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  

作　　者：Tingwei Zhang Ziqi Chen Mengyuan Zhu Xuan Jing Xiaohui Xu Xulei Yuan Mengjiao Zhou Yanan Zhang Miao Lu Duanjing Chen Shihan Xu Jinlin Song 

机构地区：[1]Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences,Chongqing Municipal Key Laboratory for Oral Biomedical Engineering of Higher Education,and Stomatological Hospital of Chongqing Medical University,Chongqing 401147,China

出　　处：《Genes & Diseases》2023年第4期1613-1625,共13页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(No.81771082,81800985,82170968,31971282);the 2019 Chongqing Graduate Tutor Team Construction Project(No.dstd201903),China;the Natural Science Foundation of Chongqing(No.cstc2019jcyj-msxmX0851),China.

摘　　要：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 thera-peutic 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 ul-trasound(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 inten-sity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis.The stimuli increased the secretion of EVs by promoting the expres-sion of neutral sphingomyelinases in SCAP.In addition,EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of peri-odontal 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 produc-tion and efficacy.

关 键 词：Extracellular vesicles Low-intensity pulsed ultrasound Oral bone loss PERIODONTITIS Stem cells from apical papilla 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]