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 ...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.展开更多
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),Chinathe Natural Science Foundation of Chongqing(No.cstc2019jcyj-msxmX0851),China.
文摘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.