[1]李泾,李尚佳,张昱韬,等.干细胞来源的外泌体在膝骨关节炎治疗中的研究进展[J].中国中医骨伤科杂志,2026,34(08):86-93.[doi:10.20085/j.cnki.issn1005-0205.260812]
 LI Jing,LI Shangjia,ZHANG Yutao,et al.Research Progress of Stem Cell-Derived Exosomes in the Treatment of Knee Osteoarthritis[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2026,34(08):86-93.[doi:10.20085/j.cnki.issn1005-0205.260812]
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干细胞来源的外泌体在膝骨关节炎治疗中的研究进展()

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第34卷
期数:
2026年08期
页码:
86-93
栏目:
文献综述
出版日期:
2026-08-10

文章信息/Info

Title:
Research Progress of Stem Cell-Derived Exosomes in the Treatment of Knee Osteoarthritis
文章编号:
1005-0205(2026)08-0086-08
作者:
李泾1李尚佳2张昱韬2张昊翔2袁普卫1△
1陕西中医药大学中西医结合学院(陕西 咸阳,712046)
2陕西中医药大学附属医院
Author(s):
LI Jing1LI Shangjia2ZHANG Yutao2ZHANG Haoxiang2YUAN Puwei1△
1School of Integrative Chinese and Western Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi China; 2Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi China.
关键词:
膝骨关节炎 干细胞来源外泌体 软骨修复 抗炎 临床转化
Keywords:
knee osteoarthritis stem cell-derived exosomes cartilage repair anti-inflammatory clinical translation
分类号:
R684.3
DOI:
10.20085/j.cnki.issn1005-0205.260812
文献标志码:
A
摘要:
膝骨关节炎以关节软骨退变、滑膜炎症、软骨下骨重塑及疼痛为核心病理特征,现有治疗手段难以逆转其退行性进程。干细胞来源外泌体是携带miRNA、蛋白质及生长因子等生物活性成分的纳米级囊泡,可通过介导细胞间信号传递参与膝骨关节炎干预,是当前值得关注的无细胞治疗方向。外泌体可通过抗炎、促进软骨修复及维持细胞外基质稳态等多重机制参与膝骨关节炎干预。总结不同来源干细胞外泌体的功能差异,并归纳体外细胞实验与动物模型的机制验证结果,旨在总结其在膝骨关节炎治疗中的基础研究依据与早期临床转化现状,为后续临床试验设计、疗效评价及标准化研究提供参考。当前仍存在核心成分调控网络不清晰、制备与评价标准缺失等问题,未来研究仍需围绕关键成分筛选、作用机制解析及技术标准化持续推进,以促进膝骨关节炎外泌体治疗的规范化研究与临床转化。
Abstract:
Knee osteoarthritis(KOA)is a joint disorder characterized by articular cartilage degeneration,synovial inflammation,subchondral bone remodeling,and pain as its core pathological manifestations.Current therapeutic strategies remain limited in their capacity to reverse its degenerative progression.Stem cell-derived exosomes are nanoscale vesicles that carry bioactive components such as microRNAs(miRNAs),proteins,and growth factors.By mediating intercellular communication,they participate in KOA intervention and have emerged as a promising cell-free therapeutic approach.Exosomes may exert therapeutic effects on KOA through multiple mechanisms,including anti-inflammatory activity,promotion of cartilage repair,and maintenance of extracellular matrix homeostasis.This review summarizes the functional differences among exosomes derived from various stem cell sources and integrates mechanistic evidence from in vitro cellular experiments and animal models.Its aim is to outline the foundational research basis and current status of early clinical translation of exosome-based therapy for KOA,thereby providing a reference for future clinical trial design,efficacy evaluation,and standardization research.However,important challenges remain,including the incomplete understanding of the regulatory networks of key functional components and the lack of standardized preparation and evaluation criteria.Future studies should continue to focus on identifying critical bioactive components,elucidating underlying mechanisms,and standardizing technologies—to advance both rigorous,standardized research and clinical transformation of exosome—based therapy for KOA.

参考文献/References:

[1] WU X H,LI S K,WU M M.Advances in electroacupuncture for treatment of knee osteoarthritis:mechanisms,efficacy,and future directions[J].Journal of Pain Research,2025,18:5083-5108.
[2] SHUMNALIEVA R,KOTOV G,MONOV S.Obesity-related knee osteoarthritis-current concepts[J].Life,2023,13(8):1650.
[3] ADOUNI M,AYDELIK H,FAISAL T R,et al.The effect of body weight on the knee joint biomechanics based on subject-specific finite element-musculoskeletal approach[J].Scientific Reports,2024,14:13777.
[4] ZHOU G H,ZHANG X Q,GU Z X,et al.Research progress in single-herb Chinese medicine and compound medicine for knee osteoarthritis[J].Combinatorial Chemistry & High Throughput Screening,2024,27(15):2180-2186.
[5] KREUTZINGER V,ZIEGELER K,LUITJENS J,et al.Limited effects of non-steroidal anti-inflammatory drugs(NSAIDs)on imaging outcomes in osteoarthritis:observational data from the osteoarthritis initiative(OAI)[J].BMC Musculoskeletal Disorders,2025,26(1):939.
[6] OKA T,SUZUKI K,TANAKA K,et al.Effectiveness of combined regenerative medicine and exercise therapy for patients with knee osteoarthritis:a scoping review[J].Frontiers in Rehabilitation Sciences,2025,6:1612615.
[7] XU K S,LI X,YAN M Y,et al.Simultaneous bilateral and staged total knee arthroplasty combined with unicompartmental knee arthroplasty in the treatment of bilateral knee osteoarthritis:comparison of early clinical outcomes,complications,and prosthesis survival[J].Journal of Orthopaedic Surgery and Research,2024,19(1):661.
[8] XUE H Y,SHEN X L,WANG Z H,et al.Research progress on mesenchymal stem cell-derived exosomes in the treatment of osteoporosis induced by knee osteoarthritis(Review)[J].International Journal of Molecular Medicine,2025,56(4):160.
[9] BUFORD D.Mesenchymal stem cell exosomes for the treatment of knee osteoarthritis current clinical status and future potential[J].Clinics in Sports Medicine,2025,44(4):721-733.
[10] WANG C J,YAO B W.Efficacy and safety of platelet-rich plasma injections for the treatment of knee osteoarthritis:a systematic review and meta-analysis of randomized controlled trials[J].European Journal of Medical Research,2025,30(1):992.
[11] JIANG W,CHEN H X,LIN Y,et al.Mechanical stress abnormalities promote chondrocyte senescence:the pathogenesis of knee osteoarthritis[J].Biomedicine & Pharmacotherapy,2023,167:115552.
[12] SHI J M,DU G H.Metabolic reprogramming of glycolysis favors cartilage progenitor cells rejuvenation[J].Joint Bone Spine,2024,91(2):105634.
[13] HU W H,CHEN Y Q,DOU C,et al.Microenvironment in subchondral bone:predominant regulator for the treatment of osteoarthritis[J].Annals of the Rheumatic Diseases,2021,80(4):413-422.
[14] WANG Y X,XU J H,ZHAO Z D,et al.Dickkopf-3 enhances the chondroprotective effect of chondrogenic progenitor cells in a rat model of posttraumatic osteoarthritis[J].Journal of Orthopaedic Surgery and Research,2025,20(1):1032.
[15] DANG Y F,LIU Y H,ZHANG B J,et al.Aging microenvironment in osteoarthritis focusing on early-stage alterations and targeted therapies[J].Bone Research,2025,13:84.
[16] TANG H,GONG X S,DAI J J,et al.The IRF1/GBP5 axis promotes osteoarthritis progression by activating chondrocyte pyroptosis[J].Journal of Orthopaedic Translation,2024,44:47-59.
[17] DA COSTA B R,PEREIRA T V,SAADAT P,et al.Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis:network meta-analysis[J].BMJ,2021,375:n2321.
[18] LATOURTE A,RAT A C,OMOROU A,et al.Do glucocorticoid injections increase the risk of knee osteoarthritis progression over 5 years?[J].Arthritis & Rheumatology,2022,74(8):1343-1351.
[19] KNAPIK M,(·overZ)ELAZO D A,OSOWIECKA K,et al.Efficacy of anti-interleukin-1 therapeutics in the treatment of knee osteoarthritis:a systematic review and meta-analysis of randomized controlled trials from the years 2000 to 2023[J].Journal of Clinical Medicine,2024,13(10):2859.
[20] DENG M C,HU Y,ZHANG Z Z,et al.Unicondylar knee replacement versus total knee replacement for the treatment of medial knee osteoarthritis:a systematic review and meta-analysis[J].Archives of Orthopaedic and Trauma Surgery,2021,141(8):1361-1372.
[21] BIRMINGHAM T B,PRIMEAU C A,SHARIFF S Z,et al.Incidence of total knee arthroplasty after arthroscopic surgery for knee osteoarthritis:a secondary analysis of a randomized clinical trial[J].JAMA Network Open,2024,7(4):e246578.
[22] ARYA S B,COLLIE S P,PARENT C A.The ins-and-outs of exosome biogenesis,secretion,and internalization[J].Trends in Cell Biology,2024,34(2):90-108.
[23] WU T Y,ZHU W W,DUAN R,et al.Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p[J].Journal of Nanobiotechnology,2024,22(1):666.
[24] ZHANG Y,LIU Q Q,ZHANG X M,et al.Recent advances in exosome-mediated nucleic acid delivery for cancer therapy[J].Journal of Nanobiotechnology,2022,20(1):279.
[25] LONGO A,MANGANELLI V,MISASI R,et al.Extracellular vesicles in the crosstalk of autophagy and apoptosis:a role for lipid rafts[J].Cells,2025,14(10):749.
[26] XU F,LUO S M,LU P P,et al.Composition,functions,and applications of exosomal membrane proteins[J].Frontiers in Immunology,2024,15:1408415.
[27] SU Y C,DU F,LIU J X.Unpacking the role of exosomal proteins and nucleic acids in ischemic stroke:insights from diverse cellular sources[J].International Journal of Biological Macromolecules,2025,322:147081.
[28] SWARN S,ALASEEM A M,SHARMA S,et al.Gossypol-based nanocarriers for cancer treatment:advances and future perspectives[J].Journal of Biomaterials Science:Polymer Edition,2026,37(7):1384-1415.
[29] TANG R T,JUAN Z Q,XING F T,et al.Exosome-mediated crosstalk between immune cells and tumor microenvironment in lung cancer:implications for immune evasion and therapeutic resistance[J].Cellular Signalling,2026,142:112452.
[30] WANG C,LI Z L,LIU Y N,et al.Exosomes in atherosclerosis:performers,bystanders,biomarkers,and therapeutic targets[J].Theranostics,2021,11(8):3996-4010.
[31] WU J Y,WU J H,XIANG W,et al.Engineering exosomes derived from TNF-α preconditioned IPFP-MSCs enhance both yield and therapeutic efficacy for osteoarthritis[J].Journal of Nanobiotechnology,2024,22(1):555.
[32] BLACKLER G,YUE L Z,KLAPAK J,et al.Targeting STAT6-mediated synovial macrophage activation improves pain in experimental knee osteoarthritis[J].Arthritis Research & Therapy,2024,26(1):73.
[33] SUN H,HU S,ZHANG Z J,et al.Expression of exosomal microRNAs during chondrogenic differentiation of human bone mesenchymal stem cells[J].Journal of Cellular Biochemistry,2024,125(6):e30559.
[34] DONG X Y,SUN L,HU D,et al.Construction of curcumin-loaded mesenchymal stem cell-derived exosomes and their mechanism in inhibiting pyroptosis during hepatic ischemia-reperfusion injury[J].Pharmaceuticals,2026,19(2):296.
[35] QIAO X,TANG J,DOU L,et al.Dental pulp stem cell-derived exosomes regulate anti-inflammatory and osteogenesis in periodontal ligament stem cells and promote the repair of experimental periodontitis in rats[J].International Journal of Nanomedicine,2023,18:4683-4703.
[36] LI J H,XU J,HUANG C,et al.Houttuynia cordata-derived exosome-like nanoparticles mitigate colitis in mice via inhibition of the NLRP3 signaling pathway and modulation of the gut microbiota[J].International Journal of Nanomedicine,2024,19:13991-14018.
[37] SAMPATH S J P,RATH S N,KOTIKALAPUDI N,et al.Beneficial effects of secretome derived from mesenchymal stem cells with stigmasterol to negate IL-1β-induced inflammation in-vitro using rat chondrocytes-OA management[J].Inflammopharmacology,2021,29(6):1701-1717.
[38] WANG L M,CHEN J,SONG J,et al.Activation of the Wnt/β-catenin signalling pathway enhances exosome production by hucMSCs and improves their capability to promote diabetic wound healing[J].Journal of Nanobiotechnology,2024,22(1):373.
[39] LI W Z,MAO M Z,TAO C,et al.Wogonin pretreatment of infrapatellar fat pad mesenchymal stem cell-derived exosomes advances articular cartilage repair in osteoarthritis[J].Bone & Joint Research,2025,14(12):1064-1079.
[40] JIN Y,XU M,ZHU H,et al.Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis[J].Journal of Cellular and Molecular Medicine,2021,25(19):9281-9294.
[41] CHANG L H,WU S C,CHEN C H,et al.Exosomes derived from hypoxia-cultured human adipose stem cells alleviate articular chondrocyte inflammaging and post-traumatic osteoarthritis progression[J].International Journal of Molecular Sciences,2023,24(17):13414.
[42] YANG J Y,CHEN Z Y,PAN D Y,et al.Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration[J].International Journal of Nanomedicine,2020,15:5911-5926.
[43] SUN W X,QU S Z,JI M X,et al.BMP-7 modified exosomes derived from synovial mesenchymal stem cells attenuate osteoarthritis by M2 polarization of macrophages[J].Heliyon,2023,9(9):e19934.
[44] FU Y,CUI S J,ZHOU Y H,et al.Dental pulp stem cell-derived exosomes alleviate mice knee osteoarthritis by inhibiting TRPV4-mediated osteoclast activation[J].International Journal of Molecular Sciences,2023,24(5):4926.
[45] HE L,HE T W,XING J H,et al.Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis[J].Stem Cell Research & Therapy,2020,11(1):276.
[46] MATHEW B,TORRES L A,ACHA L G,et al.Uptake and distribution of administered bone marrow mesenchymal stem cell extracellular vesicles in retina[J].Cells,2021,10(4):730.
[47] YU M C,WANG D,CHEN X,et al.BMSCs-derived mitochondria improve osteoarthritis by ameliorating mitochondrial dysfunction and promoting mitochondrial biogenesis in chondrocytes[J].Stem Cell Reviews and Reports,2022,18(8):3092-3111.
[48] KANG J F,JIE L S,FU H Y,et al.Adipose mesenchymal stem cells derived exosomes ameliorates KOA cartilage damage and inflammation by activation of PINK1-mediated mitochondrial autophagy[J].FASEB Journal,2025,39(14):e70811.
[49] ZHANG H Y,LIN C X,ZENG C,et al.Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2[J].Annals of the Rheumatic Diseases,2018,77(10):1524-1534.
[50] YOSHIDA S,NISHITANI K,YOSHITOMI H,et al.Knee alignment correction by high tibial osteotomy reduces symptoms and synovial inflammation in knee osteoarthritis accompanied by macrophage phenotypic change from M1 to M2[J].Arthritis & Rheumatology,2023,75(6):950-960.
[51] JANCZI T,BÖHM B,FEHRL Y,et al.Mechanical forces trigger invasive behavior in synovial fibroblasts through N-cadherin/ADAM15-dependent modulation of LncRNA H19[J].Scientific Reports,2025,15:9814.
[52] CHEN K T,HUANG C C,YADAV V K,et al.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[J].International Journal of Pharmaceutics,2026,687:126367.
[53] LI R,LI D Z,WANG H N,et al.Exosomes from adipose-derived stem cells regulate M1/M2 macrophage phenotypic polarization to promote bone healing via miR-451a/MIF[J].Stem Cell Research & Therapy,2022,13(1):149.
[54] LI Z Y,LI Q X,TONG K,et al.BMSC-derived exosomes promote tendon-bone healing after anterior cruciate ligament reconstruction by regulating M1/M2 macrophage polarization in rats[J].Stem Cell Research & Therapy,2022,13(1):295.
[55] SAJADI S,KHADEMBASHIRI M A,RAISSI G,et al.The role of adipose-derived stem cells in knee osteoarthritis treatment:insights from a triple-blind clinical study[J].Stem Cell Research & Therapy,2025,16(1):242.
[56] OLIVAS C G,SHAULY O,HUTCHISON D M,et al.Harnessing regenerative science in aesthetic surgery:the biologically driven future[J].Journal of Clinical Medicine,2025,14(17):6205.
[57] ZHENG M L,HONG X T,LIAO P H,et al.Plant-derived exosome-like nanoparticles:a promising therapeutic for neurological disorders and drug delivery[J].International Journal of Nanomedicine,2025,20:15769-15791.
[58] DU B,ZOU Q Q,WANG X,et al.Multi-targeted engineered hybrid exosomes as Aβ nanoscavengers and inflammatory modulators for multi-pathway intervention in Alzheimer's disease[J].Biomaterials,2025,322:123403.
[59] EBERLE A B,VISA N.Quality control of mRNP biogenesis:networking at the transcription site[J].Seminars in Cell & Developmental Biology,2014,32:37-46.
[60] CASADO J G,BLÁZQUEZ R,VELA F J,et al.Mesenchymal stem cell-derived exosomes:immunomodulatory evaluation in an antigen-induced synovitis porcine model[J].Frontiers in Veterinary Science,2017,4:39.
[61] WANG Y,JIANG H,CHEN Q,et al.Myofibroblast-targeting extracellular vesicles:a promising platform for cardiac fibrosis drug delivery[J].Biomaterials Research,2025,29:0179.
[62] WANG Y Z,KONG Y J,DU J J,et al.Injection of human umbilical cord mesenchymal stem cells exosomes for the treatment of knee osteoarthritis:from preclinical to clinical research[J].Journal of Translational Medicine,2025,23(1):641.
(收稿日期:2026-01-05)

备注/Memo

备注/Memo:
基金项目:国家自然科学基金项目(82474348)
国家中医药管理局2018年全国名老中医药专家传承工作室建设项目(国中医药人教函〔2018〕134号)
陕西省中医药管理局第二批中医药重点研究室建设项目(陕中医药发〔2018〕32号)
陕西中医药大学学科建设创新团队项目(2019YL-02)
长安医学关中李氏骨伤学术流派传承工作室建设项目(陕中医药发〔2018〕40号)
陕西省骨退行性疾病中西医结合防治重点研究室建设项目(陕中医药发〔2018〕32号)
陕西省教育厅科研项目(陕教函〔2025〕96号)
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更新日期/Last Update: 2026-08-15