Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis.

Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis.
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DOI:
10.1016/j.gendis.2022.06.009
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发表时间:
2023-07
期刊:
影响因子:
6.8
通讯作者:
Song, Jinlin
Song, Jinlin
中科院分区:
医学2区
文献类型:
--
作者:
Zhang, Tingwei;Chen, Ziqi;Zhu, Mengyuan;Jing, Xuan;Xu, Xiaohui;Yuan, Xulei;Zhou, Mengjiao;Zhang, Yanan;Lu, Miao;Chen, Duanjing;Xu, Shihan;Song, Jinlin

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来源于间充质干细胞(MSC)的细胞外囊泡(EV)已成为一种新的细胞间串扰模式,并负责MSC的许多治疗效果。为了促进MSC-EV的应用,最近的研究集中在操纵MSC以提高EV的产生和EV介导的活性。本文详细介绍了一种使用无创低强度脉冲超声(LIPUS)作为刺激的优化方法,以提高口腔MSC-EV的产生和有效性。根尖乳头干细胞(SCAP),一种口腔间充质干细胞,显示强度依赖性的促成骨和抗炎反应,LIPUS没有显着的细胞毒性或凋亡。刺激通过促进SCAP中中性鞘磷脂酶的表达来增加EV的分泌。此外,LIPUS诱导的SCAP所产生的EV在体外促进牙周膜细胞的成骨分化和抗炎作用以及在体内减轻口腔炎性骨丢失方面表现出更强的功效。此外,LIPUS刺激影响SCAP-EV的物理特性和miRNA货物。进一步的研究表明,miR-935是LIPUS诱导的SCAP-EV的促成骨和抗炎能力的重要介质。总之,这些发现表明LIPUS是优化SCAP-EV生产和功效的简单有效的物理方法。
Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as a new mode of intercellular crosstalk and are responsible for many of the therapeutic effects of MSCs. To promote the application of MSC-EVs, recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities. The current paper details an optimization method using non-invasive low-intensity pulsed ultrasound (LIPUS) as the stimulation for improving oral MSC-EV production and effectiveness. Stem cells from apical papilla (SCAP), a type of oral mesenchymal stem cell, displayed intensity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis. The stimuli increased the secretion of EVs by promoting the expression of neutral sphingomyelinases in SCAP. In addition, EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of periodontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo. In addition, LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs. Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs. Taken together, these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV production and efficacy.
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