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

作者全名:"Zhang, Tingwei; Chen, Ziqi; Zhu, Mengyuan; Jing, Xuan; Xu, Xiaohui; Yuan, Xulei; Zhou, Mengjiao; Zhang, Yanan; Lu, Miao; Chen, Duanjing; Xu, Shihan; Song, Jinlin"

作者地址:"Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn High, Stomatol Hosp, Chongqing 401147, Peoples R China; Chongqing Med Univ, Stomatol Hosp, Chongqing 401147, Peoples R China"

通信作者:"Song, JL (通讯作者),Chongqing Med Univ, Stomatol Hosp, 426 Songshibei Rd, Chongqing 401147, Peoples R China."












关键词:Extracellular vesicles; Low -intensity pulsed; Oral bone loss; Periodontitis; Stem cells from apical; ultrasound; papilla

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 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 antiinflammatory capabilities of LIPUS-induced SCAP-EVs. Taken together, these findings"

基金机构:"National Natural Science Foundation of China [81771082, 81800985, 82170968, 31971282]; 2019 Chongqing Graduate Tutor Team Construction Project, China [dstd201903]; Natural Science Foundation of Chongqing, China [cstc2019jcyj-msxmX0851]"

基金资助正文:"This work was supported by the National Natural Science Foundation of China (No. 81771082, 81800985, 82170968, and 31971282); the 2019 Chongqing Graduate Tutor Team Construction Project (No. dstd201903), China; and the Natural Science Foundation of Chongqing (No. cstc2019jcyj-msxmX0851), China."