Promotion of osteochondral repair through immune microenvironment regulation and activation of endogenous chondrogenesis via the release of apoptotic vesicles from donor MSCs  

作　　者：Guangzhao Tian Han Yin Jinxuan Zheng Rongcheng Yu Zhengang Ding Zineng Yan Yiqi Tang Jiang Wu Chao Ning Xun Yuan Chenxi Liao Xiang Sui Zhe Zhao Shuyun Liu Weimin Guo Quanyi Guo 

机构地区：[1]School of Medicine,Nankai University,Tianjin,300071,China [2]Institute of Orthopedies,Department of Orthopedics,The Fourth Medical Center of PLA General Hospital,National Clinical Research Center for Orthopedics,Sports Medicine&Rehabilitation,51 Fucheng Road,Haidian District,Beijing,100142,China [3]Department of Orthopaedics,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China [4]Hospital of Stomatology,Guangdong Provincial Key Laboratory of Stomatology,Sun Yat-sen University,Guangzhou,510055,China [5]Department of Orthopaedic Surgery,Guangdong Provincial Key Laboratory of Orthopedics and Traumatology,First Affiliated Hospital Sun Yat-Sen University,Guangzhou,510080,China

出　　处：《Bioactive Materials》2024年第11期455-470,共16页生物活性材料（英文）

基　　金：Natural Science Foundation of Beijing Municipality(L234024);National Natural Science Foundation of China(82102552);Natural Science Foundation of Guangdong Province(2024A1515030295).

摘　　要：Utilizing transplanted human umbilical cord mesenchymal stem cells(HUMSCs)for cartilage defects yielded advanced tissue regeneration,but the underlying mechanism remain elucidated.Early after HUMSCs delivery to the defects,we observed substantial apoptosis.The released apoptotic vesicles(apoVs)of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment.ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs.Mechanistically,in macrophages,miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization.In MSCs,let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis.Consequently,a cell-free cartilage regeneration strategy using apoVs combined with a decellularized cartilage extracellular matrix(DCM)scaffold effectively promoted the regeneration of osteochondral defects.Overall,new mechanisms of cartilage regeneration by transplanted MSCs were unconcealed in this study.Moreover,we provided a novel experimental basis for cell-free tissue engineering-based cartilage regeneration utilizing apoVs.Utilizing transplanted human umbilical cord mesenchymal stem cells(HUMSCs)for cartilage defects yielded advanced tissue regeneration,but the underlying mechanism remain elucidated.Early after HUMSCs delivery to the defects,we observed substantial apoptosis.The released apoptotic vesicles(apoVs)of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment.ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs.Mechanistically,in macrophages,miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization.In MSCs,let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis.Consequently,a cell-free cartilage regeneration strategy using apoVs combined with a decel

关 键 词：Apoptotic vesicles Cartilage regeneration Human umbilical cord mesenchymal stem cells Macrophage polarization Tissue engineering 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]