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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Extracellular Vesicles as Therapeutics for Brain Injury and Disease

Author(s): Dinesh Upadhya* and Ashok K. Shetty

Volume 25, Issue 33, 2019

Page: [3500 - 3505] Pages: 6

DOI: 10.2174/1381612825666191014164950

Price: $65


Extracellular vesicles (EVs) are gaining tremendous importance in comprehending central nervous system (CNS) function and treating neurological disorders because of their role in intercellular communication and reparative processes, and suitability as drug delivery vehicles. Since EVs have lipid membranes, they cross the blood-brain barrier easily and communicate with target neurons and glia even deep inside the brain. EVs from various sources have been isolated, characterized, and tailored for promoting beneficial effects in conditions, such as brain injury and disease. Particularly, EVs isolated from mesenchymal stem cells and neural stem cells have shown promise for alleviating brain dysfunction after injury or disease. Such properties of stem cell-derived EVs have great importance for clinical applications, as EV therapy can avoid several concerns typically associated with cell therapy. This minireview confers the competence of EVs for improving brain function by modulating CNS injury and disease.

Keywords: Brain injury, extracellular vesicles, exosomes, mesenchymal stem cells, neural stem cells, neurodegenerative diseases.

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
[] [PMID: 30637094]
Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014; 30: 255-89.
[] [PMID: 25288114]
Xin H, Li Y, Liu Z, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 2013; 31(12): 2737-46.
[] [PMID: 23630198]
Doeppner TR, Herz J, Görgens A, et al. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Transl Med 2015; 4(10): 1131-43.
[] [PMID: 26339036]
Zhang Y, Chopp M, Meng Y, et al. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J Neurosurg 2015; 122(4): 856-67.
[] [PMID: 25594326]
Drommelschmidt K, Serdar M, Bendix I, et al. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Behav Immun 2017; 60: 220-32.
[] [PMID: 27847282]
Long Q, Upadhya D, Hattiangady B, et al. Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc Natl Acad Sci USA 2017; 114(17): E3536-45.
[] [PMID: 28396435]
Otero-Ortega L, Gómez de Frutos MC, Laso-García F, et al. Exosomes promote restoration after an experimental animal model of intracerebral hemorrhage. J Cereb Blood Flow Metab 2018; 38(5): 767-79.
[] [PMID: 28524762]
Xin H, Wang F, Li Y, et al. Secondary release of exosomes from astrocytes contributes to the increase in neural plasticity and improvement of functional recovery after stroke in rats treated with exosomes harvested from microRNA 133b-overexpressing multipotent mesenchymal stromal cells. Cell Transplant 2017; 26(2): 243-57.
[] [PMID: 27677799]
Osier N, Motamedi V, Edwards K, et al. Exosomes in acquired neurological disorders: new insights into pathophysiology and treatment. Mol Neurobiol 2018; 55(12): 9280-93.
[] [PMID: 29663285]
Webb RL, Kaiser EE, Jurgielewicz BJ, et al. Human neural stem cell extracellular vesicles improve recovery in a Porcine model of ischemic stroke. Stroke 2018; 49(5): 1248-56.
[] [PMID: 29650593]
de Rivero Vaccari JP, Brand F III, Adamczak S, et al. Exosome-mediated inflammasome signaling after central nervous system injury. J Neurochem 2016; 136(Suppl. 1): 39-48.
[] [PMID: 25628216]
Xiong Y, Mahmood A, Chopp M. Emerging potential of exosomes for treatment of traumatic brain injury. Neural Regen Res 2017; 12(1): 19-22.
[] [PMID: 28250732]
Yang Y, Ye Y, Su X, et al. MSCs-derived exosomes and neuroinflammation, neurogenesis and therapy of traumatic brain injury. Front Cell Neurosci 2017; 11: 55.
Chen J, Chopp M. Exosome therapy for stroke. Stroke 2018; 49(5): 1083-90.
[] [PMID: 29669873]
Zhang ZG, Buller B, Chopp M. Exosomes-beyond stem cells for restorative therapy in stroke and neurological injury. Nat Rev Neurol 2019; 15(4): 193-203.
[] [PMID: 30700824]
Chen KH, Chen CH, Wallace CG, et al. Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke. Oncotarget 2016; 7(46): 74537-56.
[] [PMID: 27793019]
Ophelders DR, Wolfs TG, Jellema RK, et al. Mesenchymal stromal cell-derived extracellular vesicles protect the fetal brain after hypoxia-ischemia. Stem Cells Transl Med 2016; 5(6): 754-63.
[] [PMID: 27160705]
Yu B, Zhang X, Li X. Exosomes derived from mesenchymal stem cells. Int J Mol Sci 2014; 15(3): 4142-57.
[] [PMID: 24608926]
Bang OY, Kim EH. Mesenchymal stem cell-derived extracellular vesicle therapy for stroke: challenges and progress. Front Neurol 2019; 10: 211.
[] [PMID: 30915025]
Nalamolu KR, Venkatesh I, Mohandass A, et al. Exosomes treatment mitigates ischemic brain damage but does not improve post-stroke neurological outcome. Cell Physiol Biochem 2019; 52(6): 1280-91.
[] [PMID: 31026391]
Ezquer F, Quintanilla ME, Morales P, et al. Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking. Addict Biol 2018; 24(5): 994-1007.
[] [PMID: 30239077]
Perets N, Hertz S, London M, Offen D. Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice. Mol Autism 2018; 9: 57.
[] [PMID: 30479733]
Narbute K, Piļipenko V, Pupure J, et al. Intranasal administration of extracellular vesicles derived from human teeth stem cells improves motor symptoms and normalizes tyrosine hydroxylase expression in the substantia nigra and striatum of the 6- hydroxydopamine-treated rats. Stem Cells Transl Med 2019; 8(5): 490-9.
[] [PMID: 30706999]
Blom IE, Goldschmeding R, Leask A. Gene regulation of connective tissue growth factor: new targets for antifibrotic therapy? Matrix Biol 2002; 21(6): 473-82.
[] [PMID: 12392758]
Leeuwis JW, Nguyen TQ, Theunissen MG, et al. Connective tissue growth factor is associated with a stable atherosclerotic plaque phenotype and is involved in plaque stabilization after stroke. Stroke 2010; 41(12): 2979-81.
[] [PMID: 20966418]
Xin H, Katakowski M, Wang F, et al. MicroRNA cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke 2017; 48(3): 747-53.
[] [PMID: 28232590]
Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab 2013; 33(11): 1711-5.
[] [PMID: 23963371]
Venkat P, Chen J, Chopp M. Exosome-mediated amplification of endogenous brain repair mechanisms and brain and systemic organ interaction in modulating neurological outcome after stroke. J Cereb Blood Flow Metab 2018; 38(12): 2165-78.
[] [PMID: 29888985]
Otero-Ortega L, Laso-García F, Gómez-de Frutos MD, et al. White matter repair after extracellular vesicles administration in an experimental animal model of subcortical stroke. Sci Rep 2017; 7: 44433.
[] [PMID: 28300134]
Webb RL, Kaiser EE, Scoville SL, et al. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model. Transl Stroke Res 2018; 9(5): 530-9.
[] [PMID: 29285679]
Nalamolu KR, Venkatesh I, Mohandass A, et al. Exosomes secreted by the cocultures of normal and oxygen-glucose-deprived stem cells improve post-stroke outcome. Neuromolecular Med 2019.
[] [PMID: 31077035]
Han Y, Seyfried D, Meng Y, et al. Multipotent mesenchymal stromal cell-derived exosomes improve functional recovery after experimental intracerebral hemorrhage in the rat. J Neurosurg 2018; 1-11.
[] [PMID: 30028267]
McCrory P, Meeuwisse WH, Aubry M, et al. Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport held in Zurich, November 2012. Br J Sports Med 2013; 47(5): 250-8.
[] [PMID: 23479479]
Blennow K, Brody DL, Kochanek PM, et al. Traumatic brain injuries. Nat Rev Dis Primers 2016; 2: 16084.
[] [PMID: 27853132]
Zhang Y, Chopp M, Zhang ZG, et al. Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury. Neurochem Int 2017; 111: 69-81.
[] [PMID: 27539657]
Kim DK, Nishida H, An SY, Shetty AK, Bartosh TJ, Prockop DJ. Chromatographically isolated CD63+CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. Proc Natl Acad Sci USA 2016; 113(1): 170-5.
[] [PMID: 26699510]
Leutgeb S, Leutgeb JK. Pattern separation, pattern completion, and new neuronal codes within a continuous CA3 map. Learn Mem 2007; 14(11): 745-57.
[] [PMID: 18007018]
Huang S, Ge X, Yu J, et al. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. FASEB J 2018; 32(1): 512-28.
[] [PMID: 28935818]
Moore TL, Bowley BGE, Pessina MA, et al. Mesenchymal derived exosomes enhance recovery of motor function in a monkey model of cortical injury. Restor Neurol Neurosci 2019; 37(4): 347-62.
[] [PMID: 31282441]
Williams AM, Dennahy IS, Bhatti UF, et al. Mesenchymal stem cell-derived exosomes provide neuroprotection and improve long-term neurologic outcomes in a swine model of traumatic brain injury and hemorrhagic shock. J Neurotrauma 2019; 36(1): 54-60.
[] [PMID: 29690826]
Al-Mufti F, Claassen J. Neurocritical care: status epilepticus review. Crit Care Clin 2014; 30(4): 751-64.
[] [PMID: 25257739]
Castro OW, Upadhya D, Kodali M, Shetty AK. Resveratrol for easing status epilepticus induced brain injury, inflammation, epileptogenesis, and cognitive and memory dysfunction-are we there yet? Front Neurol 2017; 8: 603.
[] [PMID: 29180982]
Upadhya D, Castro OW, Upadhya R, Shetty AK. Prospects of cannabidiol for easing status epilepticus-induced epileptogenesis and related comorbidities. Mol Neurobiol 2018; 55(8): 6956-64.
[] [PMID: 29372545]
Upadhya D, Hattiangady B, Castro OW, et al. Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration. Proc Natl Acad Sci USA 2019; 116(1): 287-96.
[] [PMID: 30559206]
Yuyama K, Sun H, Sakai S, et al. Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J Biol Chem 2014; 289(35): 24488-98.
[] [PMID: 25037226]
Cui GH, Wu J, Mou FF, et al. Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J 2018; 32(2): 654-68.
[] [PMID: 28970251]
Reza-Zaldivar EE, Hernández-Sapiéns MA, Gutiérrez-Mercado YK, et al. Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease. Neural Regen Res 2019; 14(9): 1626-34.
[] [PMID: 31089063]
Pusic AD, Pusic KM, Clayton BL, Kraig RP. IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. J Neuroimmunol 2014; 266(1-2): 12-23.
[] [PMID: 24275061]
Pusic AD, Kraig RP. Phasic treatment with interferon gamma stimulates release of exosomes that protect against spreading depression. J Interferon Cytokine Res 2015; 35(10): 795-807.
[] [PMID: 26083947]
Li Z, Liu F, He X, Yang X, Shan F, Feng J. Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia. Int Immunopharmacol 2019; 67: 268-80.
[] [PMID: 30572251]
Vogel A, Upadhya R, Shetty AK. Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders. EBioMedicine 2018; 38: 273-82.
[] [PMID: 30472088]

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