肿瘤组织来源的细胞外囊泡促进糖尿病创口愈合。
Tumor tissue derived extracellular vesicles promote diabetic wound healing.
发表日期:2023 Feb 20
作者:
Jiahe Guo, Guoyong Jiang, Jing Chen, Maojie Zhang, Kaituo Xiang, Cheng Wang, Tao Jiang, Yu Kang, Yue Sun, Xiang Xu, Xiaofan Yang, Zhenbing Chen
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
糖尿病性溃疡是当前一个重大的公共卫生挑战,其特征为过度产生反应性氧化物(ROS)。然而,目前糖尿病性溃疡治疗的可靠数据有限。肿瘤的生长已被证明具有与伤口愈合相似的特点。报道称乳腺癌来源的胞外囊泡(EVs)能促进细胞增殖、迁移和血管生成。来自肿瘤组织的EVs(tTi-EVs)具有原始组织的特征遗传,可能加速糖尿病性溃疡的愈合。我们想知道肿瘤来源的EVs是否能够加速糖尿病性溃疡的愈合。在本研究中,通过超离心和凝胶层析提取了来自乳腺癌组织的tTi-EVs。接下来,tTi-EVs扭转了H2O2所引起的成纤维细胞增殖和迁移的抑制作用。此外,tTi-EVs显著加速了伤口闭合、胶原沉积和新生血管形成,最终促进了糖尿病小鼠的伤口愈合。tTi-EVs还在体内外降低了氧化应激水平。此外,tTi-EVs的生物安全性通过血液检测和主要器官形态学分析已初步确认。总的来说,本研究证明tTi-EVs可以抑制氧化应激和促进糖尿病性溃疡愈合,提出了tTi-EVs的新功能,并为糖尿病性溃疡的治疗提供了潜在方案。版权所有©2023 Elsevier Inc.发布。
The diabetic wound nowadays remains a major public health challenge, which is characterized by overproduced reactive oxygen species (ROS). However, the current therapy for diabetic wounds is limited for reliable data in the general application. The growth of tumors has been revealed to share parallels with wound healing. Extracellular vesicles (EVs) derived from breast cancer have been reported to promote cell proliferation, migration and angiogenesis. The tumor tissue-derived EVs (tTi-EVs) of breast cancer performance a feature inheritance from original tissue and might accelerate the diabetic wound healing. We wonder whether the tumor-derived EVs are able to accelerate diabetic wound healing. In this study, tTi-EVs were extracted from breast cancer tissue via ultracentrifugation and size exclusion. Subsequently, tTi-EVs reversed the H2O2-induced inhibition of fibroblast proliferation and migration. Moreover, tTi-EVs significantly accelerated wound closure, collagen deposition and neovascularization, and finally promoted wound healing in diabetic mice. The tTi-EVs also reduced the level of oxidative stress in vitro and in vivo. Besides, the biosafety of tTi-EVs were preliminarily confirmed by blood tests and morphological analysis of major organs. Collectively, the present study proves that tTi-EVs can suppress oxidative stress and facilitate diabetic wound healing, which puts forward a novel function of tTi-EVs and provides potential treatment for diabetic wounds.Copyright © 2023. Published by Elsevier Inc.