Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects

被引：222
作者：
Xia, Chen [1 ,2 ,3 ]
Zeng, Zhongyou [1 ,4 ]
Fang, Bin [1 ,5 ]
Tao, Min [1 ,2 ]
Gu, Chenhui [1 ,2 ]
Zheng, Lin [1 ,2 ]
Wang, Yiyun [1 ,2 ]
Shi, Yiling [1 ,2 ]
Fang, Chen [1 ,2 ]
Mei, Sheng [1 ,2 ]
Chen, Qi [3 ]
Zhao, Juanjuan [6 ]
Lin, Xianfeng [1 ,2 ]
Fan, Shunwu [1 ,2 ]
Jin, Yongming [3 ]
Chen, Pengfei [1 ,2 ]
机构：
[1] Zhejiang Univ, Dept Orthopaed Surg, Sir Run Run Shaw Hosp, Coll Med, Hangzhou, Zhejiang, Peoples R China
[2] Key Lab Musculoskeletal Syst Degenerat & Regenera, Hangzhou, Zhejiang, Peoples R China
[3] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Peoples Hosp, Hangzhou, Zhejiang, Peoples R China
[4] Armed Police Forces, Jiaxing Hosp Zhejiang Gen Corps, Dept Orthoped 2, Jiaxing, Peoples R China
[5] Shaoxing Cent Hosp, Dept Orthopaed, Shaoxing, Peoples R China
[6] Zhejiang Univ, Dept Cardiol, Biomed Res Therapy Ctr, Sir Run Run Shaw Hosp,Med Coll, Hangzhou, Zhejiang, Peoples R China
来源：
FREE RADICAL BIOLOGY AND MEDICINE | 2019年 / 143卷
基金：
国家重点研发计划; 中国国家自然科学基金;
关键词：
Exosome; Mitochondrion; NLRP3; inflammasome; Intervertebral disc degeneration; LOW-BACK-PAIN; HUMAN NUCLEUS PULPOSUS; EXTRACELLULAR VESICLES; INFORMATION-TRANSFER; LUMBAR FUSION; ACTIVATION; INFLAMMASOME; MITOCHONDRIA; EXPRESSION; SURGERY;
D O I：
10.1016/j.freeradbiomed.2019.07.026
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutics. We first manufactured and evaluated the characteristics of exosomes. Then, we investigated the effects of exosomes on H2O2-induced nucleus pulposus (NP) cell inflammation. Third, we tested the function of exosomes with respect to H2O2-induced ROS production and mitochondrial dysfunction. Finally, the therapeutic effect of exosomes on IVDD was investigated using a rabbit IVDD model. Results showed that exosomes play an anti-inflammatory role in pathological NP cells by suppressing inflammatory mediators and NLRP3 inflammasome activation. Moreover, it was suggested that exosomes might supply mitochondrial proteins to NP cells, and that the damaged mitochondria could be restored with this supplement. Further, in the rabbit IVDD model, exosomes significantly prevented the progression of degenerative changes. Our results confirmed that the NLRP3 inflammasome is an effective target for IVDD treatment and that the injection of exosomes could be a promising therapeutic strategy.
引用
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页码：1 / 15
页数：15
相关论文
共 55 条
  • [1] Could sudden increases in physical activity cause degeneration of intervertebral discs?
    Adams, MA
    Dolan, P
    [J]. LANCET, 1997, 350 (9079) : 734 - 735
  • [2] The clinical continuum of cryopyrinopathies -: Novel CIAS1 mutations in north American patients and a new cryopyrin model
    Aksentijevich, Ivona
    Putnam, Christopher D.
    Remmers, Elaine F.
    Mueller, James L.
    Le, Julie
    Kolodner, Richard D.
    Moak, Zachary
    Chuang, Michael
    Austin, Frances
    Goldbach-Mansky, Raphaela
    Hoffman, Hal M.
    Kastner, Daniel L.
    [J]. ARTHRITIS AND RHEUMATISM, 2007, 56 (04): : 1273 - 1285
  • [3] Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells
    Basit, Farhan
    van Oppen, Lisanne M. P. E.
    Schoeckel, Laura
    Bossenbroek, Hasse M.
    van Emst-de Vries, Sjenet E.
    Hermeling, Johannes C. W.
    Grefte, Sander
    Kopitz, Charlotte
    Heroult, Melanie
    Willems, Peter H. G. M.
    Koopman, Werner J. H.
    [J]. CELL DEATH & DISEASE, 2017, 8 : e2716 - e2716
  • [4] Mechanical low back pain-a rheumatologist's view
    Borenstein, David
    [J]. NATURE REVIEWS RHEUMATOLOGY, 2013, 9 (11) : 643 - 653
  • [5] Multiple Roles of Mitochondria in Aging Processes
    Cedikova, M.
    Pitule, P.
    Kripnerova, M.
    Markova, M.
    Kuncova, J.
    [J]. PHYSIOLOGICAL RESEARCH, 2016, 65 : S519 - S531
  • [6] Degenerative Magnetic Resonance Imaging Changes in Patients With Chronic Low Back Pain A Systematic Review
    Chou, Dean
    Samartzis, Dino
    Bellabarba, Carlo
    Patel, Alpesh
    Luk, Keith D. K.
    Kisser, Jeannette M. Schenk
    Skelly, Andrea C.
    [J]. SPINE, 2011, 36 (21) : S43 - S53
  • [7] Surgery for Low Back Pain A Review of the Evidence for an American Pain Society Clinical Practice Guideline
    Chou, Roger
    Baisden, Jamie
    Carragee, Eugene J.
    Resnick, Daniel K.
    Shaffer, William O.
    Loeser, John D.
    [J]. SPINE, 2009, 34 (10) : 1094 - 1109
  • [8] Material properties in unconfined compression of human nucleus pulposus, injectable hyaluronic acid-based hydrogels and tissue engineering scaffolds
    Cloyd, Jordan M.
    Malhotra, Neil R.
    Weng, Lihui
    Chen, Weiliam
    Mauck, Robert L.
    Elliott, Dawn M.
    [J]. EUROPEAN SPINE JOURNAL, 2007, 16 (11) : 1892 - 1898
  • [9] Ectosomes and exosomes: shedding the confusion between extracellular vesicles
    Cocucci, Emanuele
    Meldolesi, Jacopo
    [J]. TRENDS IN CELL BIOLOGY, 2015, 25 (06) : 364 - 372
  • [10] What Is the Source of Chronic Low Back Pain and Does Age Play a Role?
    DePalma, Michael J.
    Ketchum, Jessica M.
    Saullo, Thomas
    [J]. PAIN MEDICINE, 2011, 12 (02) : 224 - 233
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