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Review Article

New Hope for Intervertebral Disc Degeneration: Bone Marrow Mesenchymal Stem Cells and Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Transplantation

Author(s): Xiao-bo Zhang*, Xiang-yi Chen, Jin Qi, Hai-yu Zhou, Xiao-bing Zhao, Yi-cun Hu, Rui-hao Zhang, De-chen Yu, Xi-dan Gao, Ke-ping Wang and Lin Ma

Volume 22, Issue 4, 2022

Published on: 11 October, 2021

Page: [291 - 302] Pages: 12

DOI: 10.2174/1566523221666211012092855

Price: $65

Abstract

Bone Marrow Mesenchymal Stem Cells (BMSCs), multidirectional cells with self-renewal capacity, can differentiate into many cell types and play essential roles in tissue healing and regenerative medicine. Cell experiments and in vivo research in animal models have shown that BMSCs can repair degenerative discs by promoting cell proliferation and expressing Extracellular Matrix (ECM) components, such as type II collagen and protein-polysaccharides. Delaying or reversing the Intervertebral Disc Degeneration (IDD) process at an etiological level may be an effective strategy. However, despite increasingly in-depth research, some deficiencies in cell transplantation timing and strategy remain, preventing the clinical application of cell transplantation. Exosomes exhibit the characteristics of the mother cells from which they are secreted and can inhibit Nucleus Pulposus Cell (NPC) apoptosis and delay IDD through intercellular communication. Furthermore, the use of exosomes effectively avoids problems associated with cell transplantation, such as immune rejection. This manuscript introduces almost all of the BMSCs and exosomes derived from BMSCs (BMSCs-Exos) described in the IDD literature. Many challenges regarding the use of cell transplantation and therapeutic exosome intervention for IDD remain to be overcome.

Keywords: Bone marrow mesenchymal stem cells (BMSCs), exosome, intervertebral disc degeneration (IDD), transplantation, therapy, low back pain (LBP).

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[1]
Zhao L, Manchikanti L, Kaye AD, Abd-Elsayed A. Treatment of discogenic low back pain: Current treatment strategies and future options-a literature review. Curr Pain Headache Rep 2019; 23(11): 86.
[http://dx.doi.org/10.1007/s11916-019-0821-x] [PMID: 31707499]
[2]
Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat Rev Rheumatol 2014; 10(1): 44-56.
[http://dx.doi.org/10.1038/nrrheum.2013.160] [PMID: 24166242]
[3]
Cazzanelli P, Wuertz-Kozak K. MicroRNAs in intervertebral disc degeneration, apoptosis, inflammation, and mechanobiology. Int J Mol Sci 2020; 21(10): E3601.
[http://dx.doi.org/10.3390/ijms21103601] [PMID: 32443722]
[4]
Dowdell J, Erwin M, Choma T, Vaccaro A, Iatridis J, Cho SK. Intervertebral disk degeneration and repair. Neurosurgery 2017; 80(3S): S46-54.
[http://dx.doi.org/10.1093/neuros/nyw078] [PMID: 28350945]
[5]
Baliga S, Treon K, Craig NJ. Low back pain: current surgical approaches. Asian Spine J 2015; 9(4): 645-57.
[http://dx.doi.org/10.4184/asj.2015.9.4.645] [PMID: 26240729]
[6]
Vlaeyen JWS, Maher CG, Wiech K, et al. Low back pain. Nat Rev Dis Primers 2018; 4(1): 52.
[http://dx.doi.org/10.1038/s41572-018-0052-1] [PMID: 30546064]
[7]
Shim EK, Lee JS, Kim DE, et al. Autogenous mesenchymal stem cells from the vertebral body enhance intervertebral disc regeneration via paracrine interaction: An in vitro pilot study. Cell Transplant 2016; 25(10): 1819-32.
[http://dx.doi.org/10.3727/096368916X691420] [PMID: 27075568]
[8]
Han C, Jiang C, Yu C, Shen H. Differentiation of transforming growth factor β1-induced mesenchymal stem cells into nucleus pulposus-like cells under simulated microgravity conditions. Cell Mol Biol 2015; 61(2): 50-5.
[PMID: 26025402]
[9]
Feng G, Zhao X, Liu H, et al. Transplantation of mesenchymal stem cells and nucleus pulposus cells in a degenerative disc model in rabbits: A comparison of 2 cell types as potential candidates for disc regeneration. J Neurosurg Spine 2011; 14(3): 322-9.
[http://dx.doi.org/10.3171/2010.11.SPINE10285] [PMID: 21250814]
[10]
Clemente JM, Clemente JV. Clinico-biomechanical issues and dynamic stabilization when considering stem cell treatment for degenerative disc disease. Transplantation 2013; 95(2): e1.
[http://dx.doi.org/10.1097/TP.0b013e3182772337] [PMID: 23325008]
[11]
Wang Z, Perez-Terzic CM, Smith J, et al. Efficacy of intervertebral disc regeneration with stem cells - A systematic review and meta-analysis of animal controlled trials. Gene 2015; 564(1): 1-8.
[http://dx.doi.org/10.1016/j.gene.2015.03.022] [PMID: 25796605]
[12]
Liu C, Tsai AL, Li PC, Huang CW, Wu CC. Endothelial differentiation of bone marrow mesenchyme stem cells applicable to hypoxia and increased migration through Akt and NFκB signals. Stem Cell Res Ther 2017; 8(1): 29.
[http://dx.doi.org/10.1186/s13287-017-0470-0] [PMID: 28173835]
[13]
Teixeira GQ, Pereira CL, Ferreira JR, et al. Immunomodulation of human mesenchymal stem/stromal cells in intervertebral disc degeneration: Insights from a proinflammatory/degenerative ex vivo model. Spine 2018; 43(12): E673-82.
[http://dx.doi.org/10.1097/BRS.0000000000002494] [PMID: 29189572]
[14]
Wangler S, Peroglio M, Menzel U, et al. Mesenchymal stem cell homing into intervertebral discs enhances the Tie2-positive progenitor cell population, prevents cell death, and induces a proliferative response. Spine 2019; 44(23): 1613-22.
[http://dx.doi.org/10.1097/BRS.0000000000003150] [PMID: 31730570]
[15]
Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal stem cell migration and tissue repair. Cells 2019; 8(8): 784.
[http://dx.doi.org/10.3390/cells8080784] [PMID: 31357692]
[16]
Ying J, Han Z, Zeng Y, et al. Evaluation of intervertebral disc regeneration with injection of mesenchymal stem cells encapsulated in PEGDA-microcryogel delivery system using quantitative T2 mapping: A study in canines. Am J Transl Res 2019; 11(4): 2028-41.
[PMID: 31105815]
[17]
Zhou Y, Hu X, Zheng X, et al. Differentiation potential of mesenchymal stem cells derived from adipose tissue vs bone marrow toward annulus fibrosus cells in vitro. Curr Stem Cell Res Ther 2017; 12(5): 432-9.
[http://dx.doi.org/10.2174/1574888X12666170214093955] [PMID: 28201959]
[18]
Yim RL, Lee JT, Bow CH, et al. A systematic review of the safety and efficacy of mesenchymal stem cells for disc degeneration: insights and future directions for regenerative therapeutics. Stem Cells Dev 2014; 23(21): 2553-67.
[http://dx.doi.org/10.1089/scd.2014.0203] [PMID: 25050446]
[19]
Sakai D, Mochida J, Yamamoto Y, et al. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: A potential therapeutic model for disc degeneration. Biomaterials 2003; 24(20): 3531-41.
[http://dx.doi.org/10.1016/S0142-9612(03)00222-9] [PMID: 12809782]
[20]
Risbud MV, Albert TJ, Guttapalli A, et al. Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy. Spine 2004; 29(23): 2627-32.
[http://dx.doi.org/10.1097/01.brs.0000146462.92171.7f] [PMID: 15564911]
[21]
Li X, Wu A, Han C, et al. Bone marrow-derived mesenchymal stem cells in three-dimensional co-culture attenuate degeneration of nucleus pulposus cells. Aging (Albany NY) 2019; 11(20): 9167-87.
[http://dx.doi.org/10.18632/aging.102390] [PMID: 31666429]
[22]
Yang H, Tian W, Wang S, et al. TSG-6 secreted by bone marrow mesenchymal stem cells attenuates intervertebral disc degeneration by inhibiting the TLR2/NF-κB signaling pathway. Lab Invest 2018; 98(6): 755-72.
[http://dx.doi.org/10.1038/s41374-018-0036-5] [PMID: 29483622]
[23]
Shi P, Chee A, Liu W, Chou PH, Zhu J, An HS. Therapeutic effects of cell therapy with neonatal human dermal fibroblasts and rabbit dermal fibroblasts on disc degeneration and inflammation. Spine J 2019; 19(1): 171-81.
[http://dx.doi.org/10.1016/j.spinee.2018.08.005] [PMID: 30142460]
[24]
Chiang ER, Ma HL, Wang JP, et al. Use of allogeneic hypoxic mesenchymal stem cells for treating disc degeneration in rabbits. J Orthopaed Res 2019; 37(6): 1440-50.
[http://dx.doi.org/10.1002/jor.24342]
[25]
Yi Z, Guanjun T, Lin C, Zifeng P. Effects of transplantation of hTIMP-1-expressing bone marrow mesenchymal stem cells on the extracellular matrix of degenerative intervertebral discs in an in vivo rabbit model. Spine 2014; 39(11): E669-75.
[http://dx.doi.org/10.1097/BRS.0000000000000316] [PMID: 24718065]
[26]
Mac Sweeney R, McAuley DF. Mesenchymal stem cell therapy in acute lung injury: Is it time for a clinical trial? Thorax 2012; 67(6): 475-6.
[http://dx.doi.org/10.1136/thoraxjnl-2011-201309] [PMID: 22504891]
[27]
Kebriaei P, Isola L, Bahceci E, et al. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant 2009; 15(7): 804-11.
[http://dx.doi.org/10.1016/j.bbmt.2008.03.012] [PMID: 19539211]
[28]
Jang MJ, Kim HS, Lee HG, et al. Placenta-derived mesenchymal stem cells have an immunomodulatory effect that can control acute graft-versus-host disease in mice. Acta Haematol 2013; 129(4): 197-206.
[http://dx.doi.org/10.1159/000345267] [PMID: 23257958]
[29]
Chhabra P, Brayman KL. Stem cell therapy to cure type 1 diabetes: from hype to hope. Stem Cells Transl Med 2013; 2(5): 328-36.
[http://dx.doi.org/10.5966/sctm.2012-0116] [PMID: 23572052]
[30]
Fisher SA, Doree C, Mathur A, Taggart DP, Martin-Rendon E. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst Rev 2016; 12(12): CD007888.
[http://dx.doi.org/10.1002/14651858.CD007888.pub3] [PMID: 28012165]
[31]
Mochida J, Sakai D, Nakamura Y, Watanabe T, Yamamoto Y, Kato S. Intervertebral disc repair with activated nucleus pulposus cell transplantation: A three-year, prospective clinical study of its safety. Eur Cell Mater 2015; 29: 202-12.
[http://dx.doi.org/10.22203/eCM.v029a15] [PMID: 25794529]
[32]
Henriksson HB, Papadimitriou N, Hingert D, Baranto A, Lindahl A, Brisby H. The traceability of mesenchymal stromal cells after injection into degenerated discs in patients with low back pain. Stem Cells Dev 2019; 28(17): 1203-11.
[http://dx.doi.org/10.1089/scd.2019.0074] [PMID: 31237488]
[33]
Migliorini F, Rath B, Tingart M, Baroncini A, Quack V, Eschweiler J. Autogenic mesenchymal stem cells for intervertebral disc regeneration. Int Orthop 2019; 43(4): 1027-36.
[http://dx.doi.org/10.1007/s00264-018-4218-y] [PMID: 30415465]
[34]
Meisel HJ, Agarwal N, Hsieh PC, et al. Cell therapy for treatment of intervertebral disc degeneration: A systematic review. Global Spine J 2019; 9(1)(Suppl.): 39S-52S.
[http://dx.doi.org/10.1177/2192568219829024] [PMID: 31157145]
[35]
Nakashima S, Matsuyama Y, Takahashi K, et al. Regeneration of intervertebral disc by the intradiscal application of cross-linked hyaluronate hydrogel and cross-linked chondroitin sulfate hydrogel in a rabbit model of intervertebral disc injury. Biomed Mater Eng 2009; 19(6): 421-9.
[http://dx.doi.org/10.3233/BME-2009-0608] [PMID: 20231795]
[36]
Wang F, Nan LP, Zhou SF, et al. Injectable hydrogel combined with nucleus pulposus-derived mesenchymal stem cells for the treatment of degenerative intervertebral disc in rats. Stem Cells Int 2019; 2019: 8496025.
[http://dx.doi.org/10.1155/2019/8496025] [PMID: 31737077]
[37]
Vickers L, Thorpe AA, Snuggs J, Sammon C, Le Maitre CL. Mesenchymal stem cell therapies for intervertebral disc degeneration: Consideration of the degenerate niche. JOR Spine 2019; 2(2): e1055.
[http://dx.doi.org/10.1002/jsp2.1055] [PMID: 31463465]
[38]
Varma DM, DiNicolas MS, Nicoll SB. Injectable, redox-polymerized carboxymethylcellulose hydrogels promote nucleus pulposus-like extracellular matrix elaboration by human MSCs in a cell density-dependent manner. Stem Cells Int 2018; 33(4): 576-89.
[http://dx.doi.org/10.1177/0885328218805216] [PMID: 30326804]
[39]
Zhang Zq, Wang Cs, Yang P, Wang Kz. Mesenchymal stem cells induced by microencapsulated chondrocytes on repairing of intervertebral disc degeneration. Orthop Surg 2018; 10: 328-36.
[40]
Naqvi SM, Gansau J, Gibbons D, Buckley CT. In vitro co-culture and ex vivo organ culture assessment of primed and cryopreserved stromal cell microcapsules for intervertebral disc regeneration. Eur Cell Mater 2019; 37: 134-52.
[41]
Zhang H, Yu S, Zhao X, Mao Z, Gao C. Stromal cell-derived factor-1α-encapsulated albumin/heparin nanoparticles for induced stem cell migration and intervertebral disc regeneration in vivo. Acta Biomater 2018; 72: 217-27.
[http://dx.doi.org/10.1016/j.actbio.2018.03.032] [PMID: 29597025]
[42]
Yan HS, Hang C, Chen SW, Wang KK, Bo P. Salvianolic acid B combined with mesenchymal stem cells contributes to nucleus pulposus regeneration. Connect Tissue Res 2020; 61(5): 435-44.
[http://dx.doi.org/10.1080/03008207.2019.1611794] [PMID: 31023105]
[43]
Liu Y, Li JM, Hu YG. Transplantation of gene-modified nucleus pulposus cells reverses rabbit intervertebral disc degeneration. Chin Med J (Engl) 2011; 124(16): 2431-7.
[PMID: 21933582]
[44]
Wang HC, Jin CH, Kong J, et al. The research of transgenic human nucleus pulposus cell transplantation in the treatment of lumbar disc degeneration. Kaohsiung J Med Sci 2019; 35(8): 486-92.
[http://dx.doi.org/10.1002/kjm2.12084] [PMID: 31091017]
[45]
Song X, Peng S. [Transplantation of transforming growth factor beta3 gene-modified nucleus pulposus cells for intervertebral disc degeneration in rabbits]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2012; 26(7): 790-5.
[PMID: 22905612]
[46]
Fang Z, Yang Q, Luo W, et al. Differentiation of GFP-Bcl-2-engineered mesenchymal stem cells towards a nucleus pulposus-like phenotype under hypoxia in vitro. Biochem Biophys Res Commun 2013; 432(3): 444-50.
[http://dx.doi.org/10.1016/j.bbrc.2013.01.127] [PMID: 23416353]
[47]
Zhao Y, Jia Z, Huang S, et al. Age-related changes in nucleus pulposus mesenchymal stem cells: An in vitro study in rats. Stem Cells Int 2017; 2017: 6761572.
[http://dx.doi.org/10.1155/2017/6761572] [PMID: 28396688]
[48]
Jia Z, Yang P, Wu Y, et al. Comparison of biological characteristics of nucleus pulposus mesenchymal stem cells derived from non-degenerative and degenerative human nucleus pulposus. Exp Ther Med 2017; 13(6): 3574-80.
[http://dx.doi.org/10.3892/etm.2017.4398] [PMID: 28588682]
[49]
Sakai D, Andersson GB. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions. Nat Rev Rheumatol 2015; 11(4): 243-56.
[http://dx.doi.org/10.1038/nrrheum.2015.13] [PMID: 25708497]
[50]
Feng C, Liu H, Yang Y, Huang B, Zhou Y. Growth and differentiation factor-5 contributes to the structural and functional maintenance of the intervertebral disc. Cell Physiol Biochem 2015; 35(1): 1-16.
[http://dx.doi.org/10.1159/000369670] [PMID: 25547527]
[51]
Hodgkinson T, Shen B, Diwan A, Hoyland JA, Richardson SM. Therapeutic potential of growth differentiation factors in the treatment of degenerative disc diseases. JOR Spine 2019; 2(1): e1045.
[http://dx.doi.org/10.1002/jsp2.1045] [PMID: 31463459]
[52]
Hodgkinson T, Stening JZ, White LJ, Shakesheff KM, Hoyland JA, Richardson SM. Microparticles for controlled growth differentiation factor 6 delivery to direct adipose stem cell-based nucleus pulposus regeneration. J Tissue Eng Regen Med 2019; 13(8): 1406-17.
[http://dx.doi.org/10.1002/term.2882] [PMID: 31066515]
[53]
Naqvi SM, Buckley CT. Differential response of encapsulated nucleus pulposus and bone marrow stem cells in isolation and coculture in alginate and chitosan hydrogels. Tissue Eng Part A 2015; 21(1-2): 288-99.
[http://dx.doi.org/10.1089/ten.tea.2013.0719] [PMID: 25060596]
[54]
Tsujimoto T, Sudo H, Todoh M, et al. An acellular bioresorbable ultra-purified alginate gel promotes intervertebral disc repair: A preclinical proof-of-concept study. EBioMedicine 2018; 37: 521-34.
[http://dx.doi.org/10.1016/j.ebiom.2018.10.055] [PMID: 30389504]
[55]
Sakai D. Future perspectives of cell-based therapy for intervertebral disc disease. Eur Spine Soc 2008; 17: 452-8.
[http://dx.doi.org/10.1007/s00586-008-0743-5]
[56]
Perez-Cruet M, Beeravolu N, McKee C, et al. Potential of human nucleus pulposus-like cells derived from umbilical cord to treat degenerative disc disease. Neurosurgery 2019; 84(1): 272-83.
[http://dx.doi.org/10.1093/neuros/nyy012] [PMID: 29490072]
[57]
Wang W, Wang Y, Deng G, et al. Transplantation of hypoxic-preconditioned bone mesenchymal stem cells retards intervertebral disc degeneration via enhancing implanted cell survival and migration in rats. Stem Cells Int 2018; 2018: 7564159.
[http://dx.doi.org/10.1155/2018/7564159] [PMID: 29535780]
[58]
Maidhof R, Rafiuddin A, Chowdhury F, Jacobsen T, Chahine NO. Timing of mesenchymal stem cell delivery impacts the fate and therapeutic potential in intervertebral disc repair. J Orthop Res 2017; 35(1): 32-40.
[http://dx.doi.org/10.1002/jor.23350] [PMID: 27334230]
[59]
Liu Y, Li Y, Huang ZN, et al. The effect of intervertebral disc degenerative change on biological characteristics of nucleus pulposus mesenchymal stem cell: an in vitro study in rats. Connect Tissue Res 2019; 60(4): 376-88.
[http://dx.doi.org/10.1080/03008207.2019.1570168] [PMID: 31119993]
[60]
Colombier P, Clouet J, Hamel O, Lescaudron L, Guicheux J. The lumbar intervertebral disc: from embryonic development to degeneration. Joint Bone Spine 2014; 81(2): 125-9.
[http://dx.doi.org/10.1016/j.jbspin.2013.07.012] [PMID: 23932724]
[61]
Liu J, Tao H, Wang H, et al. Biological behavior of human nucleus pulposus mesenchymal stem cells in response to changes in the acidic environment during intervertebral disc degeneration. Stem Cells Dev 2017; 26(12): 901-11.
[http://dx.doi.org/10.1089/scd.2016.0314] [PMID: 28298159]
[62]
Liang H, Chen S, Huang D, Deng X, Ma K, Shao Z. Effect of compression loading on human nucleus pulposus-derived mesenchymal stem cells. Stem Cells Int 2018; 2018: 1481243.
[http://dx.doi.org/10.1155/2018/1481243] [PMID: 30402107]
[63]
Vaudreuil N, Henrikson K, Pohl P, et al. Photopolymerizable biogel scaffold seeded with mesenchymal stem cells: safety and efficacy evaluation of novel treatment for intervertebral disc degeneration. Nat Rev Rheumatol 2019; 37(6): 1451-9.
[http://dx.doi.org/10.1002/jor.24208] [PMID: 30561043]
[64]
Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 2009; 9(8): 581-93.
[http://dx.doi.org/10.1038/nri2567] [PMID: 19498381]
[65]
Zhao T, Sun F, Liu J, et al. Emerging role of mesenchymal stem cell-derived exosomes in regenerative medicine. Curr Stem Cell Res Ther 2019; 14(6): 482-94.
[http://dx.doi.org/10.2174/1574888X14666190228103230] [PMID: 30819086]
[66]
Pegtel DM, Gould SJ. Exosomes. Annu Rev Biochem 2019; 88: 487-514.
[http://dx.doi.org/10.1146/annurev-biochem-013118-111902] [PMID: 31220978]
[67]
Abels ER, Breakefield XO. Introduction to extracellular vesicles: Biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol 2016; 36(3): 301-12.
[http://dx.doi.org/10.1007/s10571-016-0366-z] [PMID: 27053351]
[68]
Liu W, Li L, Rong Y, et al. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater 2020; 103: 196-212.
[http://dx.doi.org/10.1016/j.actbio.2019.12.020] [PMID: 31857259]
[69]
Dorronsoro A, Robbins PD. Regenerating the injured kidney with human umbilical cord mesenchymal stem cell-derived exosomes. Stem Cell Res Ther 2013; 4(2): 39.
[http://dx.doi.org/10.1186/scrt187] [PMID: 23680102]
[70]
Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 2019; 9: 19.
[http://dx.doi.org/10.1186/s13578-019-0282-2] [PMID: 30815248]
[71]
Lu K, Li HY, 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. Stem Cell Res Ther 2017; 8(1): 108.
[http://dx.doi.org/10.1186/s13287-017-0563-9] [PMID: 28486958]
[72]
Jafari D, Malih S, Eslami SS, et al. The relationship between molecular content of mesenchymal stem cells derived exosomes and their potentials: Opening the way for exosomes based therapeutics. Biochimie 2019; 165: 76-89.
[http://dx.doi.org/10.1016/j.biochi.2019.07.009] [PMID: 31302163]
[73]
Nagai M, Sho M, Akahori T, Nakagawa K, Nakamura K. Application of liquid biopsy for surgical management of pancreatic cancer. Ann Gastroenterol Surg 2020; 4(3): 216-23.
[http://dx.doi.org/10.1002/ags3.12317] [PMID: 32490335]
[74]
Lässer C, Alikhani VS, Ekström K, et al. Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages. J Transl Med 2011; 9: 9.
[http://dx.doi.org/10.1186/1479-5876-9-9] [PMID: 21235781]
[75]
Lässer C. Identification and analysis of circulating exosomal microRNA in human body fluids. Methods Mol Biol 2013; 1024: 109-28.
[http://dx.doi.org/10.1007/978-1-62703-453-1_9] [PMID: 23719946]
[76]
Zhang S, Hou Y, Yang J, et al. Application of mesenchymal stem cell exosomes and their drug-loading systems in acute liver failure. J Cell Mol Med 2020; 24(13): 7082-93.
[http://dx.doi.org/10.1111/jcmm.15290] [PMID: 32492261]
[77]
Zhang K, Shao CX, Zhu JD, et al. Exosomes function as nanoparticles to transfer miR-199a-3p to reverse chemoresistance to cisplatin in hepatocellular carcinoma. Biosci Rep 2020; 40(7): BSR20194026.
[http://dx.doi.org/10.1042/BSR20194026] [PMID: 32463473]
[78]
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9(6): 654-9.
[http://dx.doi.org/10.1038/ncb1596] [PMID: 17486113]
[79]
Jerez S, Araya H, Thaler R, et al. Proteomic analysis of exosomes and exosome-free conditioned media from human osteosarcoma cell lines reveals secretion of proteins related to tumor progression. J Cell Biochem 2017; 118(2): 351-60.
[http://dx.doi.org/10.1002/jcb.25642] [PMID: 27356893]
[80]
Xu JF, Wang YP, Zhang SJ, et al. Exosomes containing differential expression of microRNA and mRNA in osteosarcoma that can predict response to chemotherapy. Oncotarget 2017; 8(44): 75968-78.
[http://dx.doi.org/10.18632/oncotarget.18373] [PMID: 29100284]
[81]
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. Stem Cell Res Ther 2017; 8(1): 189.
[http://dx.doi.org/10.1186/s13287-017-0632-0] [PMID: 28807034]
[82]
Cai H, Yang X, Gao Y, et al. Exosomal microRNA-9-3p secreted from BMSCs downregulates ESM1 to suppress the development of bladder cancer. Mol Ther Nucleic Acids 2019; 18: 787-800.
[http://dx.doi.org/10.1016/j.omtn.2019.09.023] [PMID: 31734559]
[83]
Biswas S, Mandal G, Roy Chowdhury S, et al. Exosomes produced by mesenchymal stem cells drive differentiation of myeloid cells into immunosuppressive M2-polarized macrophages in breast cancer. J Immunol 2019; 203(12): 3447-60.
[http://dx.doi.org/10.4049/jimmunol.1900692] [PMID: 31704881]
[84]
Bai Y, Han YD, Yan XL, et al. Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury. Biochem Biophys Res Commun 2018; 500(2): 310-7.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.065] [PMID: 29654765]
[85]
Harrell CR, Simovic Markovic B, Fellabaum C, et al. Therapeutic potential of mesenchymal stem cell-derived exosomes in the treatment of eye diseases. Adv Exp Med Biol 2018; 1089: 47-57.
[http://dx.doi.org/10.1007/5584_2018_219] [PMID: 29774506]
[86]
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 Cell Mol Med 2018; 22(1): 261-76.
[http://dx.doi.org/10.1111/jcmm.13316] [PMID: 28805297]
[87]
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. Theranostics 2019; 9(14): 4084-100.
[http://dx.doi.org/10.7150/thno.33638] [PMID: 31281533]
[88]
Song Y, Wang Y, Zhang Y, et al. Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells. J Cell Mol Med 2017; 21(7): 1373-87.
[http://dx.doi.org/10.1111/jcmm.13067] [PMID: 28224704]
[89]
Zhang J, Zhang J, Zhang Y, et al. Mesenchymal stem cells-derived exosomes ameliorate intervertebral disc degeneration through inhibiting pyroptosis. J Cell Mol Med 2020; 24(20): 11742-54.
[http://dx.doi.org/10.1111/jcmm.15784] [PMID: 32860495]
[90]
Xia C, Zeng Z, Fang B, et al. Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects. Free Radic Biol Med 2019; 143: 1-15.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.07.026] [PMID: 31351174]
[91]
Zhu G, Yang X, Peng C, Yu L, Hao Y. Exosomal miR-532-5p from bone marrow mesenchymal stem cells reduce intervertebral disc degeneration by targeting RASSF5. Exp Cell Res 2020; 393(2): 112109.
[http://dx.doi.org/10.1016/j.yexcr.2020.112109] [PMID: 32464126]
[92]
Zhu L, Shi Y, Liu L, Wang H, Shen P, Yang H. Mesenchymal stem cells-derived exosomes ameliorate nucleus pulposus cells apoptosis via delivering miR-142-3p: therapeutic potential for intervertebral disc degenerative diseases. Cell Cycle 2020; 19(14): 1727-39.
[http://dx.doi.org/10.1080/15384101.2020.1769301] [PMID: 32635856]
[93]
Li ZQ, Kong L, Liu C, Xu HG. Human bone marrow mesenchymal stem cell-derived exosomes attenuate IL-1β-induced annulus fibrosus cell damage. Am J Med Sci 2020; 360(6): 693-700.
[http://dx.doi.org/10.1016/j.amjms.2020.07.025] [PMID: 32771218]
[94]
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. Mol Ther Nucleic Acids 2020; 22: 601-14.
[http://dx.doi.org/10.1016/j.omtn.2020.09.026] [PMID: 33230460]
[95]
Hingert D, Ekström K, Aldridge J, Crescitelli R, Brisby H. Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures. Stem Cell Res Ther 2020; 11(1): 323.
[http://dx.doi.org/10.1186/s13287-020-01832-2] [PMID: 32727623]
[96]
Lan WR, Pan S, Li HY, et al. Inhibition of the notch1 pathway promotes the effects of nucleus pulposus cell-derived exosomes on the differentiation of mesenchymal stem cells into nucleus pulposus-like cells in rats. Stem Cells Int 2019; 2019: 8404168.
[http://dx.doi.org/10.1155/2019/8404168] [PMID: 31249601]
[97]
Chen S, Luo M, Kou H, Shang G, Ji Y, Liu H. A review of gene therapy delivery systems for intervertebral disc degeneration. Curr Pharm Biotechnol 2020; 21(3): 194-205.
[http://dx.doi.org/10.2174/1389201020666191024171618] [PMID: 31749423]
[98]
Yamashita T, Takahashi Y, Nishikawa M, Takakura Y. Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. Eur J Pharm Biopharm 2016; 98: 1-8.
[http://dx.doi.org/10.1016/j.ejpb.2015.10.017] [PMID: 26545617]
[99]
Tang YT, Huang YY, Zheng L, et al. Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum. Int J Mol Med 2017; 40(3): 834-44.
[http://dx.doi.org/10.3892/ijmm.2017.3080] [PMID: 28737826]
[100]
Lőrincz ÁM, Timár CI, Marosvári KA, et al. Effect of storage on physical and functional properties of extracellular vesicles derived from neutrophilic granulocytes. J Extracell Vesicles 2014; 3: 25465.
[http://dx.doi.org/10.3402/jev.v3.25465] [PMID: 25536933]
[101]
Qin B, Zhang Q, Hu XM, et al. How does temperature play a role in the storage of extracellular vesicles? J Cell Physiol 2020; 235(11): 7663-80.
[http://dx.doi.org/10.1002/jcp.29700] [PMID: 32324279]
[102]
Maroto R, Zhao Y, Jamaluddin M, et al. Effects of storage temperature on airway exosome integrity for diagnostic and functional analyses. J Extracell Vesicles 2017; 6(1): 1359478.
[http://dx.doi.org/10.1080/20013078.2017.1359478] [PMID: 28819550]
[103]
Akers JC, Ramakrishnan V, Yang I, et al. Optimizing preservation of extracellular vesicular miRNAs derived from clinical cerebrospinal fluid. Cancer Biomark 2016; 17(2): 125-32.
[http://dx.doi.org/10.3233/CBM-160609] [PMID: 27062568]
[104]
Jin Y, Chen K, Wang Z, et al. DNA in serum extracellular vesicles is stable under different storage conditions. BMC Cancer 2016; 16(1): 753.
[http://dx.doi.org/10.1186/s12885-016-2783-2] [PMID: 27662833]
[105]
Hu ZL, Li HY, Chang X, et al. Exosomes derived from stem cells as an emerging therapeutic strategy for intervertebral disc degeneration. World J Stem Cells 2020; 12(8): 803-13.
[http://dx.doi.org/10.4252/wjsc.v12.i8.803] [PMID: 32952860]
[106]
Yamashita T, Takahashi Y, Takakura Y. Possibility of exosome-based therapeutics and challenges in production of exosomes eligible for therapeutic application. Biol Pharm Bull 2018; 41(6): 835-42.
[http://dx.doi.org/10.1248/bpb.b18-00133] [PMID: 29863072]

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