代细胞更多的临床优势。ADSC-EVs携带各种mRNA、非编码RNA、蛋白质和脂质，以调节受体细胞的活性，最终加速皮肤再生。ADSCs在伤口修复中的有益作用已被广泛认可，而对ADSC-EVs在皮肤再生中的机制的深入理解仍不清楚。在本综述中，我们提供了ADSC-EVs的基本概况。此外，我们从炎症、血管生成、细胞增殖、细胞外基质（ECM）重塑、自噬和氧化应激等方面总结了ADSC-EVs促进皮肤再生的最新机制。我们还综述了ADSC-EVs刺激毛囊再生和皮肤屏障修复的相关内容。本综述末尾讨论了基于ADSC-EVs疗法的挑战与前景。
