Research progress of mesenchymal stem cell-derived exosomes in the repair of intervertebral disc degeneration

doi:10.3877/cma.j.issn.1673-9450.2021.02.012

Abstract

Abstract:

Mesenchymal stem cell-derived exosomes (MSC-Exos) are a kind of extracellular vesicles with a diameter of 30~100 nm, which carry nucleic acids, proteins, lipids and other bioactive substances. MSC-Exos play an important role in intercellular communication and material exchange. MSC-Exos can not only inhibit cell pyrolysis, cell oxidative stress and cell apoptosis, but also increase the synthesis of extracellular matrix (ECM) in vivo and in vitro studies, thereby can retard or even reverse intervertebral disc degeneration. This article reviews the research progress of MSC-Exos in the study of intervertebral disc degeneration to provide references for the treatment of intervertebral disc degeneration disease.

Key words: Mesenchymal stem cells, Exosomes, Intervertebral disk degeneration

Wenjie Zhao, Wenjie Zhang, Liang Zhang, Pengzhi Shi, Man Hu, Yu Zhang, Pingchuan Wang, Junwu Wang. Research progress of mesenchymal stem cell-derived exosomes in the repair of intervertebral disc degeneration[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2021, 16(02): 153-157.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhssyxfzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1673-9450.2021.02.012

https://zhssyxfzz.cma-cmc.com.cn/EN/Y2021/V16/I02/153

Figures/Tables 1

References 37

[1]	Hay SI, Jayaraman SP, Truelsen T, et al. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 [J]. Lancet, 2016, 388(10053): 1545-1602.
[2]	Urits I, Burshtein A, Sharma M, et al. Low back pain, a comprehensive review: pathophysiology, diagnosis, and treatment[J]. Curr Pain Headache Rep, 2019, 23(3): 23.
[3]	Grunhagen T, Shirazi-Adl A, Fairbank JC, et al. Intervertebral disk nutrition: a review of factors influencing concentrations of nutrients and metabolites[J]. Orthop Clin North Am, 2011, 42(4): 465-477.
[4]	Xie L, Chen Z, Liu M, et al. MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis[J]. Mol Mol Ther Nucleic Acids, 2020, 22: 601-614.
[5]	Pennicooke B, Moriguchi Y, Hussain I, et al. Biological treatment approaches for degenerative disc disease: a Review of clinical trials and future directions[J]. Cureus, 2016, 8(11): e892-e892.
[6]	Ural IH, Alptekin K, Ketenci A, et al. Fibroblast transplantation results to the degenerated rabbit lumbar intervertebraldiscs[J]. Open Orthop J, 2017, 11: 404-416.
[7]	Doench I, Torres-Ramos MEW, Montembault A, et al. Injectable and gellable chitosan formulations filled with cellulose nanofibers for intervertebral disc tissue engineering[J]. Polymers (Basel), 2018, 10(11): 1202.
[8]	Ren S, Liu Y, Ma J, et al. Treatment of rabbit intervertebral disc degeneration with co-transfection by adeno-associated virus-mediated SOX9 and osteogenic protein-1 double genes in vivo[J]. Int J Mol Med, 2013, 32(5): 1063-1068.
[9]	Chujo T, An HS, Akeda K, et al. Effects of growth differentiation factor-5 on the intervertebral disc - In vitro bovine study and in vivo rabbit disc degeneration model study[J]. Spine, 2006, 31(25): 2909-2917.
[10]	Gruber HE, Ingram JA, Norton HJ, et al. Senescence in cells of the aging and degenerating intervertebral disc - Immunolocalization of senescence-associated beta-galactosidase in human and sand rat discs[J]. Spine, 2007, 32(3): 321-327.
[11]	Liao Z, Luo R, Li G, et al. Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo[J]. Theranostics, 2019, 9(14): 4084-4100.
[12]	Cheng X, Zhang G, Zhang L, et al. Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration[J]. J Cell Mol Med, 2018, 22(1): 261-276.
[13]	Lu K, Li H-y, Yang K, et al. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells[J]. Stem Cell Res Ther, 2017, 8(1): 108.
[14]	Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J]. Cytotherapy, 2006, 8(4): 315-317.
[15]	Phan J, Kumar P, Hao D, et al. Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy[J]. J Extracell Vesicles, 2018, 7(1): 1522236.
[16]	Keller S, Ridinger J, Rupp A-K, et al. Body fluid derived exosomes as a novel template for clinical diagnostics[J]. J Transl Med, 2011, 9: 86.
[17]	Lässer C, Eldh M, Lötvall J. Isolation and Characterization of RNA-Containing Exosomes[J]. J Vis Exp, 2012(59): e3037.
[18]	Lasser C, O′Neil SE, Ekerljung L, et al. RNA-containing exosomes in human nasal secretions[J]. Am J Rhinol Allergy, 2011, 25(2): 89-93.
[19]	Théry C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids[J]. Curr Protoc Cell Biol, 2006, Chapter 3: Unit 3.22.
[20]	Simons M, Raposo G. Exosomes-vesicular carriers for intercellular communication[J]. Curr Opin Cell Biol, 2009, 21(4): 575-581.
[21]	Mathivanan S, Fahner CJ, Reid GE, et al. ExoCarta 2012: database of exosomal proteins, RNA and lipids[J]. Nucleic Acids Res, 2012, 40(D1): D1241-D1244.
[22]	Basu J, Ludlow JW. Exosomes for repair, regeneration and rejuvenation[J]. Expert Opin Biol Ther, 2016, 16(4): 489-506.
[23]	Lai RC, Yeo RWY, Tan SS, et al. Mesenchymal Stem Cell Exosomes: The Future MSC-Based Therapy？[J]. Stem Cell Res Ther, 2013: 39-61.
[24]	Lai RC, Tan SS, Teh BJ, et al. Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome[J]. Int J Proteomics, 2012, 2012: 971907.
[25]	Lai RC, Yeo RW, Lim SK. Mesenchymal stem cell exosomes[J]. Semin Cell Dev Biol, 2015, 40: 82-88.
[26]	Wang K, Chen TT, Ying XZ, et al. Ligustilide alleviated IL-1 beta induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo[J]. Int Immunopharmacol, 2019, 69: 398-407.
[27]	Hingert D, Ekstrom K, Aldridge J, et al. Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures[J]. Stem Cell Res Ther, 2020, 11(1): 323.
[28]	龚东亮，付文芹. 间充质干细胞外泌体上调Mir-21调控HO-1机制促进椎间盘退变的修复[J]. 解剖学研究， 2020, 42(2): 140-145.
[29]	Qi L, Wang R, Shi Q, et al. Umbilical cord mesenchymal stem cell conditioned medium restored the expression of collagen II and aggrecan in nucleus pulposus mesenchymal stem cells exposed to high glucose[J]. J Bone Miner Metab, 2019, 37(3): 455-466.
[30]	蒋长青，蓝蔚仁，李海音，等. 大鼠骨髓间充质干细胞来源外泌体对退变髓核细胞的影响[J]. 中国脊柱脊髓杂志， 2019, 29(2): 147-155.
[31]	Zhu G, Yang X, Peng C, et al. Exosomal miR-532-5p from bone marrow mesenchymal stem cells reduce intervertebral disc degeneration by targeting RASSF5[J]. Exp Cell Res, 2020, 393(2): 112109.
[32]	Zhu L, Shi Y, Liu L, et al. Mesenchymal stem cells-derived exosomes ameliorate nucleus pulposus cells apoptosis via delivering miR-142-3p: therapeutic potential for intervertebral disc degenerative diseases[J]. Cell Cycle, 2020, 19(14): 1727-1739.
[33]	Yuan Q, Wang X, Liu L, et al. Exosomes derived from human placental mesenchymal stromal cells carrying antagomiR-4450 alleviate intervertebral disc degeneration through upregulation of ZNF121[J]. Stem Cells Dev, 2020, 29(16): 1038-1058.
[34]	Li ZQ, Kong L, Liu C, et al. Human bone marrow mesenchymal stem cell-derived exosomes attenuate IL-1beta-induced annulus fibrosus cell damage[J]. Am J Med Sci, 2020, 360(6): 693-700.
[35]	Liu Y, Li Y, Nan LP, et al. Insights of stem cell-based endogenous repair of intervertebral disc degeneration[J]. World J Stem Cells, 2020, 12(4): 266-276.
[36]	Xia C, Zeng Z, Fang B, et al. Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects[J]. Free Radic Biol Med, 2019, 143: 1-15.
[37]	Zhang J, Zhang J, Zhang Y, et al. Mesenchymal stem cells-derived exosomes ameliorate intervertebral disc degeneration through inhibiting pyroptosis[J]. J Cell Mol Med, 2020, 24(20): 11742-11754.

MSC-Exos的作用	机制
ECM的合成与降解	抑制降解ECM的MMP-1/3合成及直接促进ECM合成
髓核细胞凋亡	miRNA-21参与PTEN-PI3K/Akt通路
	miR-532-5p与RASSF-5靶基因结合
	miR-142-3p与MLK3结合，抑制MAPK信号通路
	miR-4450与靶基因ZNF121结合
	降低内质网应激的关键分子CHOP水平
纤维环细胞凋亡	抑制PI3K/AKT/mTOR信号通路介导的细胞自噬
软骨终板细胞凋亡	miRNA-31-5p与靶基因ATF6结合，降低内质网应激水平
炎症反应	miRNA-410与NLRP3的mRNA特异性结合，抑制炎性小体NLRP3生成
	抑制PGE-2、IL-6及COX-2等炎性因子活化
	抑制PI3K/AKT/mTOR信号通路介导的细胞自噬

MSC-Exos的作用	机制
ECM的合成与降解	抑制降解ECM的MMP-1/3合成及直接促进ECM合成
髓核细胞凋亡	miRNA-21参与PTEN-PI3K/Akt通路
	miR-532-5p与RASSF-5靶基因结合
	miR-142-3p与MLK3结合，抑制MAPK信号通路
	miR-4450与靶基因ZNF121结合
	降低内质网应激的关键分子CHOP水平
纤维环细胞凋亡	抑制PI3K/AKT/mTOR信号通路介导的细胞自噬
软骨终板细胞凋亡	miRNA-31-5p与靶基因ATF6结合，降低内质网应激水平
炎症反应	miRNA-410与NLRP3的mRNA特异性结合，抑制炎性小体NLRP3生成
	抑制PGE-2、IL-6及COX-2等炎性因子活化
	抑制PI3K/AKT/mTOR信号通路介导的细胞自噬

Please choose a citation manager

Content to export