Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium  

作　　者：Yong Zhang Jiayao Chen Haijun Fu Shuhong Kuang Feng He Min Zhang Zongshan Shen Wei Qin Zhengmei Lin Shuheng Huang 

机构地区：[1]Hospital of Stomatology,Guangdong Provincial Key Laboratory of Stomatology,Guanghua School of Stomatology,Sun Yat-sen University,Guangzhou,Guangdong,China [2]Guangzhou Digestive Disease Center,Guangzhou First People’s Hospital,School of Medicine,South China University of Technology,Guangzhou,Guangdong,China [3]The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,China [4]Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China

出　　处：《International Journal of Oral Science》2021年第4期448-462,共15页国际口腔科学杂志（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81873713,81700959 and 81873829);the International Cooperation Project of Science and Technology in Guangdong Province(Grant No.2016B050502008);the Natural Science Foundation of the Tibet Autonomous Region(XZ2019ZR-ZY64(Z)).

摘　　要：Although mesenchymal stem cell-derived exosomes(MSC-exos)have been shown to have therapeutic effects in experimental periodontitis,their drawbacks,such as low yield and limited efficacy,have hampered their clinical application.These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system.However,the potential function of MSC-exos produced by 3D culture(3D-exos)in periodontitis remains elusive.This study showed that compared with MSC-exos generated via 2D culture(2D-exos),3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17(Th17)cell/Treg balance in inflamed periodontal tissues.Mechanistically,3D-exos exhibited greater enrichment of miR-1246,which can suppress the expression of Nfat5,a key factor that mediates Th17 cell polarization in a sequence-dependent manner.Furthermore,we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis.Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis,the 3D culture system improved the function of MSC-exos in the treatment of periodontitis,but also it provided a basis for treating inflammatory bowel disease(IBD)by restoring immune responses in the inflamed periodontium.

关 键 词：period culture injection 

分 类 号：R781.42[医药卫生—口腔医学] R574.62[医药卫生—临床医学]