Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Am J Physiol Cell Physiol. 2023 Jun 1;324(6):C1307-C1319. doi: 10.1152/ajpcell.00541.2022. Epub 2023 May 8.
It is a widespread and difficult problem that refractory diabetic wounds have a poor local environment and prolonged inflammatory irritation. Tumor cell-derived exosomes play an important role in the development of tumors, as they can promote tumor cell proliferation, migration, and invasion and enhance tumor cell activity. However, tumor tissue-derived exosomes (Ti-Exos) have been less studied, and it is unclear how they affect wound healing. In this study, we extracted Ti-Exos from human oral squamous carcinoma and paracancerous tissue by ultracentrifugation, size exclusion chromatography, and ultrafiltration and performed exosome characterization. In vitro, the oral squamous cell carcinoma tissue-derived exosomes (OSCC Ti-Exos) promoted the proliferation and migration of endothelial cells, keratinocytes, and fibroblasts. In addition, in vivo experiments showed that the OSCC Ti-Exos accelerated the healing of diabetic wounds and were safe in mice. In contrast, there was no promoting effect of paracancerous tissue-derived exosomes either in vivo or in vitro. In conclusion, OSCC Ti-Exos promoted the healing of diabetic wounds, demonstrated preliminary biosafety in mice, and have promise as therapeutic applications. Diabetic wound healing has become a public health issue that lacks effective treatment. We collected oral squamous cell carcinoma samples and paracancerous tissue and extracted Ti-Exos for verification. In vitro assays revealed that OSCC Ti-EVs could enhance the proliferation and migration of endothelial cells, keratinocytes, and fibroblasts in diabetic cell model. In vivo assays also verified that OSCC Ti-Exos could promote diabetic wound healing, demonstrated preliminary biosafety in mice, and have promise as therapeutic applications.
难治性糖尿病创面局部环境差,炎症刺激时间长,这是一个普遍且棘手的问题。肿瘤细胞衍生的外泌体在肿瘤的发展中起着重要作用,因为它们可以促进肿瘤细胞的增殖、迁移和侵袭,并增强肿瘤细胞的活性。然而,肿瘤组织衍生的外泌体(Ti-Exos)研究较少,其如何影响伤口愈合尚不清楚。在这项研究中,我们通过超速离心、分子筛层析和超滤从人口腔鳞状细胞癌和癌旁组织中提取 Ti-Exos,并进行外泌体表征。在体外,口腔鳞状细胞癌组织衍生的外泌体(OSCC Ti-Exos)促进了内皮细胞、角质形成细胞和成纤维细胞的增殖和迁移。此外,体内实验表明,OSCC Ti-Exos 加速了糖尿病创面的愈合,在小鼠中是安全的。相比之下,癌旁组织衍生的外泌体在体内和体外均无促进作用。总之,OSCC Ti-Exos 促进了糖尿病创面的愈合,在小鼠中表现出初步的生物安全性,有望作为治疗应用。糖尿病创面愈合已成为一个缺乏有效治疗方法的公共健康问题。我们收集了口腔鳞状细胞癌样本和癌旁组织,并提取了 Ti-Exos 进行验证。体外实验表明,OSCC Ti-EVs 可以增强糖尿病细胞模型中内皮细胞、角质形成细胞和成纤维细胞的增殖和迁移。体内实验也验证了 OSCC Ti-Exos 可以促进糖尿病创面愈合,在小鼠中表现出初步的生物安全性,有望作为治疗应用。