Normal stress on surface of mesenchymal stem cells boosts extracellular vesicle secretion and regenerative bioactivity.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Chengmeng Bai, Huifang Ren, Feng Zhang, Dandan Li, Qingyu Feng, Ying Li, Ting Chen, Chengxu Li, Xuan Xiao, Hengrui Zhang, Liang Hu
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引用次数: 0

Abstract

Scalable approaches for enhancing therapeutic small extracellular vesicles (sEVs) production can facilitate the transition of sEVs from bench to bedside and beyond. Here, we present a user-friendly method to manipulate the extracellular mechanical microenvironment of umbilical cord-derived mesenchymal stem cells (MSCs), a promising cell type for generating sEVs with therapeutic benefits, to boost sEV secretion and regenerative bioactivity. The bioreactor system, called the programmable controlled rotating platform (PRP), is designed to apply normal stress on cell surface through centrifugal rotation culture. Experimental analyses suggested that the PRP can promote a 4-fold sEV secretion increase without affecting cell viability and sEV size when compared to the traditional static culture condition. More importantly, PRP-induced MSC-sEVs can significantly promote epithelial cell migration in vitro and accelerate corneal wound healing in a murine model, with suppressed inflammatory responses in wound bed tissue. Further mechanistic investigations revealed that this process involves the activation of cellular transcriptional signals implicated in sEV biogenesis. Concurrently, sEV cargo undergoes remodeling to enrich regenerative and immunoregulatory functions. These findings demonstrate the efficacy of our established platform in advancing sEV production and improving clinical performance, providing a novel sEV-based mechanism for ocular treatments, including corneal epithelialization and even retinal neural regeneration.

间充质干细胞表面正常应激可促进细胞外囊泡分泌和再生生物活性。
增强治疗性小细胞外囊泡(sev)产生的可扩展方法可以促进sev从实验室到床边甚至更远的过渡。在这里,我们提出了一种用户友好的方法来操纵脐带源性间充质干细胞(MSCs)的细胞外机械微环境,以促进sEV的分泌和再生生物活性。脐带源性间充质干细胞是一种有希望产生sEV并具有治疗益处的细胞类型。该生物反应器系统被称为可编程控制旋转平台(PRP),旨在通过离心旋转培养在细胞表面施加正应力。实验分析表明,与传统静态培养条件相比,PRP在不影响细胞活力和sEV大小的情况下,可使sEV分泌量增加4倍。更重要的是,prp诱导的msc - sev可以在体外显著促进上皮细胞的迁移,并在小鼠模型中加速角膜创面愈合,抑制创面组织的炎症反应。进一步的机制研究表明,这一过程涉及与sEV生物发生有关的细胞转录信号的激活。与此同时,sEV货运经历重塑以丰富再生和免疫调节功能。这些发现证明了我们建立的平台在促进sEV生产和提高临床表现方面的有效性,为角膜上皮化甚至视网膜神经再生等眼部治疗提供了一种新的sEV基础机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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