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口腔鳞状细胞癌组织来源的外泌体加速糖尿病创面愈合。

Exosomes derived from oral squamous cell carcinoma tissue accelerate diabetic wound healing.

机构信息

Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

Am J Physiol Cell Physiol. 2023 Jun 1;324(6):C1307-C1319. doi: 10.1152/ajpcell.00541.2022. Epub 2023 May 8.

DOI:10.1152/ajpcell.00541.2022
PMID:37154491
Abstract

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.

摘要

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。

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引用本文的文献

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Exosomes in Diabetic Wound Healing: Mechanisms, Applications, and Perspectives.糖尿病伤口愈合中的外泌体:机制、应用及展望
Diabetes Metab Syndr Obes. 2025 Aug 21;18:2955-2976. doi: 10.2147/DMSO.S532885. eCollection 2025.
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Diverse-Origin Exosomes Therapeutic Strategies for Diabetic Wound Healing.不同来源外泌体治疗糖尿病伤口愈合的策略
Int J Nanomedicine. 2025 Jun 12;20:7375-7402. doi: 10.2147/IJN.S519379. eCollection 2025.
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Exosomes: compositions, biogenesis, and mechanisms in diabetic wound healing.外泌体:在糖尿病创面愈合中的组成、发生机制和作用。
J Nanobiotechnology. 2024 Jul 5;22(1):398. doi: 10.1186/s12951-024-02684-1.
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Multifunctional ADM hydrogel containing endothelial cell-exosomes for diabetic wound healing.含内皮细胞外泌体的多功能ADM水凝胶用于糖尿病伤口愈合
Mater Today Bio. 2023 Nov 13;23:100863. doi: 10.1016/j.mtbio.2023.100863. eCollection 2023 Dec.