Zhou Haoyu, Zhang Zhen, Liu Zhan, Sa Guodong, Jiang Mingjing, Zou Zhongyang, Shi Yingliang, Zheng Liwu, Yang Xuewen, Sa Guoliang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Orthodontic Department Division II, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
J Extracell Vesicles. 2025 Jun;14(6):e70112. doi: 10.1002/jev2.70112.
Migrasomes are newly discovered organelles with demonstrated functions in organ morphogenesis and angiogenesis. However, the effect of migrasomes in tissue repair remains unreported. Our super-resolution confocal microscopy and focused ion beam scanning electron microscopy results confirmed that migrasomes were directly connected with retraction fibres and could release their contents into the surroundings in human and rat skins and oral mucosae. Multiplex immunofluorescence staining results revealed that these retraction fibres and migrasomes originated from fibroblasts. Live-cell imaging demonstrated that human oral mucosal fibroblast-derived migrasomes could be taken up by both fibroblasts and HaCaT cells. In addition, the injection of purified fibroblast-derived migrasomes into the edges of rat skin wounds significantly accelerated wound healing. Single-cell sequencing results suggested that the clusters of keratinocytes, fibroblasts, and endothelial cells play key roles in the wound-healing process. Moreover, the expression of Vegfa, Il-6, and Col1a1 in the fibroblast subcluster was significantly upregulated. Furthermore, these purified migrasomes increased the protein levels of VEGFA, IL-6, and COL1A1 in cultured fibroblasts in vitro. Mechanistically, migrasomes may facilitate wound healing by delivering CXCL12. Thus, our research revealed that fibroblast-derived migrasomes are potential therapeutic vesicles for skin wound-healing repair.
迁移小体是新发现的细胞器，已证明其在器官形态发生和血管生成中发挥作用。然而，迁移小体在组织修复中的作用尚未见报道。我们的超分辨率共聚焦显微镜和聚焦离子束扫描电子显微镜结果证实，在人和大鼠的皮肤及口腔黏膜中，迁移小体与收缩纤维直接相连，并能将其内容物释放到周围环境中。多重免疫荧光染色结果显示，这些收缩纤维和迁移小体起源于成纤维细胞。活细胞成像表明，人口腔黏膜成纤维细胞来源的迁移小体可被成纤维细胞和HaCaT细胞摄取。此外，将纯化的成纤维细胞来源的迁移小体注射到大鼠皮肤伤口边缘可显著加速伤口愈合。单细胞测序结果表明，角质形成细胞、成纤维细胞和内皮细胞簇在伤口愈合过程中起关键作用。此外，成纤维细胞亚群中Vegfa、Il-6和Col1a1的表达显著上调。此外，这些纯化的迁移小体在体外增加了培养的成纤维细胞中VEGFA、IL-6和COL1A1的蛋白水平。从机制上讲，迁移小体可能通过递送CXCL12促进伤口愈合。因此，我们的研究表明，成纤维细胞来源的迁移小体是皮肤伤口愈合修复的潜在治疗性囊泡。
