Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis:Toward a precision therapy
作者机构：Department of Sports MedicinePeking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhen518036China Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue RegenerationShanghai201306China Department of OrthopedicsShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200233China Department of OrthodonticsShanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghai200001China Shanghai Key Laboratory of Craniomaxillofacial Development and DiseasesFudan UniversityShanghai200001China Minhang HospitalFudan UniversityShanghai201199China
出 版 物：《Bioactive Materials》 (生物活性材料（英文）)
年 卷 期：2023年第30卷第12期
页 面：169-183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：the Key Project of National Natural Science Foundation of China(81830076) the National Natural Science Foundation of China(82272568) the Shanghai Engineering Technology Research Center and Professional Technology Service Platform project of 2020“Science and Technology Innovation Action Plan”of Shanghai(20DZ2254100) the Biomedical Technology Support Special Project of Shanghai 2021“Science and Technology Innovation Action Plan”(21S31902300)
主 题：Osteoarthritis Extracellular vesicles NLRP3 inflammasome Pyroptosis Cartilage-targeting
摘 要：Osteoarthritis(OA)is the most common disabling joint disease with no effective disease modifying *** vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models,representing a novel therapeutic *** this study,we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells(hUC-EVs)could maintain chondrocyte homeostasis and alleviate OA,and further revealed a novel molecular mechanism of this therapeutic ***-223,which could directly bind with the 3′UTR of NLRP3 mRNA,was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage *** enhancing the effect on mitigating osteoarthritis,exogenous miR-223 was loaded into hUC-EVs by electroporation,and a collagen II-targeting peptide(WYRGRL)was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the *** dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis,and offered excellent results for the treatment of *** study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.
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