Amelioration of ligamentum flavum hypertrophy using umbilical cord mesenchymal stromal cell-derived extracellular vesicles
作者机构：Department of OrthopaedicsThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu210029China Department of Pathogen Biology and ImmunologyNanjing Medical UniversityNanjingJiangsu210029China Department of OrthopaedicsGeriatric Hospital of Nanjing Medical UniversityNanjingJiangsu210024China Outpatient&Emergency Management DepartmentThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Shenzhen Engineering Laboratory of Orthopaedic Regenerative TechnologiesDepartment of Spine SurgeryPeking University Shenzhen HospitalShenzhen518036China
出 版 物：《Bioactive Materials》 (生物活性材料（英文）)
年 卷 期：2023年第19卷第1期
页 面：139-154页
核心收录：
学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学]
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
主 题：Ligamentum flavum hypertrophy Fibrosis Umbilical cord mesenchymal stromal cells Extracellular vesicle miR-146a-5p miR-221-3p
摘 要：Ligamentum flavum(LF)hypertrophy(LFH)has been recognised as one of the key contributors to lumbar spinal ***,no effective methods are available to ameliorate this *** 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 *** downregulation of miR-146a-5p and miR-221-3p expressions in human LF tissues negatively correlated with increased LF *** 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 *** 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 ***,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 *** findings provide new insights into promising therapeutics using a hUCMSC-EVs-based delivery system for patients with lumbar spinal stenosis.
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