切换至 "中华医学电子期刊资源库"

中华关节外科杂志(电子版) ›› 2022, Vol. 16 ›› Issue (04) : 472 -476. doi: 10.3877/cma.j.issn.1674-134X.2022.04.014

综述

间充质干细胞来源细胞外囊泡治疗膝骨关节炎的研究进展
马明1, 贾更新1, 刘小龙1, 耿彬2, 夏亚一2,()   
  1. 1. 730000 兰州大学第二临床医学院
    2. 730000 兰州大学第二医院骨科
  • 收稿日期:2021-07-09 出版日期:2022-08-01
  • 通信作者: 夏亚一
  • 基金资助:
    国家自然科学科学基金(81960403,81874017); 甘肃省自然科学基金(20JR5RA320)

Progress of mesenchymal stem cell-derived extracellular vesicles in treatment of knee osteoarthritis

Ming Ma1, Gengxin Jia1, Xiaolong Liu1, Bin Geng2, Yayi Xia2,()   

  1. 1. Second Clinical Medical School, Lanzhou University, Lanzhou 730000, China
    2. Department of Orthopaedics, Gansu Key Laboratory of Orthopaedics, Lanzhou University Second Hospital, Lanzhou 730000, China
  • Received:2021-07-09 Published:2022-08-01
  • Corresponding author: Yayi Xia
引用本文:

马明, 贾更新, 刘小龙, 耿彬, 夏亚一. 间充质干细胞来源细胞外囊泡治疗膝骨关节炎的研究进展[J]. 中华关节外科杂志(电子版), 2022, 16(04): 472-476.

Ming Ma, Gengxin Jia, Xiaolong Liu, Bin Geng, Yayi Xia. Progress of mesenchymal stem cell-derived extracellular vesicles in treatment of knee osteoarthritis[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2022, 16(04): 472-476.

膝骨关节炎(KOA)是一种老年人常见的关节慢性退行性变,与关节软骨的退化和软骨下骨的重塑相关。现阶段,KOA的治疗以阶梯治疗为主,即非手术基础治疗、药物治疗、修复性治疗和重建治疗。间充质干细胞(MSCs)因其巨大的增殖潜力,被广泛用于多种疾病的治疗,这其中就包括KOA。MSCs来源的细胞外囊泡(EVs)通过促进关节软骨的再生,成为治疗KOA非常有潜力的方法。本文通过对EVs的产生机制和制备方法、EVs在治疗KOA中的应用、EVs治疗KOA的有效性和安全性以及未来EVs治疗KOA的展望进行论述,为EVs治疗KOA提供可行的理论支持。

Knee osteoarthritis (KOA) is a chronic degenerative joint degeneration commonly seen in the elderly and is associated with articular cartilage degeneration and subchondral bone remodeling. At present, the treatment of KOA is based on step therapy, including non-surgical primary treatment, pharmacological treatment, restorative treatment, and reconstructive treatment. Mesenchymal stem cells (MSCs) are widely used to treat many diseases, including KOA, because of the great proliferative potential. Extracellular vesicles (EVs) are a promising treatment for KOA by promoting the regeneration of articular cartilage. This review provided feasible theoretical supports for the treatment of KOA with EVs by discussing the mechanism of generation and preparation of EVs, the application of EVs in the treatment of KOA, the efficacy and safety of EVs in the treatment of KOA, and the future outlook of EVs in the treatment of KOA.

表1 EVs的不同分离方式及其优缺点总结
表2 EVs治疗KOA的机制总结
表3 EVs治疗KOA的有效性和安全性动物在体实验
[1]
Buckwalter JA, Mankin HJ, Grodzinsky AJ. Articular cartilage and osteoarthritis[J]. Instr Course Lect, 2005, 54: 465-480.
[2]
Sanchez C, Pesesse L, Gabay O, et al. Regulation of subchondral bone osteoblast metabolism by cyclic compression[J]. Arthritis Rheum, 2012, 64(4): 1193-1203.
[3]
Tang X, Wang SF, Zhan SY, et al. The prevalence of symptomatic knee osteoarthritis in China results from the China health and retirement longitudinal study[J]. Arthritis Rheumatol, 2016, 68(3): 648-653.
[4]
Chen H, Wu J, Wang Z, et al. Trends and patterns of knee osteoarthritis in China: a longitudinal study of 17.7 million adults from 2008 to 2017[J]. Int J Environ Res Public Health, 2021, 18(16): 8864.
[5]
王波,余楠生.膝骨关节炎阶梯治疗专家共识(2018年版)[J/CD].中华关节外科杂志(电子版)201913(1):124-130.
[6]
中华医学会骨科学分会关节外科学组,中国医师协会骨科医师分会骨关节炎学组,国家老年疾病临床医学研究中心,中华骨科杂志编辑部.中国骨关节炎诊疗指南(2021年版)[J].中华骨科杂志202141(18): 1291-1314.
[7]
Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American college of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee[J]. Arthritis Care Res (Hoboken), 2020, 72(2): 220-233.
[8]
Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis[J]. Osteoarthritis Cartilage, 2019, 27(11): 1578-1589.
[9]
张虎,冯志军,韩纲.肿瘤型人工膝关节置换术后假体并发症的临床研究[J/CD].中华关节外科杂志(电子版)202115(1):12-17.
[10]
Gowen A, Shahjin F, Chand S, et al. Mesenchymal stem Cell-Derived extracellular vesicles: challenges in clinical applications[J/OL]. Front Cell Dev Biol, 2020, 8: 149. DOI:10.3389/fcell.2020.00149
[11]
Toma C, Wagner WR, Bowry S, et al. Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics[J]. Circ Res, 2009, 104(3): 398-402.
[12]
Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends[J]. J Cell Biol, 2013, 200(4): 373-383.
[13]
Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles[J]. Annu Rev Cell Dev Biol, 2014, 30: 255-289.
[14]
Tauro BJ, Greening DW, Mathias RA, et al. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes[J]. Methods, 2012, 56(2): 293-304.
[15]
Yang F, Liao X, Tian Y, et al. Exosome separation using microfluidic systems: size-based, immunoaffinity-based and dynamic methodologies[J/OL]. Biotechnol J, 2017, 12(4). DOI: 10.1002/biot.201600699.
[16]
Batrakova EV, Kim MS. Using exosomes, naturally-equipped nanocarriers, for drug delivery[J]. J Control Release, 2015, 219: 396-405.
[17]
Lozano-Ramos I, Bancu I, Oliveira-Tercero A, et al. Size-exclusion chromatography-based enrichment of extracellular vesicles from urine samples[J/OL]. J Extracell Vesicles, 2015, 4: 27369. DOI: 10.3402/jev.v4.27369.
[18]
Momen-Heravi F, Balaj L, Alian S, et al. Impact of biofluid viscosity on size and sedimentation efficiency of the isolated microvesicles[J/OL]. Front Physiol, 2012, 3: 162. DOI: 10.3389/fphys.2012.00162.
[19]
Zhang H, Lyden D. Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization[J]. Nat Protoc, 2019, 14(4): 1027-1053.
[20]
Furuta T, Miyaki S, Ishitobi H, et al. Mesenchymal stem Cell-Derived exosomes promote fracture healing in a mouse model[J]. Stem Cells Transl Med, 2016, 5(12): 1620-1630.
[21]
Kolhe R, Hunter M, Liu S, et al. Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis[J/OL]. Sci Rep, 2017, 7(1): 2029. DOI: 10.1038/s41598-017-01905-y.
[22]
Hu H, Dong L, Bu Z, et al. miR-23a-3p-abundant small extracellular vesicles released from gelma/nanoclay hydrogel for cartilage regeneration[J/OL]. J Extracell Vesicles, 2020, 9(1): 1778883. DOI: 10.1080/20013078.2020.1778883.
[23]
Ham O, Song BW, Lee SY, et al. The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling[J]. Biomaterials, 2012, 33(18): 4500-4507.
[24]
Wang R, Xu B, Xu H. TGF-β1 promoted chondrocyte proliferation by regulating Sp1 through MSC-exosomes derived miR-135b[J]. Cell Cycle, 2018, 17(24): 2756-2765.
[25]
Mao G, Zhang Z, Hu S, et al. Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A[J]. Stem Cell Res Ther, 2018, 9(1): 247.
[26]
He L, Chen Y, Ke Z, et al. Exosomes derived from miRNA-210 overexpressing bone marrow mesenchymal stem cells protect lipopolysaccharide induced chondrocytes injury via the NF-κB pathway[J/OL]. Gene, 2020, 751: 144764. DOI: 10.1016/j.gene.2020.144764.
[27]
Mao G, Xu Y, Long D, et al. Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis[J/OL]. Stem Cell Res Ther, 2021, 12(1): 389. DOI: 10.1186/s13287-021-02431-5
[28]
Wu X, Crawford R, Xiao Y, et al. Osteoarthritic subchondral bone release exosomes that promote cartilage degeneration[J/OL]. Cells, 2021, 10(2): 251. DOI: 10.3390/cells10020251
[29]
Zhang S, Chu WC, Lai RC, et al. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration[J]. Osteoarthritis Cartilage, 2016, 24(12): 2135-2140.
[30]
Qiu M, Liu D, Fu Q. MiR-129-5p shuttled by human synovial mesenchymal stem cell-derived exosomes relieves IL-1β induced osteoarthritis via targeting HMGB1[J/OL]. Life Sci, 2021, 269: 118987. DOI: 10.1016/j.lfs.2020.118987
[31]
Kato T, Miyaki S, Ishitobi H, et al. Exosomes from IL-1β stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes[J/OL]. Arthritis Res Ther, 2014, 16(4): R163. DOI: 10.1186/ar4679.
[32]
Gao K, Zhu W, Li H, et al. Association between cytokines and exosomes in synovial fluid of individuals with knee osteoarthritis[J]. Mod Rheumatol, 2020, 30(4): 758-764.
[33]
Wang Y, Yu D, Liu Z, et al. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix[J/OL]. Stem Cell Res Ther, 2017, 8(1): 189. DOI: 10.1186/s13287-017-0632-0.
[34]
Cosenza S, Ruiz M, Toupet K, et al. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis[J/OL]. Sci Rep, 2017, 7(1): 16214. DOI: 10.1038/s41598-017-15376-8.
[35]
Tao SC, Yuan T, Zhang YL, et al. 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[J]. Theranostics, 2017, 7(1): 180-195.
[36]
Liu XC, Wang LB, Ma CS, et al. Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway[J/OL]. J Orthop Surg Res, 2019, 14(1): 470. DOI: 10.1186/s13018-019-1529-7.
[37]
Duan A, Shen K, Li B, et al. 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[J/OL]. Stem Cell Res Ther, 2021, 12(1): 427. DOI: 10.1186/s13287-021-02507-2.
[38]
Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines[J/OL]. J Extracell Vesicles, 2018, 7(1): 1535750. DOI: 10.1080/20013078.2018.1535750.
[39]
Lener T, Gimona M, Aigner L, et al. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper[J/OL]. J Extracell Vesicles, 2015, 4: 30087. DOI: 10.3402/jev.v4.30087.
[40]
Huyan T, Li H, Peng H, et al. Extracellular vesicles - advanced nanocarriers in cancer therapy: progress and achievements[J/OL]. Int J Nanomedicine, 2020, 15: 6485-6502. DOI: 0.2147/IJN.S238099.
[41]
Yao X, Lyu P, Yoo K, et al. Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing[J/OL]. J Extracell Vesicles, 2021, 10(5): e12076. DOI: 10.1002/jev2.12076.
[42]
Li W, Liu Y, Zhang P, et al. Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration[J]. ACS Appl Mater Interfaces, 2018, 10(6): 5240-5254.
[43]
Zhang K, Zhao X, Chen X, et al. Enhanced therapeutic effects of mesenchymal stem Cell-Derived exosomes with an injectable hydrogel for hindlimb ischemia treatment[J]. ACS Appl Mater Interfaces, 2018, 10(36): 30081-30091.
[1] 闫文, 谢兴文, 顾玉彪, 雷宁波, 马成, 于文霞, 高亚雄, 张磊. 微小RNA与全膝关节置换术后深静脉血栓的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(06): 842-846.
[2] 樊绪国, 赵永刚, 杨砚伟. 腓骨在膝骨关节炎作用的研究观点[J]. 中华关节外科杂志(电子版), 2023, 17(06): 855-859.
[3] 李善武, 叶永杰, 王兵, 王子呓, 银毅, 孙官军, 张大刚. 胫骨高位截骨与单髁置换的早期疗效比较[J]. 中华关节外科杂志(电子版), 2023, 17(06): 882-888.
[4] 张中斌, 付琨朋, 朱凯, 张玉, 李华. 胫骨高位截骨术与富血小板血浆治疗膝骨关节炎的疗效[J]. 中华关节外科杂志(电子版), 2023, 17(05): 633-641.
[5] 陈宏兴, 张立军, 张勇, 李虎, 周驰, 凡一诺. 膝骨关节炎关节镜清理术后中药外用疗效的Meta分析[J]. 中华关节外科杂志(电子版), 2023, 17(05): 663-672.
[6] 王岩, 马剑雄, 郎爽, 董本超, 田爱现, 李岩, 孙磊, 靳洪震, 卢斌, 王颖, 柏豪豪, 马信龙. 外泌体在骨质疏松症诊疗中应用的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 673-678.
[7] 赵之栋, 李众利. 骨关节炎早期诊治的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 689-693.
[8] 刘伦, 王云鹭, 李锡勇, 韩鹏飞, 张鹏, 李晓东. 机器人辅助膝关节单髁置换术的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 715-721.
[9] 胡银华, 薛龙. 中国中老年人症状性膝骨关节炎的发病率及危险因素[J]. 中华关节外科杂志(电子版), 2023, 17(04): 470-478.
[10] 代雯荣, 赵丽娟, 李智慧. 细胞外囊泡对胚胎着床影响的研究进展[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 616-620.
[11] 王邦郁, 陈晓鹏, 唐国军, 王佳妮. 尿液细胞外囊泡circRNA分类器对高级别前列腺癌诊断价值的初步研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 339-342.
[12] 王旭, 师绍敏, 毛燕, 季上, 刘亚玲. 肝酶代谢与骨关节炎相关性的研究进展[J]. 中华老年骨科与康复电子杂志, 2023, 09(06): 379-384.
[13] 周晓强, 孙超, 虞宵, 金宇杰, 李志强, 张向鑫, 陈广祥. 同一患者同期行全膝和单髁置换术的早期临床疗效[J]. 中华老年骨科与康复电子杂志, 2023, 09(05): 275-281.
[14] 马聪, 李雪靖, 郑晓佐, 张晓阳, 段坤峰, 刘国强, 郄素会. 关节腔内注射富血小板血浆与透明质酸钠治疗Ⅰ-Ⅲ期膝骨关节炎的对比研究[J]. 中华老年骨科与康复电子杂志, 2023, 09(05): 282-288.
[15] 郭芳芳, 李珉珉. 狼疮肾炎无创生物标志物的研究进展[J]. 中华诊断学电子杂志, 2023, 11(04): 271-275.
阅读次数
全文


摘要