Extracellular vesicle-enclosed miR-486-5p mediates wound healing with adipose-derived stem cells by promoting angiogenesis.
Extracellular vesicle-enclosed miR-486-5p mediates wound healing with adipose-derived stem cells by promoting angiogenesis.
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DOI：
10.1111/jcmm.15387
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Zeng Y
中科院分区：
文献类型：
--
作者：
Lu Y;Wen H;Huang J;Liao P;Liao H;Tu J;Zeng Y
脂肪来源的干细胞(ASC)被认为在伤口愈合中起着关键作用。具体地说，ASC分泌的胞外囊泡(EV)携带各种货物，如microRNAs(MiRNAs)，参与基于ASC的治疗。考虑到ASC-EVS的作用，本研究旨在探讨ASC-EVS在皮肤创面愈合中的作用，同时对其在创面愈合中的作用进行研究。在小鼠背部造成两个全层切除皮肤创面，在指定的时间点记录创面愈合情况，然后进行组织学分析和CD31、α-SMA的免疫荧光染色。将人皮肤成纤维细胞(HSFs)和人微血管内皮细胞(HMECs)分别与ASC分离的血管内皮细胞(ASC-EVS)共培养，用CCK-8、划痕试验和跨孔迁移实验评价其活性和迁移能力。以Matrigel为基础的血管生成实验检测体外培养的人脐静脉内皮细胞血管样管的形成。在小鼠模型中，ASC-EVS加速了全层皮肤伤口的愈合，增加了再上皮化，减少了瘢痕厚度，同时促进了胶原合成和血管生成。而miR-486-5P拮抗剂可阻断ASC-EVS的作用。有趣的是，miR-486-5p被发现高度富含ASC-EVS，表现出增加HSFs和HMECs的存活率和迁移率，并增强HMECs的血管生成活性。值得注意的是，我们还证明了分泌ASC-EVS的miR-486-5p通过其靶基因SP5实现了上述作用。因此，我们的结果表明，ASC-EVS释放的miR-486-5p可能是发展基于ASC的伤口愈合治疗策略的关键介质。
Adipose‐derived stem cells (ASC) are said to have a pivotal role in wound healing. Specifically, ASC‐secreted extracellular vesicles (EV) carry diverse cargos such as microRNAs (miRNAs) to participate in the ASC‐based therapies. Considering its effects, we aimed to investigate the role of ASC‐EVs in the cutaneous wound healing accompanied with the study on the specific cargo‐medicated effects on wound healing. Two full‐thickness excisional skin wounds were created on mouse dorsum, and wound healing was recorded at the indicated time points followed by histological analysis and immunofluorescence staining for CD31 and α‐SMA. Human skin fibroblasts (HSFs) and human microvascular endothelial cells (HMECs) were co‐cultured with EVs isolated from ASC (ASC‐EVs), respectively, followed by the evaluation of their viability and mobility using CCK‐8, scratch test and transwell migration assays. Matrigel‐based angiogenesis assays were performed to evaluate vessel‐like tube formation by HMECs in vitro. ASC‐EVs accelerated the healing of full‐thickness skin wounds, increased re‐epithelialization and reduced scar thickness whilst enhanced collagen synthesis and angiogenesis in murine models. However, miR‐486‐5p antagomir abrogated the ASC‐EVs‐induced effects. Intriguingly, miR‐486‐5p was found to be highly enriched in ASC‐EVs, exhibiting an increase in viability and mobility of HSFs and HMECs and enhanced the angiogenic activities of HMECs. Notably, we also demonstrated that ASC‐EVs‐secreted miR‐486‐5p achieved the aforesaid effects through its target gene Sp5. Hence, our results suggest that miR‐486‐5p released by ASC‐EVs could be a critical mediator to develop an ASC‐based therapeutic strategy for wound healing.
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影响因子：
6
作者：
Chen, Chih-Hung;Hsu, Shu-Yuan;Leu, Steve
通讯作者：
Leu, Steve
源自人内皮祖细胞的外泌体通过 Erk1/2 信号传导促进血管生成，加速皮肤伤口愈合
影响因子：
9.2
作者：
Zhang J;Chen C;Hu B;Niu X;Liu X;Zhang G;Zhang C;Li Q;Wang Y
通讯作者：
Wang Y
DOI：
10.1016/j.jid.2018.03.1498
发表时间：
2018-09
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Hellmann J;Sansbury BE;Wong B;Li X;Singh M;Nuutila K;Chiang N;Eriksson E;Serhan CN;Spite M
通讯作者：
Spite M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.6
作者：
Mou, Shan;Zhou, Muran;Wang, Zhenxing
通讯作者：
Wang, Zhenxing