Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

General Review Article

A New Paradigm in Spinal Cord Injury Therapy: from Cell-free Treatment to Engineering Modifications

Author(s): Bo Qin, Xi-min Hu, Yan-xia Huang, Rong-hua Yang* and Kun Xiong*

Volume 23, Issue 5, 2024

Published on: 22 May, 2023

Page: [656 - 673] Pages: 18

DOI: 10.2174/1871527322666230418090857

Price: $65

Abstract

Spinal cord injury (SCI) is an intractable and poorly prognostic neurological disease, and current treatments are still unable to cure it completely and avoid sequelae. Extracellular vesicles (EVs), as important carriers of intercellular communication and pharmacological effects, are considered to be the most promising candidates for SCI therapy because of their low toxicity and immunogenicity, their ability to encapsulate endogenous bioactive molecules (e.g., proteins, lipids, and nucleic acids), and their ability to cross the blood-brain/cerebrospinal barriers. However, poor targeting, low retention rate, and limited therapeutic efficacy of natural EVs have bottlenecked EVs-based SCI therapy. A new paradigm for SCI treatment will be provided by engineering modified EVs. Furthermore, our limited understanding of the role of EVs in SCI pathology hinders the rational design of novel EVbased therapeutic approaches. In this study, we review the pathophysiology after SCI, especially the multicellular EVs-mediated crosstalk; briefly describe the shift from cellular to cell-free therapies for SCI treatment; discuss and analyze the issues related to the route and dose of EVs administration; summarize and present the common strategies for EVs drug loading in the treatment of SCI and point out the shortcomings of these drug loading methods; finally, we analyze and highlight the feasibility and advantages of bio-scaffold-encapsulated EVs for SCI treatment, providing scalable insights into cell-free therapy for SCI.

Keywords: Extracellular vesicles, engineering, spinal cord injury, drug loading, biomaterials, sustained delivery.

« Previous
Graphical Abstract
[1]
Aziz I, Che Ramli MD, Mohd Zain NS, Sanusi J. Behavioral and histopathological study of changes in spinal cord injured rats supplemented with Spirulina platensis. Evid Based Complement Alternat Med 2014; 2014: 1-8.
[http://dx.doi.org/10.1155/2014/871657] [PMID: 25152764]
[2]
Sykova E, Cizkova D, Kubinova S. Mesenchymal stem cells in treatment of spinal cord injury and amyotrophic lateral sclerosis. Front Cell Dev Biol 2021; 9: 695900.
[http://dx.doi.org/10.3389/fcell.2021.695900] [PMID: 34295897]
[3]
Bhat IA, T B S , Somal A, et al. An allogenic therapeutic strategy for canine spinal cord injury using mesenchymal stem cells. J Cell Physiol 2019; 234(3): 2705-18.
[http://dx.doi.org/10.1002/jcp.27086] [PMID: 30132873]
[4]
Vismara I, Papa S, Rossi F, Forloni G, Veglianese P. Current options for cell therapy in spinal cord injury. Trends Mol Med 2017; 23(9): 831-49.
[http://dx.doi.org/10.1016/j.molmed.2017.07.005] [PMID: 28811172]
[5]
Streijger F, So K, Manouchehri N, et al. A direct comparison between norepinephrine and phenylephrine for augmenting spinal cord perfusion in a porcine model of spinal cord injury. J Neurotrauma 2018; 35(12): 1345-57.
[http://dx.doi.org/10.1089/neu.2017.5285] [PMID: 29338544]
[6]
Hawryluk G, Whetstone W, Saigal R, et al. Mean arterial blood pressure correlates with neurological recovery after human spinal cord injury: Analysis of high frequency physiologic data. J Neurotrauma 2015; 32(24): 1958-67.
[http://dx.doi.org/10.1089/neu.2014.3778] [PMID: 25669633]
[7]
Wutte C, Klein B, Becker J, et al. Earlier decompression (< 8 hours) results in better neurological and functional outcome after traumatic thoracolumbar spinal cord injury. J Neurotrauma 2019; 36(12): 2020-7.
[http://dx.doi.org/10.1089/neu.2018.6146] [PMID: 30489193]
[8]
Fehlings MG, Vaccaro A, Wilson JR, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: Results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS One 2012; 7(2): e32037.
[http://dx.doi.org/10.1371/journal.pone.0032037] [PMID: 22384132]
[9]
Yang M, Yin X, Liu S, et al. Letter: Ultra-early (<12 Hours) surgery correlates with higher rate of american spinal injury association impairment scale conversion after cervical spinal cord injury. Neurosurgery 2019; 85(2): E399-400.
[http://dx.doi.org/10.1093/neuros/nyz154] [PMID: 31173146]
[10]
Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990; 322(20): 1405-11.
[http://dx.doi.org/10.1056/NEJM199005173222001] [PMID: 2278545]
[11]
Bracken MB, Shepard MJ, Hellenbrand KG, et al. Methylprednisolone and neurological function 1 year after spinal cord injury. J Neurosurg 1985; 63(5): 704-13.
[http://dx.doi.org/10.3171/jns.1985.63.5.0704] [PMID: 3903070]
[12]
Jones CF, Newell RS, Lee JHT, Cripton PA, Kwon BK. The pressure distribution of cerebrospinal fluid responds to residual compression and decompression in an animal model of acute spinal cord injury. Spine 2012; 37(23): E1422-31.
[http://dx.doi.org/10.1097/BRS.0b013e31826ba7cd] [PMID: 22869059]
[13]
Squair JW, Bélanger LM, Tsang A, et al. Spinal cord perfusion pressure predicts neurologic recovery in acute spinal cord injury. Neurology 2017; 89(16): 1660-7.
[http://dx.doi.org/10.1212/WNL.0000000000004519] [PMID: 28916535]
[14]
O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol 2020; 21(10): 585-606.
[http://dx.doi.org/10.1038/s41580-020-0251-y] [PMID: 32457507]
[15]
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 Extracell Vesicles 2018; 7(1): 1535750.
[http://dx.doi.org/10.1080/20013078.2018.1535750] [PMID: 30637094]
[16]
Kumar A, Kumar S. Inhibition of extracellular vesicle pathway using neutral sphingomyelinase inhibitors as a neuroprotective treatment for brain injury. Neural Regen Res 2021; 16(12): 2349-52.
[http://dx.doi.org/10.4103/1673-5374.313014] [PMID: 33907005]
[17]
Couch Y, Buzàs EI, Di Vizio D, et al. A brief history of nearly Everything – The rise and rise of extracellular vesicles. J Extracell Vesicles 2021; 10(14): e12144.
[http://dx.doi.org/10.1002/jev2.12144] [PMID: 34919343]
[18]
Hu Y, Sun Y, Wan C, et al. Microparticles: biogenesis, characteristics and intervention therapy for cancers in preclinical and clinical research. J Nanobiotechnology 2022; 20(1): 189.
[http://dx.doi.org/10.1186/s12951-022-01358-0] [PMID: 35418077]
[19]
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018; 19(4): 213-28.
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[20]
Rufino-Ramos D, Albuquerque PR, Carmona V, Perfeito R, Nobre RJ, Pereira de Almeida L. Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases. J Control Release 2017; 262: 247-58.
[http://dx.doi.org/10.1016/j.jconrel.2017.07.001] [PMID: 28687495]
[21]
Snow DM, Beller JA. Proteoglycans: Road signs for neurite outgrowth. Neural Regen Res 2014; 9(4): 343-55.
[http://dx.doi.org/10.4103/1673-5374.128235] [PMID: 25206822]
[22]
Li M, Shibata A, Li C, et al. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. J Neurosci Res 1996; 46(4): 404-14.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19961115)46:4<404:AID-JNR2>3.0.CO;2-K] [PMID: 8950700]
[23]
Domeniconi M, Cao Z, Spencer T, et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 2002; 35(2): 283-90.
[http://dx.doi.org/10.1016/S0896-6273(02)00770-5] [PMID: 12160746]
[24]
Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001; 409(6818): 341-6.
[http://dx.doi.org/10.1038/35053072] [PMID: 11201742]
[25]
Morales II II, Toscano-Tejeida D, Ibarra A. Non pharmacological strategies to promote spinal cord regeneration: A view on some individual or combined approaches. Curr Pharm Des 2016; 22(6): 720-7.
[http://dx.doi.org/10.2174/1381612822666151204001103] [PMID: 26635267]
[26]
Kumar H, Ropper AE, Lee SH, Han I. Propitious therapeutic modulators to prevent blood-spinal cord barrier disruption in spinal cord injury. Mol Neurobiol 2017; 54(5): 3578-90.
[http://dx.doi.org/10.1007/s12035-016-9910-6] [PMID: 27194298]
[27]
Oudega M. Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair. Cell Tissue Res 2012; 349(1): 269-88.
[http://dx.doi.org/10.1007/s00441-012-1440-6] [PMID: 22592628]
[28]
Ulndreaj A, Chio JCT, Ahuja CS, Fehlings MG. Modulating the immune response in spinal cord injury. Expert Rev Neurother 2016; 16(10): 1127-9.
[http://dx.doi.org/10.1080/14737175.2016.1207532] [PMID: 27352883]
[29]
Nakamura M, Houghtling RA, MacArthur L, Bayer BM, Bregman BS. Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord. Exp Neurol 2003; 184(1): 313-25.
[http://dx.doi.org/10.1016/S0014-4886(03)00361-3] [PMID: 14637102]
[30]
Kwon BK, Streijger F, Fallah N, et al. Cerebrospinal fluid biomarkers to stratify injury severity and predict outcome in human traumatic spinal cord injury. J Neurotrauma 2017; 34(3): 567-80.
[http://dx.doi.org/10.1089/neu.2016.4435] [PMID: 27349274]
[31]
Biglari B, Swing T, Child C, et al. A pilot study on temporal changes in IL-1β and TNF-α serum levels after spinal cord injury: The serum level of TNF-α in acute SCI patients as a possible marker for neurological remission. Spinal Cord 2015; 53(7): 510-4.
[http://dx.doi.org/10.1038/sc.2015.28] [PMID: 25753492]
[32]
Leal-Filho M. Spinal cord injury: From inflammation to glial scar. Surg Neurol Int 2011; 2(1): 112.
[http://dx.doi.org/10.4103/2152-7806.83732] [PMID: 21886885]
[33]
Liddelow SA, Barres BA. Reactive astrocytes: Production, function, and therapeutic potential. Immunity 2017; 46(6): 957-67.
[http://dx.doi.org/10.1016/j.immuni.2017.06.006] [PMID: 28636962]
[34]
Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: Time for reassessment. F1000Prime Rep 2014; 6: 13.
[http://dx.doi.org/10.12703/P6-13] [PMID: 24669294]
[35]
Anderson MA, Burda JE, Ren Y, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature 2016; 532(7598): 195-200.
[http://dx.doi.org/10.1038/nature17623] [PMID: 27027288]
[36]
Jia Y-J, Zhou Y, Wen L-L, et al. Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis. Neural Regen Res 2022; 17(1): 194-202.
[http://dx.doi.org/10.4103/1673-5374.314323] [PMID: 34100456]
[37]
Xu BP, Yao M, Wang XT, et al. Mechanism of macrophage polarization on spinal cord injury. Zhongguo Gu Shang 2018; 31(1): 88-92.
[PMID: 29533045]
[38]
Venkatesh K, Ghosh SK, Mullick M, Manivasagam G, Sen D. Spinal cord injury: Pathophysiology, treatment strategies, associated challenges, and future implications. Cell Tissue Res 2019; 377(2): 125-51.
[http://dx.doi.org/10.1007/s00441-019-03039-1] [PMID: 31065801]
[39]
Siebert JR, Osterhout DJ. The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes. J Neurochem 2011; 119(1): 176-88.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07370.x] [PMID: 21848846]
[40]
Yang T, Dai Y, Chen G, Cui S. Dissecting the dual role of the glial scar and scar-forming astrocytes in spinal cord injury. Front Cell Neurosci 2020; 14: 78.
[http://dx.doi.org/10.3389/fncel.2020.00078] [PMID: 32317938]
[41]
Gaudet AD, Fonken LK. Glial cells shape pathology and repair after spinal cord injury. Neurotherapeutics 2018; 15(3): 554-77.
[http://dx.doi.org/10.1007/s13311-018-0630-7] [PMID: 29728852]
[42]
Gensel JC, Nakamura S, Guan Z, van Rooijen N, Ankeny DP, Popovich PG. Macrophages promote axon regeneration with concurrent neurotoxicity. J Neurosci 2009; 29(12): 3956-68.
[http://dx.doi.org/10.1523/JNEUROSCI.3992-08.2009] [PMID: 19321792]
[43]
Ahuja CS, Nori S, Tetreault L, et al. Traumatic spinal cord injury—repair and regeneration. Neurosurgery 2017; 80(3S): S9-S22.
[http://dx.doi.org/10.1093/neuros/nyw080] [PMID: 28350947]
[44]
Liao HY, Wang ZQ, Ran R, Zhou KS, Ma CW, Zhang HH. Biological functions and therapeutic potential of autophagy in spinal cord injury. Front Cell Dev Biol 2021; 9: 761273.
[http://dx.doi.org/10.3389/fcell.2021.761273] [PMID: 34988074]
[45]
Guo T, Deng Y, Dong L, Ren L, He H. Autophagy elicits neuroprotection at the subacute phase of transient cerebral ischaemia but has few effects on neurological outcomes after permanent ischaemic stroke in rats. Curr Med Sci 2021; 41(4): 803-14.
[http://dx.doi.org/10.1007/s11596-021-2400-8] [PMID: 34403106]
[46]
Juryńczyk M, Jacob A, Fujihara K, Palace J. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: Practical considerations. Pract Neurol 2019; 19(3): 187-95.
[http://dx.doi.org/10.1136/practneurol-2017-001787] [PMID: 30530724]
[47]
Reindl M, Waters P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol 2019; 15(2): 89-102.
[http://dx.doi.org/10.1038/s41582-018-0112-x] [PMID: 30559466]
[48]
Tai W, Wu W, Wang LL, et al. In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury. Cell Stem Cell 2021; 28(5): 923-937.e4.
[http://dx.doi.org/10.1016/j.stem.2021.02.009] [PMID: 33675690]
[49]
Liu P, Zhang Z, Wang Q, Guo R, Mei W. Lithium chloride facilitates autophagy following spinal cord injury via ERK-dependent pathway. Neurotox Res 2017; 32(4): 535-43.
[http://dx.doi.org/10.1007/s12640-017-9758-1] [PMID: 28593525]
[50]
Dutta D, Khan N, Wu J, Jay SM. Extracellular vesicles as an emerging frontier in spinal cord injury pathobiology and therapy. Trends Neurosci 2021; 44(6): 492-506.
[http://dx.doi.org/10.1016/j.tins.2021.01.003] [PMID: 33581883]
[51]
Kumar A, Stoica BA, Loane DJ, et al. Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury. J Neuroinflammation 2017; 14(1): 47.
[http://dx.doi.org/10.1186/s12974-017-0819-4] [PMID: 28292310]
[52]
Prada I, Gabrielli M, Turola E, et al. Glia-to-neuron transfer of miRNAs via extracellular vesicles: A new mechanism underlying inflammation-induced synaptic alterations. Acta Neuropathol 2018; 135(4): 529-50.
[http://dx.doi.org/10.1007/s00401-017-1803-x] [PMID: 29302779]
[53]
You Y, Borgmann K, Edara VV, Stacy S, Ghorpade A, Ikezu T. Activated human astrocyte‐derived extracellular vesicles modulate neuronal uptake, differentiation and firing. J Extracell Vesicles 2020; 9(1): 1706801.
[http://dx.doi.org/10.1080/20013078.2019.1706801] [PMID: 32002171]
[54]
Datta Chaudhuri A, Dasgheyb RM, DeVine LR, Bi H, Cole RN, Haughey NJ. Stimulus‐dependent modifications in astrocyte‐derived extracellular vesicle cargo regulate neuronal excitability. Glia 2020; 68(1): 128-44.
[http://dx.doi.org/10.1002/glia.23708] [PMID: 31469478]
[55]
Chaudhuri AD, Dastgheyb RM, Yoo SW, et al. TNFα and IL-1β modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons. Cell Death Dis 2018; 9(3): 363.
[http://dx.doi.org/10.1038/s41419-018-0369-4] [PMID: 29507357]
[56]
Sekine Y, Lindborg JA, Strittmatter SM. A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration. J Biol Chem 2020; 295(8): 2175-83.
[http://dx.doi.org/10.1074/jbc.RA119.009896] [PMID: 31748413]
[57]
Goncalves MB, Malmqvist T, Clarke E, et al. Neuronal RARβ signaling modulates PTEN activity directly in neurons and via exosome transfer in astrocytes to prevent glial scar formation and induce spinal cord regeneration. j neurosci 2015; 35(47): 15731-45.
[http://dx.doi.org/10.1523/JNEUROSCI.1339-15.2015] [PMID: 26609164]
[58]
Kastner A, Matarazzo V. Neuroprotective and neurorestorative processes after spinal cord injury: The case of the bulbospinal respiratory neurons. Neural Plast 2016; 2016: 1-15.
[http://dx.doi.org/10.1155/2016/7692602] [PMID: 27563469]
[59]
Guo S, Redenski I, Levenberg S. Spinal cord repair: From cells and tissue engineering to extracellular vesicles. Cells 2021; 10(8): 1872.
[http://dx.doi.org/10.3390/cells10081872] [PMID: 34440641]
[60]
Lu P, Dulin JN. Bridging the injured spinal cord with neural stem cells. Neural Regen Res 2014; 9(3): 229-31.
[http://dx.doi.org/10.4103/1673-5374.128212] [PMID: 25206804]
[61]
Rosenzweig ES, Brock JH, Lu P, et al. Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat Med 2018; 24(4): 484-90.
[http://dx.doi.org/10.1038/nm.4502] [PMID: 29480894]
[62]
Cofano F, Boido M, Monticelli M, et al. Mesenchymal stem cells for spinal cord injury: Current options, limitations, and future of cell therapy. Int J Mol Sci 2019; 20(11): 2698.
[http://dx.doi.org/10.3390/ijms20112698] [PMID: 31159345]
[63]
Ullah M, Liu DD, Thakor AS. Mesenchymal stromal cell homing: Mechanisms and strategies for improvement. iScience 2019; 15: 421-38.
[http://dx.doi.org/10.1016/j.isci.2019.05.004] [PMID: 31121468]
[64]
Qiao L, Hu S, Huang K, et al. Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs. Theranostics 2020; 10(8): 3474-87.
[http://dx.doi.org/10.7150/thno.39434] [PMID: 32206102]
[65]
Ferreira JR, Teixeira GQ, Santos SG, Barbosa MA, Almeida-Porada G, Gonçalves RM. Mesenchymal stromal cell secretome: Influencing therapeutic potential by cellular pre-conditioning. Front Immunol 2018; 9: 2837.
[http://dx.doi.org/10.3389/fimmu.2018.02837] [PMID: 30564236]
[66]
Witwer KW, Van Balkom BWM, Bruno S, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles 2019; 8(1): 1609206.
[http://dx.doi.org/10.1080/20013078.2019.1609206] [PMID: 31069028]
[67]
Liu W, Ma Z, Li J, Kang X. Mesenchymal stem cell-derived exosomes: Therapeutic opportunities and challenges for spinal cord injury. Stem Cell Res Ther 2021; 12(1): 102.
[http://dx.doi.org/10.1186/s13287-021-02153-8] [PMID: 33536064]
[68]
Pan D, Liu W, Zhu S, et al. Potential of different cells-derived exosomal microRNA cargos for treating spinal cord injury. J Orthop Translat 2021; 31: 33-40.
[http://dx.doi.org/10.1016/j.jot.2021.09.008] [PMID: 34760623]
[69]
Liau LL, Looi QH, Chia WC, Subramaniam T, Ng MH, Law JX. Treatment of spinal cord injury with mesenchymal stem cells. Cell Biosci 2020; 10(1): 112.
[http://dx.doi.org/10.1186/s13578-020-00475-3] [PMID: 32983406]
[70]
Cheng L, Sharples RA, Scicluna BJ, Hill AF. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles 2014; 3(1): 23743.
[http://dx.doi.org/10.3402/jev.v3.23743] [PMID: 24683445]
[71]
Koga Y, Yasunaga M, Moriya Y, et al. Exosome can prevent RNase from degrading microRNA in feces. J Gastrointest Oncol 2011; 2(4): 215-22.
[PMID: 22811855]
[72]
Furlan JC, Sakakibara BM, Miller WC, Krassioukov AV. Global incidence and prevalence of traumatic spinal cord injury. Can J Neurol Sci 2013; 40(4): 456-64.
[http://dx.doi.org/10.1017/S0317167100014530] [PMID: 23786727]
[73]
Felekkis K, Touvana E, Stefanou Ch, Deltas C. microRNAs: A newly described class of encoded molecules that play a role in health and disease. Hippokratia 2010; 14(4): 236-40.
[PMID: 21311629]
[74]
Davis AE. Mechanisms of traumatic brain injury: Biomechanical, structural and cellular considerations. Crit Care Nurs Q 2000; 23(3): 1-13.
[http://dx.doi.org/10.1097/00002727-200011000-00002] [PMID: 11852934]
[75]
Lee Y. EL Andaloussi S, Wood MJA. Exosomes and microvesicles: Extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet 2012; 21(R1): R125-34.
[http://dx.doi.org/10.1093/hmg/dds317] [PMID: 22872698]
[76]
Yelamanchili SV, Chaudhuri AD, Chen L-N, Xiong H, Fox HS. MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease. Cell Death Dis 2010; 1(9): e77.
[http://dx.doi.org/10.1038/cddis.2010.56] [PMID: 21170291]
[77]
Jiang D, Gong F, Ge X, et al. Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes. J Nanobiotechnology 2020; 18(1): 105.
[http://dx.doi.org/10.1186/s12951-020-00665-8] [PMID: 32711535]
[78]
Li C, Qin T, Liu Y, et al. Microglia-derived exosomal microRNA-151-3p enhances functional healing after spinal cord injury by attenuating neuronal apoptosis via regulating the p53/p21/CDK1 signaling pathway. Front Cell Dev Biol 2022; 9: 783017.
[http://dx.doi.org/10.3389/fcell.2021.783017] [PMID: 35127706]
[79]
Lange S. Peptidylarginine deiminases and extracellular vesicles: Prospective drug targets and biomarkers in central nervous system diseases and repair. Neural Regen Res 2021; 16(5): 934-8.
[http://dx.doi.org/10.4103/1673-5374.297058] [PMID: 33229732]
[80]
Gupta D, Zickler AM, El Andaloussi S. Dosing extracellular vesicles. Adv Drug Deliv Rev 2021; 178: 113961.
[http://dx.doi.org/10.1016/j.addr.2021.113961] [PMID: 34481030]
[81]
Rong Y, Liu W, Wang J, et al. Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy. Cell Death Dis 2019; 10(5): 340.
[http://dx.doi.org/10.1038/s41419-019-1571-8] [PMID: 31000697]
[82]
Zhong D, Cao Y, Li CJ, et al. Neural stem cell-derived exosomes facilitate spinal cord functional recovery after injury by promoting angiogenesis. Exp Biol Med (Maywood) 2020; 245(1): 54-65.
[http://dx.doi.org/10.1177/1535370219895491] [PMID: 31903774]
[83]
Mohammed I, Ijaz S, Mokhtari T, et al. Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation. Metab Brain Dis 2020; 35(5): 809-18.
[http://dx.doi.org/10.1007/s11011-020-00563-w] [PMID: 32185593]
[84]
Ma K, Xu H, Zhang J, et al. Insulin-like growth factor-1 enhances neuroprotective effects of neural stem cell exosomes after spinal cord injury via an miR-219a-2-3p/YY1 mechanism. Aging 2019; 11(24): 12278-94.
[http://dx.doi.org/10.18632/aging.102568] [PMID: 31848325]
[85]
Romanelli P, Bieler L, Scharler C, et al. Extracellular vesicles can deliver anti-inflammatory and anti-scarring activities of mesenchymal stromal cells after spinal cord injury. Front Neurol 2019; 10: 1225.
[http://dx.doi.org/10.3389/fneur.2019.01225] [PMID: 31849808]
[86]
Yuan X, Wu Q, Wang P, et al. Exosomes derived from pericytes improve microcirculation and protect blood–spinal cord barrier after spinal cord injury in mice. Front Neurosci 2019; 13: 319.
[http://dx.doi.org/10.3389/fnins.2019.00319] [PMID: 31040762]
[87]
Fröhlich D, Kuo WP, Frühbeis C, et al. Multifaceted effects of oligodendroglial exosomes on neurons: Impact on neuronal firing rate, signal transduction and gene regulation. Philos Trans R Soc Lond B Biol Sci 2014; 369(1652): 20130510.
[http://dx.doi.org/10.1098/rstb.2013.0510] [PMID: 25135971]
[88]
Ge X, Guo M, Hu T, et al. Increased microglial exosomal miR-124-3p alleviates neurodegeneration and improves cognitive outcome after rmTBI. Mol Ther 2020; 28(2): 503-22.
[http://dx.doi.org/10.1016/j.ymthe.2019.11.017] [PMID: 31843449]
[89]
Ge X, Tang P, Rong Y, et al. Corrigendum to “Exosomal miR-155 from M1-polarized macrophages promotes EndoMT and impairs mitochondrial function via activating NF-kappaB signaling pathway in vascular endothelial cells after traumatic spinal cord injury”. Redox Biol 2021; 47: 102121.
[http://dx.doi.org/10.1016/j.redox.2021.102121] [PMID: 34475015]
[90]
Mu J, Li L, Wu J, et al. Hypoxia-stimulated mesenchymal stem cell-derived exosomes loaded by adhesive hydrogel for effective angiogenic treatment of spinal cord injury. Biomater Sci 2022; 10(7): 1803-11.
[http://dx.doi.org/10.1039/D1BM01722E] [PMID: 35234220]
[91]
Mu J, Wu J, Cao J, et al. Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes. Asian J Pharm Sci 2021; 16(6): 806-15.
[http://dx.doi.org/10.1016/j.ajps.2021.10.002] [PMID: 35027955]
[92]
Sheng X, Zhao J, Li M, et al. Bone marrow mesenchymal stem cell-derived exosomes accelerate functional recovery after spinal cord injury by promoting the phagocytosis of macrophages to clean myelin debris. Front Cell Dev Biol 2021; 9: 772205.
[http://dx.doi.org/10.3389/fcell.2021.772205] [PMID: 34820385]
[93]
Yong T, Wang D, Li X, et al. Extracellular vesicles for tumor targeting delivery based on five features principle. J Control Release 2020; 322: 555-65.
[http://dx.doi.org/10.1016/j.jconrel.2020.03.039] [PMID: 32246977]
[94]
Tominaga N, Kosaka N, Ono M, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier. Nat Commun 2015; 6(1): 6716.
[http://dx.doi.org/10.1038/ncomms7716] [PMID: 25828099]
[95]
Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 2016; 44(3): 450-62.
[http://dx.doi.org/10.1016/j.immuni.2016.02.015] [PMID: 26982353]
[96]
Betzer O, Perets N, Angel A, et al. In vivo neuroimaging of exosomes using gold nanoparticles. ACS Nano 2017; 11(11): 10883-93.
[http://dx.doi.org/10.1021/acsnano.7b04495] [PMID: 28960957]
[97]
Shahjin F, Chand S, Yelamanchili SV. Extracellular vesicles as drug delivery vehicles to the central nervous system. J Neuroimmune Pharmacol 2020; 15(3): 443-58.
[http://dx.doi.org/10.1007/s11481-019-09875-w] [PMID: 31485884]
[98]
Verweij FJ, Hyenne V, Van Niel G, Goetz JG. Extracellular vesicles: Catching the light in zebrafish. Trends Cell Biol 2019; 29(10): 770-6.
[http://dx.doi.org/10.1016/j.tcb.2019.07.007] [PMID: 31400828]
[99]
Morad G, Carman CV, Hagedorn EJ, et al. Tumor-derived extracellular vesicles breach the intact blood–brain barrier via transcytosis. ACS Nano 2019; 13(12): 13853-65.
[http://dx.doi.org/10.1021/acsnano.9b04397] [PMID: 31479239]
[100]
Xu M, Feng T, Liu B, et al. Engineered exosomes: Desirable target-tracking characteristics for cerebrovascular and neurodegenerative disease therapies. Theranostics 2021; 11(18): 8926-44.
[http://dx.doi.org/10.7150/thno.62330] [PMID: 34522219]
[101]
Xin H, Katakowski M, Wang F, et al. MicroRNA-17–92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke 2017; 48(3): 747-53.
[http://dx.doi.org/10.1161/STROKEAHA.116.015204] [PMID: 28232590]
[102]
Song Y, Li Z, He T, et al. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. Theranostics 2019; 9(10): 2910-23.
[http://dx.doi.org/10.7150/thno.30879] [PMID: 31244932]
[103]
Erdő F, Bors LA, Farkas D, Bajza Á, Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res Bull 2018; 143: 155-70.
[http://dx.doi.org/10.1016/j.brainresbull.2018.10.009] [PMID: 30449731]
[104]
Fu P, Zhang J, Li H, Mak M, Xu W, Tao Z. Extracellular vesicles as delivery systems at nano-/micro-scale. Adv Drug Deliv Rev 2021; 179: 113910.
[http://dx.doi.org/10.1016/j.addr.2021.113910] [PMID: 34358539]
[105]
Qiu X, Li Z, Han X, et al. Tumor-derived nanovesicles promote lung distribution of the therapeutic nanovector through repression of Kupffer cell-mediated phagocytosis. Theranostics 2019; 9(9): 2618-36.
[http://dx.doi.org/10.7150/thno.32363] [PMID: 31131057]
[106]
Lai CP, Mardini O, Ericsson M, et al. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 2014; 8(1): 483-94.
[http://dx.doi.org/10.1021/nn404945r] [PMID: 24383518]
[107]
Nishida-Aoki N, Tominaga N, Kosaka N, Ochiya T. Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake. J Extracell Vesicles 2020; 9(1): 1713527.
[http://dx.doi.org/10.1080/20013078.2020.1713527] [PMID: 32082512]
[108]
Gao B, Zhou S, Sun C, et al. Brain endothelial cell-derived exosomes induce neuroplasticity in rats with ischemia/reperfusion injury. ACS Chem Neurosci 2020; 11(15): 2201-13.
[http://dx.doi.org/10.1021/acschemneuro.0c00089] [PMID: 32574032]
[109]
Kim HJ, Seo SW, Chang JW, et al. Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: A phase 1 clinical trial. Alzheimers Dement 2015; 1(2): 95-102.
[http://dx.doi.org/10.1016/j.trci.2015.06.007] [PMID: 29854930]
[110]
Kou L, Yao Q, Sivaprakasam S, et al. Dual targeting of l -carnitine-conjugated nanoparticles to OCTN2 and ATB 0,+ to deliver chemotherapeutic agents for colon cancer therapy. Drug Deliv 2017; 24(1): 1338-49.
[http://dx.doi.org/10.1080/10717544.2017.1377316] [PMID: 28911246]
[111]
Kou L, Bhutia YD, Yao Q, He Z, Sun J, Ganapathy V. Transporter-guided delivery of nanoparticles to improve drug permeation across cellular barriers and drug exposure to selective cell types. Front Pharmacol 2018; 9: 27.
[http://dx.doi.org/10.3389/fphar.2018.00027] [PMID: 29434548]
[112]
Guo S, Perets N, Betzer O, et al. Intranasal delivery of mesenchymal stem cell derived exosomes loaded with phosphatase and tensin homolog siRNA repairs complete spinal cord injury. ACS Nano 2019; 13(9): 10015-28.
[http://dx.doi.org/10.1021/acsnano.9b01892] [PMID: 31454225]
[113]
Wu H, Hu K, Jiang X. From nose to brain: Understanding transport capacity and transport rate of drugs. Expert Opin Drug Deliv 2008; 5(10): 1159-68.
[http://dx.doi.org/10.1517/17425247.5.10.1159] [PMID: 18817519]
[114]
Nair A, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016; 7(2): 27-31.
[http://dx.doi.org/10.4103/0976-0105.177703] [PMID: 27057123]
[115]
Webber J, Clayton A. How pure are your vesicles? J Extracell Vesicles 2013; 2(1): 19861.
[http://dx.doi.org/10.3402/jev.v2i0.19861] [PMID: 24009896]
[116]
Rajan TS, Giacoppo S, Diomede F, et al. The secretome of periodontal ligament stem cells from MS patients protects against EAE. Sci Rep 2016; 6(1): 38743.
[http://dx.doi.org/10.1038/srep38743] [PMID: 27924938]
[117]
Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 2011; 19(10): 1769-79.
[http://dx.doi.org/10.1038/mt.2011.164] [PMID: 21915101]
[118]
Riazifar M, Mohammadi MR, Pone EJ, et al. Stem cell-derived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano 2019; 13(6): 6670-88.
[http://dx.doi.org/10.1021/acsnano.9b01004] [PMID: 31117376]
[119]
Casella G, Rasouli J, Boehm A, et al. Oligodendrocyte-derived extracellular vesicles as antigen-specific therapy for autoimmune neuroinflammation in mice. Sci Transl Med 2020; 12(568): eaba0599.
[http://dx.doi.org/10.1126/scitranslmed.aba0599] [PMID: 33148622]
[120]
Williams JL, Gatson NN, Smith KM, Almad A, McTigue DM, Whitacre CC. Serum exosomes in pregnancy-associated immune modulation and neuroprotection during CNS autoimmunity. Clin Immunol 2013; 149(2): 236-43.
[http://dx.doi.org/10.1016/j.clim.2013.04.005] [PMID: 23706172]
[121]
EL Andaloussi S, Mäger I, Breakefield XO, Wood MJA. Extracellular vesicles: Biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013; 12(5): 347-57.
[http://dx.doi.org/10.1038/nrd3978] [PMID: 23584393]
[122]
Gupta D, Liang X, Pavlova S, et al. Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging. J Extracell Vesicles 2020; 9(1): 1800222.
[http://dx.doi.org/10.1080/20013078.2020.1800222] [PMID: 32944187]
[123]
Varga Z, Gyurkó I, Pálóczi K, et al. Radiolabeling of extracellular vesicles with 99m Tc for quantitative in vivo imaging studies. Cancer Biother Radiopharm 2016; 31(5): 168-73.
[http://dx.doi.org/10.1089/cbr.2016.2009] [PMID: 27310303]
[124]
Wiklander OPB, Brennan MÁ, Lötvall J, Breakefield XO. EL Andaloussi S. Advances in therapeutic applications of extracellular vesicles. Sci Transl Med 2019; 11(492): eaav8521.
[http://dx.doi.org/10.1126/scitranslmed.aav8521] [PMID: 31092696]
[125]
Li D, Zhang P, Yao X, et al. Exosomes derived from miR-133b-modified mesenchymal stem cells promote recovery after spinal cord injury. Front Neurosci 2018; 12: 845.
[http://dx.doi.org/10.3389/fnins.2018.00845] [PMID: 30524227]
[126]
Feng J, Zhang Y, Zhu Z, Gu C, Waqas A, Chen L. Emerging exosomes and exosomal MiRNAs in spinal cord injury. Front Cell Dev Biol 2021; 9: 703989.
[http://dx.doi.org/10.3389/fcell.2021.703989] [PMID: 34307384]
[127]
Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol 2021; 16(7): 748-59.
[http://dx.doi.org/10.1038/s41565-021-00931-2] [PMID: 34211166]
[128]
Piffoux M, Silva AKA, Lugagne JB, Hersen P, Wilhelm C, Gazeau F. Extracellular vesicle production loaded with nanoparticles and drugs in a trade-off between loading, yield and purity: Towards a personalized drug delivery system. Adv Biosyst 2017; 1(5): 1700044.
[http://dx.doi.org/10.1002/adbi.201700044] [PMID: 32646153]
[129]
Schulz E, Goes A, Garcia R, et al. Biocompatible bacteria-derived vesicles show inherent antimicrobial activity. J Control Release 2018; 290: 46-55.
[http://dx.doi.org/10.1016/j.jconrel.2018.09.030] [PMID: 30292423]
[130]
de Jong OG, Kooijmans SAA, Murphy DE, et al. Drug delivery with extracellular vesicles: From imagination to innovation. Acc Chem Res 2019; 52(7): 1761-70.
[http://dx.doi.org/10.1021/acs.accounts.9b00109] [PMID: 31181910]
[131]
Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin 2017; 38(6): 754-63.
[http://dx.doi.org/10.1038/aps.2017.12] [PMID: 28392567]
[132]
Zhao L, Jiang X, Shi J, et al. Exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 protect spinal cords against transient ischemia. J Thorac Cardiovasc Surg 2019; 157(2): 508-17.
[http://dx.doi.org/10.1016/j.jtcvs.2018.07.095] [PMID: 30224076]
[133]
Li C, Li X, Zhao B, Wang C. Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord injury. Arch Physiol Biochem 2020; 126(4): 369-75.
[http://dx.doi.org/10.1080/13813455.2019.1691601] [PMID: 32141339]
[134]
Liu W, Rong Y, Wang J, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization. J Neuroinflammation 2020; 17(1): 47.
[http://dx.doi.org/10.1186/s12974-020-1726-7] [PMID: 32019561]
[135]
Colao IL, Corteling R, Bracewell D, Wall I. Manufacturing exosomes: A promising therapeutic platform. Trends Mol Med 2018; 24(3): 242-56.
[http://dx.doi.org/10.1016/j.molmed.2018.01.006] [PMID: 29449149]
[136]
Bartosh TJ, Ylöstalo JH, Mohammadipoor A, et al. Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci USA 2010; 107(31): 13724-9.
[http://dx.doi.org/10.1073/pnas.1008117107] [PMID: 20643923]
[137]
Cui X, Wang H, Guo H, et al. Transplantation of mesenchymal stem cells preconditioned with diazoxide, a mitochondrial ATP-sensitive potassium channel opener, promotes repair of myocardial infarction in rats. Tohoku J Exp Med 2010; 220(2): 139-47.
[http://dx.doi.org/10.1620/tjem.220.139] [PMID: 20139665]
[138]
Pessina A, Coccè V, Pascucci L, et al. Mesenchymal stromal cells primed with Paclitaxel attract and kill leukaemia cells, inhibit angiogenesis and improve survival of leukaemia-bearing mice. Br J Haematol 2013; 160(6): 766-78.
[http://dx.doi.org/10.1111/bjh.12196] [PMID: 23293837]
[139]
Wang Z, Zhang F, Wang L, Yao Y, Zhao Q, Gao X. Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt. Cell Biol Int 2009; 33(6): 665-74.
[http://dx.doi.org/10.1016/j.cellbi.2009.03.006] [PMID: 19376254]
[140]
Leroux L, Descamps B, Tojais NF, et al. Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway. Mol Ther 2010; 18(8): 1545-52.
[http://dx.doi.org/10.1038/mt.2010.108] [PMID: 20551912]
[141]
Wei L, Fraser JL, Lu ZY, Hu X, Yu SP. Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Neurobiol Dis 2012; 46(3): 635-45.
[http://dx.doi.org/10.1016/j.nbd.2012.03.002] [PMID: 22426403]
[142]
Heo SC, Jeon ES, Lee IH, Kim HS, Kim MB, Kim JH. Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms. J Invest Dermatol 2011; 131(7): 1559-67.
[http://dx.doi.org/10.1038/jid.2011.64] [PMID: 21451545]
[143]
Mendt M, Kamerkar S, Sugimoto H, et al. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 2018; 3(8): e99263.
[http://dx.doi.org/10.1172/jci.insight.99263] [PMID: 29669940]
[144]
Guitart K, Loers G, Buck F, Bork U, Schachner M, Kleene R. Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. Glia 2016; 64(6): 896-910.
[http://dx.doi.org/10.1002/glia.22963] [PMID: 26992135]
[145]
Xu L, Cao H, Xie Y, et al. Exosome-shuttled miR-92b-3p from ischemic preconditioned astrocytes protects neurons against oxygen and glucose deprivation. Brain Res 2019; 1717: 66-73.
[http://dx.doi.org/10.1016/j.brainres.2019.04.009] [PMID: 30986407]
[146]
Kim HY, Kumar H, Jo MJ, et al. Therapeutic efficacy-potentiated and diseased organ-targeting nanovesicles derived from mesenchymal stem cells for spinal cord injury treatment. Nano Lett 2018; 18: 4965-75.
[147]
Kooijmans SAA, Stremersch S, Braeckmans K, et al. Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J Control Release 2013; 172(1): 229-38.
[http://dx.doi.org/10.1016/j.jconrel.2013.08.014] [PMID: 23994516]
[148]
Lamichhane TN, Jeyaram A, Patel DB, et al. Oncogene knockdown via active loading of small RNAs into extracellular vesicles by sonication. Cell Mol Bioeng 2016; 9(3): 315-24.
[http://dx.doi.org/10.1007/s12195-016-0457-4] [PMID: 27800035]
[149]
Khayambashi P, Iyer J, Pillai S, Upadhyay A, Zhang Y, Tran S. Hydrogel encapsulation of mesenchymal stem cells and their derived exosomes for tissue engineering. Int J Mol Sci 2021; 22(2): 684.
[http://dx.doi.org/10.3390/ijms22020684] [PMID: 33445616]
[150]
Gutierrez-Aranda I, Ramos-Mejia V, Bueno C, et al. Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells 2010; 28(9): 1568-70.
[http://dx.doi.org/10.1002/stem.471] [PMID: 20641038]
[151]
Zhang Y, Wang D, Chen M, Yang B, Zhang F, Cao K. Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart. PLoS One 2011; 6(4): e19012.
[http://dx.doi.org/10.1371/journal.pone.0019012] [PMID: 21552563]
[152]
Riau AK, Ong HS, Yam GHF, Mehta JS. Sustained delivery system for stem cell-derived exosomes. Front Pharmacol 2019; 10: 1368.
[153]
Lin L, Du L. The role of secreted factors in stem cells-mediated immune regulation. Cell Immunol 2018; 326: 24-32.
[http://dx.doi.org/10.1016/j.cellimm.2017.07.010] [PMID: 28778535]
[154]
Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol 2013; 200(4): 373-83.
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
[155]
Schorey JS, Harding CV. Extracellular vesicles and infectious diseases: New complexity to an old story. J Clin Invest 2016; 126(4): 1181-9.
[http://dx.doi.org/10.1172/JCI81132] [PMID: 27035809]
[156]
Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014; 30(1): 255-89.
[http://dx.doi.org/10.1146/annurev-cellbio-101512-122326] [PMID: 25288114]
[157]
Smyth T, Kullberg M, Malik N, Smith-Jones P, Graner MW, Anchordoquy TJ. Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J Control Release 2015; 199: 145-55.
[http://dx.doi.org/10.1016/j.jconrel.2014.12.013] [PMID: 25523519]
[158]
Charoenviriyakul C, Takahashi Y, Morishita M, Matsumoto A, Nishikawa M, Takakura Y. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics. Eur J Pharm Sci 2017; 96: 316-22.
[http://dx.doi.org/10.1016/j.ejps.2016.10.009] [PMID: 27720897]
[159]
Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods 2015; 87: 3-10.
[http://dx.doi.org/10.1016/j.ymeth.2015.02.019] [PMID: 25766927]
[160]
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]
[161]
Willis GR, Kourembanas S, Mitsialis SA. Toward exosome-based therapeutics: Isolation, heterogeneity, and fit-for-purpose potency. Front Cardiovasc Med 2017; 4: 63.
[http://dx.doi.org/10.3389/fcvm.2017.00063] [PMID: 29062835]
[162]
Stephanopoulos N, Ortony JH, Stupp SI. Self-assembly for the synthesis of functional biomaterials. Acta Mater 2013; 61(3): 912-30.
[http://dx.doi.org/10.1016/j.actamat.2012.10.046] [PMID: 23457423]
[163]
Xiong Y, Chen L, Liu P, et al. All‐in‐One: Multifunctional hydrogel accelerates oxidative diabetic wound healing through timed‐release of exosome and fibroblast growth factor. Small 2022; 18(1): 2104229.
[http://dx.doi.org/10.1002/smll.202104229] [PMID: 34791802]
[164]
Wang M, Wang C, Chen M, et al. Efficient angiogenesis-based diabetic wound healing/skin reconstruction through bioactive antibacterial adhesive ultraviolet shielding nanodressing with exosome release. ACS Nano 2019; 13(9): 10279-93.
[http://dx.doi.org/10.1021/acsnano.9b03656] [PMID: 31483606]
[165]
Liu B, Lee BW, Nakanishi K, et al. Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells. Nat Biomed Eng 2018; 2(5): 293-303.
[http://dx.doi.org/10.1038/s41551-018-0229-7] [PMID: 30271672]
[166]
Yildirimer L, Zhang Q, Kuang S, et al. Engineering three-dimensional microenvironments towards in vitro disease models of the central nervous system. Biofabrication 2019; 11(3): 032003.
[http://dx.doi.org/10.1088/1758-5090/ab17aa] [PMID: 30965297]
[167]
Chen P, Zheng L, Wang Y, et al. Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration. Theranostics 2019; 9(9): 2439-59.
[http://dx.doi.org/10.7150/thno.31017] [PMID: 31131046]
[168]
Ding SQ, Chen J, Wang SN, et al. Identification of serum exosomal microRNAs in acute spinal cord injured rats. Exp Biol Med 2019; 244(14): 1149-61.
[http://dx.doi.org/10.1177/1535370219872759] [PMID: 31450959]
[169]
Ding SQ, Chen YQ, Chen J, et al. Serum exosomal microRNA transcriptome profiling in subacute spinal cord injured rats. Genomics 2020; 112(6): 5086-100.
[http://dx.doi.org/10.1016/j.ygeno.2019.09.021] [PMID: 32919018]
[170]
Khan NZ, Cao T, He J, et al. Spinal cord injury alters microRNA and CD81+ exosome levels in plasma extracellular nanoparticles with neuroinflammatory potential. Brain Behav Immun 2021; 92: 165-83.
[http://dx.doi.org/10.1016/j.bbi.2020.12.007] [PMID: 33307173]
[171]
Qin B, Hu X, Su Z, Zeng X, Ma H, Xiong K. Tissue-derived extracellular vesicles: Research progress from isolation to application. Pathol Res Pract 2021; 226: 153604.
[http://dx.doi.org/10.1016/j.prp.2021.153604] [PMID: 34500372]
[172]
Huang Y, Cheng L, Turchinovich A, et al. Influence of species and processing parameters on recovery and content of brain tissue‐derived extracellular vesicles. J Extracell Vesicles 2020; 9(1): 1785746.
[http://dx.doi.org/10.1080/20013078.2020.1785746] [PMID: 32944174]
[173]
Zhang Q, Wang J, Zhu L, et al. Ligustrazine attenuates hyperhomocysteinemia-induced alzheimer-like pathologies in rats. Curr Med Sci 2021; 41(3): 548-54.
[http://dx.doi.org/10.1007/s11596-021-2379-1] [PMID: 34169425]
[174]
Qin B, Zhang Q, Chen D, et al. Extracellular vesicles derived from mesenchymal stem cells: A platform that can be engineered. Histol Histopathol 2021; 36(6): 615-32.
[PMID: 33398872]
[175]
Qin B, Zhang Q, Hu X, 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]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy