{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:08:07Z","timestamp":1789474087274,"version":"build-2803163510"},"reference-count":157,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"A*STAR Career Development Award","award":["C210112047"],"award-info":[{"award-number":["C210112047"]}]},{"award":["C210112047"],"award-info":[{"award-number":["C210112047"]}],"id":[{"id":"https:\/\/ror.org\/02xjhr934","id-type":"ROR","asserted-by":"publisher"}]},{"name":"pre-gap funding","award":["I22D1AG050"],"award-info":[{"award-number":["I22D1AG050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent a promising cell-free therapeutic strategy for cartilage regeneration and inflammation modulation in degenerative and inflammatory musculoskeletal disorders, including osteoarthritis (OA), rheumatoid arthritis (RA) and intervertebral disc degeneration (IVDD). MSC-EVs enhance cartilage repair by promoting chondrocyte proliferation, migration, survival and extracellular matrix (ECM) synthesis to maintain cartilage homeostasis. In parallel, they exert anti-inflammatory and anti-catabolic effects by suppressing inflammatory cytokines, matrix-degrading enzymes, oxidative stress and inflammasome activation. In OA, MSC-EVs regulate chondrocyte function, ECM remodelling, immune responses and tissue regeneration by modulating multiple signalling pathways, including NF-\u03baB, PI3K\/AKT, MAPK, Wnt\/\u03b2-catenin and YAP signalling. In RA, MSC-EVs orchestrate innate and adaptive immune regulation, metabolic reprogramming and tissue repair pathways. In IVDD, MSC-EVs suppress chronic inflammation, reduce nucleus pulposus cell apoptosis, enhance cell proliferation and promote ECM synthesis, facilitating disc regeneration and functional restoration. Despite their therapeutic potential, several challenges hinder clinical translation. This review summarises current understanding of MSC-EV-mediated mechanisms in OA, RA and IVDD, and proposes strategies to enhance therapeutic efficacy and accelerate clinical application in musculoskeletal regenerative medicine.<\/jats:p>","DOI":"10.3390\/ijms27188208","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:57:34Z","timestamp":1789473454000},"page":"8208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MSC-EVs in Cartilage Regeneration and Immunomodulation: Mechanisms and Therapeutic Prospects for Osteoarthritis, Rheumatoid Arthritis and Intervertebral Disc Degeneration"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9969-1694","authenticated-orcid":false,"given":"Tong Ming","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Singapore 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108197","DOI":"10.4252\/wjsc.v17.i6.108197","article-title":"Mesenchymal stem cell-derived extracellular vesicles: Pioneering the next generation of biomedical applications","volume":"17","author":"Liu","year":"2025","journal-title":"World J. Stem Cells"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/s41419-025-08094-x","article-title":"Understanding the molecular basis of mesenchymal stem cell stemness: Implications for clinical applications","volume":"16","author":"Liu","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2202453","DOI":"10.1002\/adhm.202202453","article-title":"Deciphering the Heterogeneity Landscape of Mesenchymal Stem\/Stromal Cell-Derived Extracellular Vesicles for Precise Selection in Translational Medicine","volume":"12","author":"Li","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.semcdb.2016.11.008","article-title":"MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment","volume":"67","author":"Toh","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/stem.2575","article-title":"Concise Review: MSC-Derived Exosomes for Cell-Free Therapy","volume":"35","author":"Phinney","year":"2017","journal-title":"Stem Cells"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12951-024-02603-4","article-title":"Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics","volume":"22","author":"Yang","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s10561-024-10150-3","article-title":"Adipose-mesenchymal stem cell-derived extracellular vesicles enhance angiogenesis and skin wound healing via bFGF-mediated VEGF expression","volume":"26","author":"Ding","year":"2024","journal-title":"Cell Tissue Bank."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.actbio.2021.02.039","article-title":"The tissue origin effect of extracellular vesicles on cartilage and bone regeneration","volume":"125","author":"Li","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13287-017-0510-9","article-title":"Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis","volume":"8","author":"Zhu","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e177841","DOI":"10.1172\/jci.insight.177841","article-title":"miRNA-148a-containing GMSC-derived EVs modulate Treg\/Th17 balance via IKKB\/NF-kappaB pathway and treat a rheumatoid arthritis model","volume":"9","author":"Chen","year":"2024","journal-title":"JCI Insight"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1186\/s13287-021-02362-1","article-title":"Induced pluripotent stem cell-derived mesenchymal stem cells deliver exogenous miR-105-5p via small extracellular vesicles to rejuvenate senescent nucleus pulposus cells and attenuate intervertebral disc degeneration","volume":"12","author":"Sun","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1186\/s13287-025-04585-y","article-title":"Ontogenetic stage and type of donor cells shape extracellular vesicles\u2019 therapeutic potential for osteoarthritis","volume":"16","author":"Tarasova","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13776","DOI":"10.1111\/cpr.13776","article-title":"Comparative Analysis of the Therapeutic Potential of Extracellular Vesicles Secreted by Aged and Young Bone Marrow-Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis","volume":"58","author":"Wakale","year":"2025","journal-title":"Cell Prolif."},{"key":"ref_15","first-page":"98","article-title":"Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles","volume":"27","author":"Yang","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.joca.2022.07.012","article-title":"Cellular therapy and tissue engineering for cartilage repair","volume":"30","author":"Zelinka","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1002\/art.30430","article-title":"Zinc-finger protein 145, acting as an upstream regulator of SOX9, improves the differentiation potential of human mesenchymal stem cells for cartilage regeneration and repair","volume":"63","author":"Liu","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41419-022-05034-x","article-title":"Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: A next generation therapeutic tool?","volume":"13","author":"Kou","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16214","DOI":"10.1038\/s41598-017-15376-8","article-title":"Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis","volume":"7","author":"Cosenza","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1080\/21655979.2021.1995580","article-title":"miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis","volume":"12","author":"Xia","year":"2021","journal-title":"Bioengineered"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/cbin.11657","article-title":"Exosomes from human umbilical cord mesenchymal stem cells inhibit ROS production and cell apoptosis in human articular chondrocytes via the miR-100-5p\/NOX4 axis","volume":"45","author":"Li","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1002\/ctm2.255","article-title":"The umbilical cord mesenchymal stem cell-derived exosomal lncRNA H19 improves osteochondral activity through miR-29b-3p\/FoxO3 axis","volume":"11","author":"Yan","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12951-024-02451-2","article-title":"HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1\/TGF-beta\/Smad2\/3 axis mediated by microfractures","volume":"22","author":"Chen","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1157498","DOI":"10.1155\/2022\/1157498","article-title":"Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression","volume":"2022","author":"Zhang","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1186\/s13287-025-04679-7","article-title":"Extracellular vesicles from primed Hoffa\u2019s fat pad mesenchymal stem\/stromal cells in osteoarthritis therapy: Effects on cells critical to osteoarthritis progression","volume":"16","author":"Gulova","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.biomaterials.2017.11.028","article-title":"MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity","volume":"156","author":"Zhang","year":"2018","journal-title":"Biomaterials"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1177\/03635465211068129","article-title":"Mesenchymal Stem Cell Exosomes Promote Functional Osteochondral Repair in a Clinically Relevant Porcine Model","volume":"50","author":"Zhang","year":"2022","journal-title":"Am. J. Sports Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.joca.2016.06.022","article-title":"Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration","volume":"24","author":"Zhang","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s00590-025-04284-7","article-title":"Comparative analysis of the therapeutic effects of mesenchymal stem cells and exosomes on cartilage regeneration: Exploring their synergistic potential with hyaluronic acid for treating articular cartilage defects","volume":"35","author":"Meric","year":"2025","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s12015-025-10853-4","article-title":"Evaluation of the Safety and Regenerative Potential of Human Mesenchymal Stem Cells and Their Extracellular Vesicles in a Transgenic Pig Model of Cartilage-Bone Injury In Vivo\u2014Preclinical Study","volume":"21","author":"Wieczorek","year":"2025","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, X.H., Chen, S.Y., Zhou, Q.F., and Cai, Y.Z. (2025). Exosomes in Osteoarthritis: Breakthrough Innovations and Advanced Tissue Engineering for Cartilage Regeneration Since 2020. Biomedicines, 13.","DOI":"10.3390\/biomedicines13102486"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.omtn.2020.09.014","article-title":"Synovial Mesenchymal Stem Cell-Derived EV-Packaged miR-31 Downregulates Histone Demethylase KDM2A to Prevent Knee Osteoarthritis","volume":"22","author":"Wang","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1186\/s13075-020-02325-6","article-title":"Mesenchymal stem cell-derived exosomal microRNA-136-5p inhibits chondrocyte degeneration in traumatic osteoarthritis by targeting ELF3","volume":"22","author":"Chen","year":"2020","journal-title":"Arthrit. Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103974","DOI":"10.1016\/j.identj.2025.103974","article-title":"Dental Pulp Stem Cell-Derived Intracellular Vesicles Promote Cartilage Regeneration and Alleviate Pain in Temporomandibular Joint Osteoarthritis","volume":"76","author":"Shu","year":"2026","journal-title":"Int. Dent. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"121952","DOI":"10.1016\/j.ijpharm.2022.121952","article-title":"Wharton\u2019s jelly mesenchymal stem cell-derived small extracellular vesicles as natural nanoparticles to attenuate cartilage injury via microRNA regulation","volume":"623","author":"Chen","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1186\/s13287-021-02481-9","article-title":"Extracellular vesicles derived from mesenchymal stromal cells mediate endogenous cell growth and migration via the CXCL5 and CXCL6\/CXCR2 axes and repair menisci","volume":"12","author":"Kawata","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101056","DOI":"10.1016\/j.reth.2025.101056","article-title":"Extracellular vesicles derived from adipose-derived mesenchymal stem\/stromal cells prevent synovial inflammation and attenuate cartilage degeneration in rodent osteoarthritis","volume":"31","author":"Maruiwa","year":"2026","journal-title":"Regen. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103157","DOI":"10.1016\/j.tice.2025.103157","article-title":"MSC-derived exosomes promote chondrocyte proliferation and inhibit apoptosis by suppressing inflammation in osteoarthritis","volume":"98","author":"Ji","year":"2026","journal-title":"Tissue Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e3379","DOI":"10.1002\/jgm.3379","article-title":"Synovial mesenchymal stem cell-derived extracellular vesicles containing microRN555A-26a-5p ameliorate cartilage damage of osteoarthritis","volume":"23","author":"Lu","year":"2021","journal-title":"J. Gene Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1042\/BCJ20180675","article-title":"Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis","volume":"475","author":"Liu","year":"2018","journal-title":"Biochem. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9972805","DOI":"10.1155\/2021\/9972805","article-title":"BMSC-Derived Exosomes Ameliorate Osteoarthritis by Inhibiting Pyroptosis of Cartilage via Delivering miR-326 Targeting HDAC3 and STAT1\/\/NF-kappaB p65 to Chondrocytes","volume":"2021","author":"Xu","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s13770-024-00668-8","article-title":"Exosomes-Shuttled lncRNA SNHG7 by Bone Marrow Mesenchymal Stem Cells Alleviates Osteoarthritis Through Targeting miR-485-5p\/FSP1 Axis-Mediated Chondrocytes Ferroptosis and Inflammation","volume":"21","author":"Wang","year":"2024","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e70811","DOI":"10.1096\/fj.202501185R","article-title":"Adipose Mesenchymal Stem Cells Derived Exosomes Ameliorates KOA Cartilage Damage and Inflammation by Activation of PINK1-Mediated Mitochondrial Autophagy","volume":"39","author":"Kang","year":"2025","journal-title":"FASEB J."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wu, C.W., Huang, Y.H., Shao, P.L., Chang, L.H., Lu, C.C., Chen, C.H., Fu, Y.C., Ho, M.L., Chang, J.K., and Wu, S.C. (2025). Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Enhance Chondrocyte Function by Reducing Oxidative Stress in Chondrocytes. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26167683"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113954","DOI":"10.1016\/j.intimp.2024.113954","article-title":"Mitochondria-rich extracellular vesicles derived from the culture supernatant of human synovial Fluid-derived mesenchymal stem cells Inhibited senescence of Stressed\/inflammatory Licensed chondrocytes and Delayed Osteoarthritis progression","volume":"147","author":"Li","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/stcltm\/szae031","article-title":"Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models","volume":"13","author":"Yang","year":"2024","journal-title":"Stem Cells Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13287-017-0632-0","article-title":"Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix","volume":"8","author":"Wang","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104978","DOI":"10.1016\/j.bioorg.2021.104978","article-title":"Human bone mesenchymal stem cells-derived exosomal miRNA-361-5p alleviates osteoarthritis by downregulating DDX20 and inactivating the NF-kappaB signaling pathway","volume":"113","author":"Tao","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9455152","DOI":"10.1155\/2022\/9455152","article-title":"miR-3960 from Mesenchymal Stem Cell-Derived Extracellular Vesicles Inactivates SDC1\/Wnt\/beta-Catenin Axis to Relieve Chondrocyte Injury in Osteoarthritis by Targeting PHLDA2","volume":"2022","author":"Ye","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1089\/dna.2023.0341","article-title":"Exosomes Derived from Quercetin-Treated Bone Marrow Derived Mesenchymal Stem Cells Inhibit the Progression of Osteoarthritis Through Delivering miR-124-3p to Chondrocytes","volume":"43","author":"Dong","year":"2024","journal-title":"DNA Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"180","DOI":"10.7150\/thno.17133","article-title":"Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model","volume":"7","author":"Tao","year":"2017","journal-title":"Theranostics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"25138","DOI":"10.18632\/aging.104110","article-title":"Bone marrow mesenchymal stem cell-derived exosomes prevent osteoarthritis by regulating synovial macrophage polarization","volume":"12","author":"Zhang","year":"2020","journal-title":"Aging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5517648","DOI":"10.1155\/2022\/5517648","article-title":"Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Containing Long Noncoding RNA NEAT1 Relieve Osteoarthritis","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.24976\/Discov.Med.202436186.132","article-title":"The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of circYAP1\/miRNA-21\/TLR7 Axis","volume":"36","author":"Aboulhoda","year":"2024","journal-title":"Discov. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s12951-021-00940-2","article-title":"Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3\/miR-124-3p\/MYH9 axis","volume":"19","author":"Li","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12951-024-03088-x","article-title":"Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: Preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis","volume":"23","author":"Garcia","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12951-021-01236-1","article-title":"Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages","volume":"20","author":"Li","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00441-020-03319-1","article-title":"TGF-beta1-modified MSC-derived exosomal miR-135b attenuates cartilage injury via promoting M2 synovial macrophage polarization by targeting MAPK6","volume":"384","author":"Wang","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_59","first-page":"3","article-title":"MSC secretome from amniotic fluid halts IL-1beta and TNF-alpha inflammation via the ERK\/MAPK pathway, promoting cartilage regeneration in OA in vitro","volume":"20","author":"Klaymook","year":"2024","journal-title":"J. Stem Cells Regen. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1186\/s12951-024-02711-1","article-title":"Adipose-derived stem cell exosomes loaded with icariin alleviates rheumatoid arthritis by modulating macrophage polarization in rats","volume":"22","author":"Yan","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11626-019-00330-x","article-title":"Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways","volume":"55","author":"Qi","year":"2019","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s13287-023-03523-0","article-title":"Exosomes derived from mesenchymal stem cells primed with disease-condition-serum improved therapeutic efficacy in a mouse rheumatoid arthritis model via enhanced TGF-beta1 production","volume":"14","author":"Choi","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.freeradbiomed.2025.02.027","article-title":"Exosomes inhibit ferroptosis to alleviate intervertebral disc degeneration via the p62-KEAP1-NRF2 pathway","volume":"232","author":"Chen","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"112109","DOI":"10.1016\/j.yexcr.2020.112109","article-title":"Exosomal miR-532-5p from bone marrow mesenchymal stem cells reduce intervertebral disc degeneration by targeting RASSF5","volume":"393","author":"Zhu","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2310025","DOI":"10.1155\/2021\/2310025","article-title":"Exosomes Derived from Bone Mesenchymal Stem Cells Alleviate Compression-Induced Nucleus Pulposus Cell Apoptosis by Inhibiting Oxidative Stress","volume":"2021","author":"Hu","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1007\/s12015-024-10781-9","article-title":"Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Nuclear Pulposus Cells Degeneration Through the miR-145a-5p\/USP31\/HIF-1alpha Signaling Pathway","volume":"20","author":"Su","year":"2024","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e04347","DOI":"10.1002\/advs.202504347","article-title":"Human iPSCs Derived MSCs-Secreted Exosomes Modulate Senescent Nucleus Pulposus Cells Induced Macrophage Polarization via Metabolic Reprogramming to Mitigate Intervertebral Disc Degeneration","volume":"12","author":"Xiang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2019.07.026","article-title":"Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects","volume":"143","author":"Xia","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.3724\/abbs.2023241","article-title":"Mesenchymal stem cell exosomes inhibit nucleus pulposus cell apoptosis via the miR-125b-5p\/TRAF6\/NF-kappaB pathway axis","volume":"55","author":"Duan","year":"2023","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s13287-022-03005-9","article-title":"Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage","volume":"13","author":"Zhou","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Klyucherev, T.O., Peshkova, M.A., Revokatova, D.P., Serejnikova, N.B., Fayzullina, N.M., Fayzullin, A.L., Ershov, B.P., Khristidis, Y.I., Vlasova, I.I., and Kosheleva, N.V. (2024). The Therapeutic Potential of Exosomes vs. Matrix-Bound Nanovesicles from Human Umbilical Cord Mesenchymal Stromal Cells in Osteoarthritis Treatment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111564"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s13770-025-00716-x","article-title":"Exosomes Extracted from Human Umbilical Cord MSCs Contribute to Osteoarthritic Cartilage and Chondrocytes Repair Through Enhancing Autophagy While Suppressing the Wnt\/beta-Catenin Pathway","volume":"22","author":"Qin","year":"2025","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biomaterials.2019.02.006","article-title":"MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis","volume":"200","author":"Zhang","year":"2019","journal-title":"Biomaterials"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"34928","DOI":"10.1021\/acsnano.5c11211","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Temporomandibular Joint Osteoarthritis by Suppressing Osteoclast Activity Via let-7a-5p\/Integrin beta3 Axis","volume":"19","author":"Yang","year":"2025","journal-title":"ACS Nano"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"151933","DOI":"10.1016\/j.acthis.2022.151933","article-title":"TGFbeta1-modified MSC-derived exosome attenuates osteoarthritis by inhibiting PDGF-BB secretion and H-type vessel activity in the subchondral bone","volume":"124","author":"Wang","year":"2022","journal-title":"Acta Histochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.joca.2022.08.009","article-title":"Extracellular vesicles derived from mesenchymal stem cells confer protection against intervertebral disc degeneration through a microRNA-217-dependent mechanism","volume":"30","author":"Hao","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Piazza, N., Dehghani, M., Gaborski, T.R., and Wuertz-Kozak, K. (2020). Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00311"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.actbio.2026.05.036","article-title":"Bioengineered MSC-Derived Extracellular Vesicles in Intervertebral Disc Therapeutics: A Systematic Review","volume":"218","author":"Martins","year":"2026","journal-title":"Acta Biomater."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13287-020-01781-w","article-title":"Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis","volume":"11","author":"He","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"118987","DOI":"10.1016\/j.lfs.2020.118987","article-title":"MiR-129-5p shuttled by human synovial mesenchymal stem cell-derived exosomes relieves IL-1beta induced osteoarthritis via targeting HMGB1","volume":"269","author":"Qiu","year":"2021","journal-title":"Life Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"114916","DOI":"10.1016\/j.intimp.2025.114916","article-title":"Exosomal miR-574-3p from adipose-derived mesenchymal stem modulates CRIM1\/BMPs signaling to restrain chondrocytes hypertrophy and inflammatory response in knee osteoarthritis","volume":"159","author":"Kang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhao, M., Li, W., Yang, Y., Zhang, Z., Ma, R., and Wu, M. (2021). BMSC-Derived Small Extracellular Vesicles Induce Cartilage Reconstruction of Temporomandibular Joint Osteoarthritis via Autotaxin-YAP Signaling Axis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.656153"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhang, B., Lai, R.C., Sim, W.K., and Lim, S.K. (2023). Therapeutic Efficacy of Mesenchymal Stem\/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance. Biomolecules, 13.","DOI":"10.3390\/biom13101501"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1021\/acs.jproteome.3c00697","article-title":"Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Rheumatoid Arthritis Symptoms via Shuttling Proteins","volume":"23","author":"Wang","year":"2024","journal-title":"J. Proteome Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2948090","DOI":"10.1155\/2022\/2948090","article-title":"circ_0072464 Shuttled by Bone Mesenchymal Stem Cell-Secreted Extracellular Vesicles Inhibits Nucleus Pulposus Cell Ferroptosis to Relieve Intervertebral Disc Degeneration","volume":"2022","author":"Yu","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"11742","DOI":"10.1111\/jcmm.15784","article-title":"Mesenchymal stem cells-derived exosomes ameliorate intervertebral disc degeneration through inhibiting pyroptosis","volume":"24","author":"Zhang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/jcmm.13316","article-title":"Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration","volume":"22","author":"Cheng","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1097\/CORR.0000000000003067","article-title":"Human Infrapatellar Fat Pad Mesenchymal Stem Cell-derived Extracellular Vesicles Purified by Anion Exchange Chromatography Suppress Osteoarthritis Progression in a Mouse Model","volume":"482","author":"Liu","year":"2024","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/s13287-020-01832-2","article-title":"Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures","volume":"11","author":"Hingert","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"8825332","DOI":"10.1155\/2021\/8825332","article-title":"Functional Properties of Human-Derived Mesenchymal Stem Cell Spheroids: A Meta-Analysis and Systematic Review","volume":"2021","author":"Ezquerra","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e07073","DOI":"10.1002\/smll.202507073","article-title":"Spheroid-Derived BMSC Exosomes Enhance Proliferation and Matrix Remodeling of Nucleus Pulposus Cell Clusters in Degenerative Disc Repair","volume":"21","author":"Li","year":"2025","journal-title":"Small"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10565-019-09504-5","article-title":"Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity","volume":"36","author":"Yan","year":"2020","journal-title":"Cell Biol. Toxicol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"025021","DOI":"10.1088\/1748-605X\/adb22e","article-title":"Three-dimensional cell culture-derived extracellular vesicles loaded alginate\/hyaluronic acid composite scaffold as an optimal therapy for cartilage defect regeneration","volume":"20","author":"Zhang","year":"2025","journal-title":"Biomed. Mater."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s12951-022-01339-3","article-title":"Curcumin primed ADMSCs derived small extracellular vesicle exert enhanced protective effects on osteoarthritis by inhibiting oxidative stress and chondrocyte apoptosis","volume":"20","author":"Xu","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_96","unstructured":"Chen, K., Mei, S., and Zhang, P. (2026). Curcumin enhances the protective effect of bone marrow mesenchymal stem cell-derived extracellular vesicles in alleviating intervertebral disc degeneration. Histol. Histopathol., 25098."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/s13018-025-05785-1","article-title":"Quercetin-primed MSC exosomes synergistically attenuate osteoarthritis progression","volume":"20","author":"Lu","year":"2025","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.7150\/ijms.126119","article-title":"Artemisia argyi-enhanced Mesenchymal Stem Cell Exosomes Alleviates Inflammation in C28\/I2 Chondrocytes by inhibiting NF-kappaB","volume":"23","author":"Kao","year":"2026","journal-title":"Int. J. Med. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"126367","DOI":"10.1016\/j.ijpharm.2025.126367","article-title":"NMN-primed exosomes derived from infrapatellar fat pad mesenchymal stem cells exert synergistic anti-inflammatory and cartilage-protective effects via MERTK pathway activation in knee osteoarthritis","volume":"687","author":"Chen","year":"2026","journal-title":"Int. J. Pharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1186\/s12951-024-02795-9","article-title":"Engineering exosomes derived from TNF-alpha preconditioned IPFP-MSCs enhance both yield and therapeutic efficacy for osteoarthritis","volume":"22","author":"Wu","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13287-020-01677-9","article-title":"Inflammatory priming enhances mesenchymal stromal cell secretome potential as a clinical product for regenerative medicine approaches through secreted factors and EV-miRNAs: The example of joint disease","volume":"11","author":"Ragni","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"152391","DOI":"10.1016\/j.bbrc.2025.152391","article-title":"Inflammatory priming of mesenchymal stromal cells enhances its secretome potential through secretion of anti-inflammatory and ECM modulating factors: Insights into proteomic and functional properties","volume":"778","author":"Joshi","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4924","DOI":"10.1021\/acsnano.4c16785","article-title":"Remodeling the Proinflammatory Microenvironment in Osteoarthritis through Interleukin-1 Beta Tailored Exosome Cargo for Inflammatory Regulation and Cartilage Regeneration","volume":"19","author":"Chen","year":"2025","journal-title":"ACS Nano"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1186\/s13287-021-02507-2","article-title":"Extracellular vesicles derived from LPS-preconditioned human synovial mesenchymal stem cells inhibit extracellular matrix degradation and prevent osteoarthritis of the knee in a mouse model","volume":"12","author":"Duan","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s13770-024-00663-z","article-title":"Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants","volume":"21","author":"Peng","year":"2024","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"112028","DOI":"10.1016\/j.intimp.2024.112028","article-title":"Selenomethionine preconditioned mesenchymal stem cells derived extracellular vesicles exert enhanced therapeutic efficacy in intervertebral disc degeneration","volume":"132","author":"Ma","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"20417314251351011","DOI":"10.1177\/20417314251351011","article-title":"Amelioration of intervertebral disc degeneration using engineered extracellular vesicle-delivered ZDHHC5 via inhibiting PANoptosis","volume":"16","author":"Chen","year":"2025","journal-title":"J. Tissue Eng."},{"key":"ref_108","first-page":"555","article-title":"Microenvironment-educated MSC-EVs loaded injectable smart hydrogel for targeting senescent nucleus pulposus cells and inhibiting ferroptosis against intervertebral disc degeneration","volume":"61","author":"Wu","year":"2026","journal-title":"Bioact. Mater."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.actbio.2020.12.034","article-title":"Hypoxic pretreatment of small extracellular vesicles mediates cartilage repair in osteoarthritis by delivering miR-216a-5p","volume":"122","author":"Rong","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s13287-025-04412-4","article-title":"Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism","volume":"16","author":"Zhang","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Zhang, B., Tian, X., Qu, Z., Hao, J., and Zhang, W. (2022). Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis. Membranes, 12.","DOI":"10.3390\/membranes12020225"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e2404275","DOI":"10.1002\/advs.202404275","article-title":"Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration","volume":"11","author":"Jin","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Ulpiano, C., da Silva, C.L., and Monteiro, G.A. (2023). Bioengineered Mesenchymal-Stromal-Cell-Derived Extracellular Vesicles as an Improved Drug Delivery System: Methods and Applications. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041231"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"255","DOI":"10.20517\/evcna.2023.21","article-title":"Opportunities for engineering outer membrane vesicles using synthetic biology approaches","volume":"4","author":"Kelwick","year":"2023","journal-title":"Extracell. Vesicles Circ. Nucleic Acids"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s13287-018-1004-0","article-title":"Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A","volume":"9","author":"Mao","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e2304194","DOI":"10.1002\/adhm.202304194","article-title":"Engineered hsa-miR-455-3p-Abundant Extracellular Vesicles Derived from 3D-Cultured Adipose Mesenchymal Stem Cells for Tissue-Engineering Hyaline Cartilage Regeneration","volume":"13","author":"Chen","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1177\/03635465221073991","article-title":"Exosomes Derived From Human Urine-Derived Stem Cells Overexpressing miR-140-5p Alleviate Knee Osteoarthritis Through Downregulation of VEGFA in a Rat Model","volume":"50","author":"Liu","year":"2022","journal-title":"Am. J. Sports Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"124024","DOI":"10.1016\/j.biomaterials.2026.124024","article-title":"A synergistic strategy involving reverse-adaptation and engineered MSC exosomes against ferroptosis in osteoarthritis","volume":"330","author":"Wang","year":"2026","journal-title":"Biomaterials"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1089\/scd.2020.0083","article-title":"Exosomes Derived from Human Placental Mesenchymal Stromal Cells Carrying AntagomiR-4450 Alleviate Intervertebral Disc Degeneration Through Upregulation of ZNF121","volume":"29","author":"Yuan","year":"2020","journal-title":"Stem Cells Dev."},{"key":"ref_120","first-page":"578","article-title":"The Role of Extracellular Vesicles Derived from MicroRNA-146a-modified Mesenchymal Stem Cells in Modulating Inflammation in Experimental Glenohumeral Osteoarthritis","volume":"23","author":"Cao","year":"2024","journal-title":"Iran. J. Allergy Asthma Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Wu, K.C., Yang, H.I., Chang, Y.H., Chiang, R.Y., and Ding, D.C. (2025). Extracellular Vesicles Derived from Human Umbilical Mesenchymal Stem Cells Transfected with miR-7704 Improved Damaged Cartilage and Reduced Matrix Metallopeptidase 13. Cells, 14.","DOI":"10.3390\/cells14020082"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"20417314241312563","DOI":"10.1177\/20417314241312563","article-title":"Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells","volume":"16","author":"Wang","year":"2025","journal-title":"J. Tissue Eng."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"145092","DOI":"10.1016\/j.ijbiomac.2025.145092","article-title":"Apoptosis linked gene-2 interacting protein X as a target to regulate the yield of small extracellular vesicles derived from tissue specific mesenchymal stem cells for translational applications","volume":"318","author":"Sharma","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e202400611","DOI":"10.1002\/biot.202400611","article-title":"tsRNA-12391-Modified Adipose Mesenchymal Stem Cell-Derived Exosomes Mitigate Cartilage Degeneration in Osteoarthritis by Enhancing Mitophagy","volume":"20","author":"Shi","year":"2025","journal-title":"Biotechnol. J."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Pan, C., Huang, W., Chen, Q., Xu, J., Yao, G., Li, B., Wu, T., Yin, C., and Cheng, X. (2021). LncRNA Malat-1 From MSCs-Derived Extracellular Vesicles Suppresses Inflammation and Cartilage Degradation in Osteoarthritis. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.772002"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1080\/15384101.2018.1526603","article-title":"MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1\/miR-206\/GIT1 axis in osteoarthritis","volume":"17","author":"Liu","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1089\/scd.2012.0222","article-title":"Molecular basis of immortalization of human mesenchymal stem cells by combination of p53 knockdown and human telomerase reverse transcriptase overexpression","volume":"22","author":"Liu","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.stemcr.2020.01.002","article-title":"Ascorbate and Iron Are Required for the Specification and Long-Term Self-Renewal of Human Skeletal Mesenchymal Stromal Cells","volume":"14","author":"Liu","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4252\/wjsc.v16.i2.191","article-title":"Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a","volume":"16","author":"Yang","year":"2024","journal-title":"World J. Stem Cells"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., Lee, S.Y., Cha, S.G., Park, J.M., Song, D.H., Lee, S.H., Hwang, D.Y., Kim, B.J., Rho, S., and Park, C.G. (2024). Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105242"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2413759","DOI":"10.1002\/advs.202413759","article-title":"Engineered MSC-sEVs as a Versatile Nanoplatform for Enhanced Osteoarthritis Treatment via Targeted Elimination of Senescent Chondrocytes and Maintenance of Cartilage Matrix Metabolic Homeostasis","volume":"12","author":"Feng","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"42658","DOI":"10.1021\/acsami.5c06750","article-title":"Engineered EVs from 3D-Cultured MSCs for Synergistic Modulation of Inflammatory Microenvironment and Cartilage Regeneration in Osteoarthritis","volume":"17","author":"Fu","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"33937","DOI":"10.1021\/acsnano.4c07992","article-title":"Hybrid Nanoparticle Engineered with Transforming Growth Factor -beta1-Overexpressed Extracellular Vesicle and Cartilage-Targeted Anti-Inflammatory Liposome for Osteoarthritis","volume":"18","author":"Kim","year":"2024","journal-title":"ACS Nano"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12951-026-04142-6","article-title":"Bioengineering of extracellular vesicles with scaffold proteins for drug delivery","volume":"24","author":"Zhang","year":"2026","journal-title":"J. Nanobiotechnol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Wu, K.C., Chang, Y.H., Chiang, R.Y., and Ding, D.C. (2025). CAP-LAMP2b-Modified Stem Cells\u2019 Extracellular Vesicles Hybrid with CRISPR-Cas9 Targeting ADAMTS4 to Reverse IL-1beta-Induced Aggrecan Loss in Chondrocytes. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199812"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jconrel.2016.01.009","article-title":"PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time","volume":"224","author":"Kooijmans","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12951-018-0388-4","article-title":"Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display","volume":"16","author":"Antes","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"21933","DOI":"10.1038\/srep21933","article-title":"Engineering hybrid exosomes by membrane fusion with liposomes","volume":"6","author":"Sato","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1039\/D6BM00356G","article-title":"Liposome-extracellular vesicle hybrid nanocarriers: Design principles, interfacial properties and translational perspectives","volume":"14","author":"Huang","year":"2026","journal-title":"Biomater. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1016\/j.apsb.2025.06.009","article-title":"Artificial mesenchymal stem cell extracellular vesicles enhanced ischemic stroke treatment through targeted remodeling brain microvascular endothelial cells","volume":"15","author":"Li","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"55767","DOI":"10.1021\/acsami.1c08044","article-title":"Extruded Mesenchymal Stem Cell Nanovesicles Are Equally Potent to Natural Extracellular Vesicles in Cardiac Repair","volume":"13","author":"Wang","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"7248","DOI":"10.1007\/s12274-023-5374-3","article-title":"Comparison of extruded cell nanovesicles and exosomes in their molecular cargos and regenerative potentials","volume":"16","author":"Wang","year":"2023","journal-title":"Nano Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1002\/jex2.70","article-title":"GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology","volume":"1","author":"Lau","year":"2022","journal-title":"J. Extracell. Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e2300319","DOI":"10.1002\/adhm.202300319","article-title":"A Comparison of Cellular Uptake Mechanisms, Delivery Efficacy, and Intracellular Fate between Liposomes and Extracellular Vesicles","volume":"12","author":"Gandek","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1039\/D4BM01405G","article-title":"Hybrid lipid nanoparticles derived from human mesenchymal stem cell extracellular vesicles by microfluidic sonication for collagen I mRNA delivery to human tendon progenitor stem cells","volume":"13","author":"Lamparelli","year":"2025","journal-title":"Biomater. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.actbio.2021.01.010","article-title":"Biomaterial-based extracellular vesicle delivery for therapeutic applications","volume":"124","author":"Murali","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e71210","DOI":"10.1002\/adhm.71210","article-title":"A Hydrogel-Mediated Sustained-Release Platform Alters the Biodistribution of Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Mice","volume":"15","author":"Sun","year":"2026","journal-title":"Adv. Healthc. Mater."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jconrel.2019.11.003","article-title":"Injectable extracellular vesicle-released self-assembling peptide nanofiber hydrogel as an enhanced cell-free therapy for tissue regeneration","volume":"316","author":"Zhou","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"16071","DOI":"10.1038\/natrevmats.2016.71","article-title":"Designing hydrogels for controlled drug delivery","volume":"1","author":"Li","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"102748","DOI":"10.1016\/j.nano.2024.102748","article-title":"Pluronic F127 hydrogel-loaded extracellular vesicles from adipose-derived mesenchymal stem cells promote tracheal cartilage regeneration via SCNN1B delivery","volume":"58","author":"Guo","year":"2024","journal-title":"Nanomedicine"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"41729","DOI":"10.1021\/acsami.5c07676","article-title":"Exosome-Functionalized Hydrogels Improve Cartilage Repair by Modulating BMSCs Migration and Differentiation","volume":"17","author":"Pei","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1021\/acsbiomaterials.5c00798","article-title":"Sustained and Localized Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles by an In Situ Forming Click PEG Hydrogel for Diabetic Nephropathy Therapy","volume":"11","author":"Bakhtiari","year":"2025","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1778883","DOI":"10.1080\/20013078.2020.1778883","article-title":"miR-23a-3p-abundant small extracellular vesicles released from Gelma\/nanoclay hydrogel for cartilage regeneration","volume":"9","author":"Hu","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_154","first-page":"1113","article-title":"Chitosan hydrogel incorporated with dental pulp stem cell-derived exosomes alleviates periodontitis in mice via a macrophage-dependent mechanism","volume":"5","author":"Shen","year":"2020","journal-title":"Bioact. Mater."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jconrel.2024.08.050","article-title":"Chondroitin sulfate-based microneedles for transdermal delivery of stem cell-derived extracellular vesicles to treat rheumatoid arthritis","volume":"375","author":"Bui","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"101058","DOI":"10.1016\/j.reth.2025.101058","article-title":"Mesenchymal stromal cell-derived extracellular vesicles in regenerative medicine: Standardisation, bioengineering and clinical translation","volume":"31","author":"Shimizu","year":"2026","journal-title":"Regen. Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41413-026-00549-x","article-title":"Advances in heterogeneity and classification of osteoarthritis","volume":"14","author":"Huang","year":"2026","journal-title":"Bone Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8208\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:00:10Z","timestamp":1789473610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":157,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188208"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188208","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}