Amelioration of ligamentum flavum hypertrophy using umbilical cord mesenchymal stromal cell-derived extracellular vesicles  

作　　者：Cheng Ma Xin Qi Yi-Fan Wei Zhi Li He-Long Zhang He Li Feng-Lei Yu Ya-Nan Pu Yong-Can Huang Yong-Xin Ren 

机构地区：[1]Department of Orthopaedics,The First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu,210029,China [2]Department of Pathogen Biology and Immunology,Nanjing Medical University,Nanjing,Jiangsu,210029,China [3]Department of Orthopaedics,Geriatric Hospital of Nanjing Medical University,Nanjing,Jiangsu,210024,China [4]Outpatient&Emergency Management Department,The First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China [5]Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies,Department of Spine Surgery,Peking University Shenzhen Hospital,Shenzhen,518036,China

出　　处：《Bioactive Materials》2023年第1期139-154,共16页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(81572149,81600697);Guangdong Basic and Applied Basic Research Foundation(2021A1515220086);Basic Research Program of Jiangsu Province(Natural Science Foundation,K20201487);Jiangsu Province"333"Project(LGY2016001)and Sino-German Mobility programme of the Chinese-German Research Center of the National Science Foundation of China(NSFC)and the German Research Council(DFG),Grant Number M-0332.

摘　　要：Ligamentum flavum(LF)hypertrophy(LFH)has been recognised as one of the key contributors to lumbar spinal stenosis.Currently,no effective methods are available to ameliorate this hypertrophy.In this study,human umbilical cord mesenchymal stromal cell-derived extracellular vesicles(hUCMSC-EVs)were introduced for the first time as promising vehicles for drug delivery to treat LFH.The downregulation of miR-146a-5p and miR-221-3p expressions in human LF tissues negatively correlated with increased LF thickness.The hUCMSC-EVs enriched with these two miRNAs significantly suppressed LFH in vivo and notably ameliorated the progression of transforming growth factorβ1(TGF-β1)-induced fibrosis in vitro after delivering these two miRNAs to mouse LF cells.The results further demonstrated that miR-146a-5p and miR-221-3p directly bonded to the 3′-UTR regions of SMAD4 mRNA,thereby inhibiting the TGF-β/SMAD4 signalling pathway.Therefore,this translational study determined the effectiveness of a hUCMSC-EVs-based approach for the treatment of LFH and revealed the critical target of miR-146a-5p and miR-221-3p.Our findings provide new insights into promising therapeutics using a hUCMSC-EVs-based delivery system for patients with lumbar spinal stenosis.

关 键 词：Ligamentum flavum hypertrophy FIBROSIS Umbilical cord mesenchymal stromal cells Extracellular vesicle miR-146a-5p miR-221-3p 

分 类 号：R681[医药卫生—骨科学]