Generic placeholder image

Current Pharmaceutical Design


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

Mini-Review Article

Exosomes in Ischemic Stroke

Author(s): Saeideh Nozohouri, Bhuvaneshwar Vaidya* and Thomas J. Abbruscato*

Volume 26, Issue 42, 2020

Page: [5533 - 5545] Pages: 13

DOI: 10.2174/1381612826666200614180253

Price: $65


Ischemic stroke, a leading cause of mortality, results in severe neurological outcomes in the patients. Effective stroke therapies may significantly decrease the extent of injury. For this purpose, novel and efficient drug delivery strategies need to be developed. Among a myriad of therapeutic and drug delivery techniques, exosomes have shown promising results in ischemic stroke either by their intrinsic therapeutic characteristics, which can result in angiogenesis and neurogenesis or by acting as competent, biocompatible drug delivery vehicles to transport neurotherapeutic agents into the brain. In this review, we have discussed different methods of exosome isolation and cargo loading techniques, advantages and disadvantages of using exosomes as a drug delivery carrier and the therapeutic applications of exosomes with a focus on ischemic stroke therapy.

Keywords: Ischemic stroke, exosomes, brain drug delivery, stem cells, angiogenesis, neurogenesis.

« Previous
Albekairi TH, Vaidya B, Patel R, et al. Brain delivery of a potent opioid receptor agonist, biphalin during ischemic stroke: Role of Organic Anion Transporting Polypeptide (OATP). Pharmaceutics 2019; 11(9): 467.
[] [PMID: 31509975]
Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 2003; 4(5): 399-415.
[] [PMID: 12728267]
Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron 2010; 67(2): 181-98.
[] [PMID: 20670828]
Ginsberg MD. Current status of neuroprotection for cerebral ischemia: synoptic overview. Stroke 2009; 40(1): S111-4.
Sifat AE, Nozohouri S, Villalba H, et al. Prenatal electronic cigarette exposure decreases brain glucose utilization & worsens outcome in offspring hypoxic‐ischemic brain injury. J Neurochem 2019; 153(1): 63-79.
[PMID: 31883376]
Wang X, Mao X, Xie L, Sun F, Greenberg DA, Jin K. Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice. PLoS One 2012; 7(6)e38932
[] [PMID: 22723908]
Silva-Vargas V, Crouch EE, Doetsch F. Adult neural stem cells and their niche: a dynamic duo during homeostasis, regeneration, and aging. Curr Opin Neurobiol 2013; 23(6): 935-42.
[] [PMID: 24090877]
Ohab JJ, Fleming S, Blesch A, Carmichael ST. A neurovascular niche for neurogenesis after stroke. J Neurosci 2006; 26(50): 13007-16.
[] [PMID: 17167090]
Miyamoto N, Pham L-DD, Seo JH, Kim KW, Lo EH, Arai K. Crosstalk between cerebral endothelium and oligodendrocyte. Cell Mol Life Sci 2014; 71(6): 1055-66.
[] [PMID: 24132511]
Zhang ZG, Chopp M. Exosomes in stroke pathogenesis and therapy. J Clin Invest 2016; 126(4): 1190-7.
[] [PMID: 27035810]
Nozohouri S, Sifat AE, Vaidya B, Abbruscato TJ. Novel approaches for the delivery of therapeutics in ischemic stroke. Drug Discov Today 2020; 25(3): 535-51.
[] [PMID: 31978522]
Frühbeis C, Fröhlich D, Kuo WP, Krämer-Albers E-M. Extracellular vesicles as mediators of neuron-glia communication. Front Cell Neurosci 2013; 7: 182.
[] [PMID: 24194697]
György B, Hung ME, Breakefield XO, Leonard JN. Therapeutic applications of extracellular vesicles: clinical promise and open questions. Annu Rev Pharmacol Toxicol 2015; 55: 439-64.
[] [PMID: 25292428]
Wood MJ, O’Loughlin AJ, Samira L. Exosomes and the blood-brain barrier: implications for neurological diseases. Ther Deliv 2011; 2(9): 1095-9.
[] [PMID: 22833906]
Clayton A, Turkes A, Dewitt S, Steadman R, Mason MD, Hallett MB. Adhesion and signaling by B cell-derived exosomes: the role of integrins. FASEB J 2004; 18(9): 977-9.
[] [PMID: 15059973]
Chen J, Chopp M. Exosome therapy for stroke. Stroke 2018; 49(5): 1083-90.
[] [PMID: 29669873]
Edgar JR Jr. Q&A: What are exosomes, exactly? BMC Biol 2016; 14(1): 46.
[] [PMID: 27296830]
Saijo K, Glass CK. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol 2011; 11(11): 775-87.
[] [PMID: 22025055]
Verderio C, Muzio L, Turola E, et al. Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Ann Neurol 2012; 72(4): 610-24.
[] [PMID: 23109155]
Basso M, Pozzi S, Tortarolo M, et al. Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis. J Biol Chem 2013; 288(22): 15699-711.
[] [PMID: 23592792]
Hu G, Yao H, Chaudhuri A, et al. Exosome-mediated shuttling of microRNA-29 regulates HIV Tat and morphine-mediated neuronal dysfunction. Cell Death Dis 2012; 3(8)e381
Bobrie A, Colombo M, Raposo G, Théry C. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 2011; 12(12): 1659-68.
[] [PMID: 21645191]
Luga V, Zhang L, Viloria-Petit AM, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 2012; 151(7): 1542-56.
[] [PMID: 23260141]
Peinado H, Alečković M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 2012; 18(6): 883-91.
[] [PMID: 22635005]
EL Andaloussi S. Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013; 12(5): 347-57.
[] [PMID: 23584393]
Yeo RWY, Lai RC, Zhang B, et al. Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev 2013; 65(3): 336-41.
[] [PMID: 22780955]
Théry C, Duban L, Segura E, Véron P, Lantz O, Amigorena S. Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol 2002; 3(12): 1156-62.
[] [PMID: 12426563]
Goh WJ, Zou S, Ong WY, et al. Bioinspired cell-derived nanovesicles versus exosomes as drug delivery systems: a cost-effective alternative. Sci Rep 2017; 7(1): 14322.
[] [PMID: 29085024]
Agrawal AK, Aqil F, Jeyabalan J, et al. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine (Lond) 2017; 13(5): 1627-36.
[] [PMID: 28300659]
Aqil F, Jeyabalan J, Agrawal AK, et al. Exosomal delivery of berry anthocyanidins for the management of ovarian cancer. Food Funct 2017; 8(11): 4100-7.
[] [PMID: 28991298]
Morales-Kastresana A, Telford B, Musich TA, et al. Labeling extracellular vesicles for nanoscale flow cytometry. Sci Rep 2017; 7(1): 1878.
[] [PMID: 28500324]
Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 2017; 546(7659): 498-503.
[] [PMID: 28607485]
Stremersch S, Vandenbroucke RE, Van Wonterghem E, Hendrix A, De Smedt SC, Raemdonck K. Comparing exosome-like vesicles with liposomes for the functional cellular delivery of small RNAs. J Control Release 2016; 232: 51-61.
[] [PMID: 27072025]
Kumar L, Verma S, Vaidya B, Gupta V. Exosomes: natural carriers for siRNA delivery. Curr Pharm Des 2015; 21(31): 4556-65.
[] [PMID: 26486142]
Helwa I, Cai J, Drewry MD, et al. A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS One 2017; 12(1)e0170628
[] [PMID: 28114422]
Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics 2017; 7(3): 789-804.
[] [PMID: 28255367]
Bunggulawa EJ, Wang W, Yin T, et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnology 2018; 16(1): 81.
[] [PMID: 30326899]
Kang H, Kim J, Park J. Methods to isolate extracellular vesicles for diagnosis. Micro and Nano Systems Letters 2017; 5(1): 15.
Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery. Cancer Lett 2016; 371(1): 48-61.
[] [PMID: 26604130]
Arntz OJ, Pieters BC, Oliveira MC, et al. Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models. Mol Nutr Food Res 2015; 59(9): 1701-12.
[] [PMID: 26047123]
Akuma P, Okagu OD, Udenigwe CC. Naturally occurring exosome vesicles as potential delivery vehicle for bioactive compounds. Frontiers in Sustainable Food Systems 2019; 3: 23.
He M, Crow J, Roth M, Zeng Y, Godwin AK. Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology. Lab Chip 2014; 14(19): 3773-80.
[] [PMID: 25099143]
Vashisht M, Rani P, Onteru SK, Singh D. Curcumin encapsulated in milk exosomes resists human digestion and possesses enhanced intestinal permeability in vitro. Appl Biochem Biotechnol 2017; 183(3): 993-1007.
[] [PMID: 28466459]
Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J Control Release 2015; 205: 35-44.
[] [PMID: 25483424]
Liu C, Su C. Design strategies and application progress of therapeutic exosomes. Theranostics 2019; 9(4): 1015-28.
[] [PMID: 30867813]
Lin Y, Wu J, Gu W, et al. Exosome-liposome hybrid nanoparticles deliver CRISPR/Cas9 system in MSCs. Adv Sci (Weinh) 2018; 5(4)1700611
[] [PMID: 29721412]
Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine 2015; 10: 975-99.
[] [PMID: 25678787]
Sato YT, Umezaki K, Sawada S, et al. Engineering hybrid exosomes by membrane fusion with liposomes. Sci Rep 2016; 6: 21933.
[] [PMID: 26911358]
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]
Skog J, Würdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10(12): 1470-6.
[] [PMID: 19011622]
Tian T, Zhang H-X, He C-P, et al. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials 2018; 150: 137-49.
[] [PMID: 29040874]
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.
[] [PMID: 21915101]
Pan W, Zhang X, Liu X, et al. Exosomes derived from ischemic cerebral endothelial cells and neural progenitor cells enhance neurogenesis and angiogenesis Stroke 2016. 47(47): AWMP39
Pusic KM, Pusic AD, Kraig RP. Environmental enrichment stimulates immune cell secretion of exosomes that promote CNS myelination and may regulate inflammation. Cell Mol Neurobiol 2016; 36(3): 313-25.
[] [PMID: 26993508]
Morel L, Regan M, Higashimori H, et al. Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1. J Biol Chem 2013; 288(10): 7105-16.
[] [PMID: 23364798]
Clarkson AN, Overman JJ, Zhong S, Mueller R, Lynch G, Carmichael ST. AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke. J Neurosci 2011; 31(10): 3766-75.
[] [PMID: 21389231]
Fauré J, Lachenal G, Court M, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 2006; 31(4): 642-8.
[] [PMID: 16446100]
Krämer-Albers EM, Bretz N, Tenzer S, et al. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteomics Clin Appl 2007; 1(11): 1446-61.
[] [PMID: 21136642]
Wang S, Cesca F, Loers G, et al. Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J Neurosci 2011; 31(20): 7275-90.
[] [PMID: 21593312]
Lauritzen M, Dreier JP, Fabricius M, Hartings JA, Graf R, Strong AJ. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab 2011; 31(1): 17-35.
[] [PMID: 21045864]
Frühbeis C, Fröhlich D, Kuo WP, et al. Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol 2013; 11(7)e1001604
[] [PMID: 23874151]
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
[] [PMID: 25135971]
Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, Pegtel DM. Exosomes: Fit to deliver small RNA. Commun Integr Biol 2010; 3(5): 447-50.
[] [PMID: 21057637]
Katakowski M, Buller B, Zheng X, et al. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 2013; 335(1): 201-4.
[] [PMID: 23419525]
Suzuki E, Fujita D, Takahashi M, Oba S, Nishimatsu H. Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease. World J Stem Cells 2016; 8(9): 297-305.
[] [PMID: 27679686]
Sen CK. MicroRNAs as new maestro conducting the expanding symphony orchestra of regenerative and reparative medicine. MD: American Physiological Society Bethesda. Physiol Genomics 2011; 43(10): 517-20.
Liu FJ, Lim KY, Kaur P, et al. microRNAs involved in regulating spontaneous recovery in embolic stroke model. PLoS One 2013; 8(6)e66393
[] [PMID: 23823624]
Xin H, Li Y, Chopp M. Exosomes/miRNAs as mediating cell-based therapy of stroke. Front Cell Neurosci 2014; 8: 377.
[] [PMID: 25426026]
Rodrigues ML, Nimrichter L, Oliveira DL, Nosanchuk JD, Casadevall A. Vesicular trans-cell wall transport in fungi: a mechanism for the delivery of virulence-associated macromolecules? Lipid Insights 2008; 2: S1000.
Manuel GE, Johnson T, Liu D. Therapeutic angiogenesis of exosomes for ischemic stroke. Int J Physiol Pathophysiol Pharmacol 2017; 9(6): 188-91.
[PMID: 29348795]
Yamamoto S, Niida S, Azuma E, et al. Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes. Sci Rep 2015; 5: 8505.
[] [PMID: 25687367]
Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond) 2005; 109(3): 227-41.
[] [PMID: 16104843]
Zhang H, Wu J, Wu J, et al. Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice. J Nanobiotechnology 2019; 17(1): 29.
[] [PMID: 30782171]
Yang Y, Cai Y, Zhang Y, Liu J, Xu Z. Exosomes secreted by adipose-derived stem cells contribute to angiogenesis of brain microvascular endothelial cells following oxygen-glucose deprivation in vitro through microRNA-181b/TRPM7 axis. J Mol Neurosci 2018; 65(1): 74-83.
[] [PMID: 29705934]
Weis SM, Cheresh DA. Pathophysiological consequences of VEGF-induced vascular permeability. Nature 2005; 437(7058): 497-504.
[] [PMID: 16177780]
Zhang ZG, Zhang L, Jiang Q, et al. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 2000; 106(7): 829-38.
[] [PMID: 11018070]
Yang J, Zhang X, Chen X, Wang L, Yang G. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol Ther Nucleic Acids 2017; 7: 278-87.
[] [PMID: 28624203]
Yu YM, Gibbs KM, Davila J, et al. MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish. Eur J Neurosci 2011; 33(9): 1587-97.
[] [PMID: 21447094]
Xin H, Li Y, Buller B, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 2012; 30(7): 1556-64.
[] [PMID: 22605481]
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]
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]
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.
[] [PMID: 28232590]
Chen TS, Arslan F, Yin Y, et al. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. J Transl Med 2011; 9(1): 47.
[] [PMID: 21513579]
Roemeling-van Rhijn M, Reinders ME, Franquesa M, et al. Human allogeneic bone marrow and adipose tissue derived mesenchymal stromal cells induce CD8+ cytotoxic T cell reactivity. J Stem Cell Res Ther 2013; 3(6)
Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 2014; 32(3): 252-60.
[] [PMID: 24561556]
Lee J, Yoon Y, Lee S. Hypoxic preconditioning promotes the bioactivities of mesenchymal stem cells via the HIF-1α-GRP78-Akt axis. Int J Mol Sci 2017; 18(6): 1320.
Mathew SA, Chandravanshi B, Bhonde R. Hypoxia primed placental mesenchymal stem cells for wound healing. Life Sci 2017; 182: 85-92.
[] [PMID: 28625360]
Liu L, Gao J, Yuan Y, Chang Q, Liao Y, Lu F. Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF. Cell Biol Int 2013; 37(6): 551-60.
[] [PMID: 23505143]
Rasmussen JG, Frøbert O, Pilgaard L, et al. Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells. Cytotherapy 2011; 13(3): 318-28.
[] [PMID: 20795759]
Hu X, Yu SP, Fraser JL, et al. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg 2008; 135(4): 799-808.
[] [PMID: 18374759]
Wei L, Fraser JL, Lu Z-Y, 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.
[] [PMID: 22426403]
Oskowitz A, McFerrin H, Gutschow M, Carter ML, Pochampally R. Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic. Stem Cell Res (Amst) 2011; 6(3): 215-25.
[] [PMID: 21421339]
Hess DC, Borlongan CV. Cell-based therapy in ischemic stroke. Expert Rev Neurother 2008; 8(8): 1193-201.
[] [PMID: 18671663]
Chen J, Zhang ZG, Li Y, et al. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 2003; 92(6): 692-9.
[] [PMID: 12609969]
Wakabayashi K, Nagai A, Sheikh AM, et al. Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model. J Neurosci Res 2010; 88(5): 1017-25.
[PMID: 19885863]
Agrawal H, Shang H, Sattah AP, Yang N, Peirce SM, Katz AJ. Human adipose-derived stromal/stem cells demonstrate short-lived persistence after implantation in both an immunocompetent and an immunocompromised murine model. Stem Cell Res Ther 2014; 5(6): 142.
[] [PMID: 25523792]
Oh S-H, Choi C, Chang D-J, et al. Early neuroprotective effect with lack of long-term cell replacement effect on experimental stroke after intra-arterial transplantation of adipose-derived mesenchymal stromal cells. Cytotherapy 2015; 17(8): 1090-103.
[] [PMID: 26031742]
Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol 2009; 8(5): 491-500.
[] [PMID: 19375666]
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]
NCT03384433. Saadatnia M. Allogenic mesenchymal stem cell derived exosome in patients with acute ischemic stroke 2017. Available from:
Offner H, Vandenbark AA, Hurn PD. Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression. Neuroscience 2009; 158(3): 1098-111.
[] [PMID: 18597949]
Wong CH, Jenne CN, Lee W-Y, Léger C, Kubes P. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science 2011; 334(6052): 101-5.
[] [PMID: 21921158]
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]
Nozohouri S, Salehi R, Ghanbarzadeh S, Adibkia K, Hamishehkar H. A multilayer hollow nanocarrier for pulmonary co-drug delivery of methotrexate and doxorubicin in the form of dry powder inhalation formulation. Mater Sci Eng C 2019; 99: 752-61.
[] [PMID: 30889750]
Noorani B, Tabandeh F, Yazdian F, et al. Thin natural gelatin/chitosan nanofibrous scaffolds for retinal pigment epithelium cells. Int J Polymer Mater Polymer Biomater 2018; 67(12): 754-63.
ELA S. Mager I. Breakefield X, Wood M. Extracellular vesicles: 351 biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013; 352: 12.
Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med 2011; 9(1): 29.
[] [PMID: 21418664]
Kalani A, Chaturvedi P, Kamat PK, et al. Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury. Int J Biochem Cell Biol 2016; 79: 360-9.
[] [PMID: 27594413]
Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005; 57(6): 874-82.
[] [PMID: 15929052]
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.
[] [PMID: 24383518]
Wiklander OP, Nordin JZ, O’Loughlin A, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles 2015; 4(1): 26316.
[] [PMID: 25899407]
Liu XS, Chopp M, Zhang RL, Zhang ZG. MicroRNAs in cerebral ischemia-induced neurogenesis. J Neuropathol Exp Neurol 2013; 72(8): 718-22.
[] [PMID: 23860031]
Zhang R, Chopp M, Zhang ZG. Oligodendrogenesis after cerebral ischemia. Front Cell Neurosci 2013; 7: 201.
[] [PMID: 24194700]
Latchana N, Abrams ZB, Howard JH, et al. Plasma microRNA levels following resection of metastatic melanoma. Bioinform Biol Insights 2017; 111177932217694837
[] [PMID: 28469417]
Fatima F, Nawaz M. Stem cell-derived exosomes: roles in stromal remodeling, tumor progression, and cancer immunotherapy. Chin J Cancer 2015; 34(12): 541-53.
[] [PMID: 26369565]
El Bassit G, Patel RS, Carter G, et al. MALAT1 in human adipose stem cells modulates survival and alternative splicing of PKCδII in HT22 cells. Endocrinology 2017; 158(1): 183-95.
[PMID: 27841943]
Kang T, Jones TM, Naddell C, et al. Adipose‐derived stem cells induce angiogenesis via microvesicle transport of miRNA‐31. Stem Cells Transl Med 2016; 5(4): 440-50.
[] [PMID: 26933040]
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]
Geng W, Tang H, Luo S, et al. Exosomes from miRNA-126-modified ADSCs promotes functional recovery after stroke in rats by improving neurogenesis and suppressing microglia activation. Am J Transl Res 2019; 11(2): 780-92.
[PMID: 30899379]
Altmann P, Mildner M, Haider T, et al. Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia. F1000 Res 2014; 3: 131.
[] [PMID: 25383184]
Hayon Y, Dashevsky O, Shai E, Brill A, Varon D, Leker RR. Platelet microparticles induce angiogenesis and neurogenesis after cerebral ischemia. Curr Neurovasc Res 2012; 9(3): 185-92.
[] [PMID: 22621230]
Hayon Y, Shai E, Varon D, R, Leker R. The role of platelets and their microparticles in rehabilitation of ischemic brain tissue CNS Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS Neurological Disorders) 2012; 11(7): 921-5.
Sun X, Jung JH, Arvola O, et al. Stem cell-derived exosomes protect astrocyte cultures from in vitro ischemia and decrease injury as post-stroke intravenous therapy. Front Cell Neurosci 2019; 13: 394.
[] [PMID: 31551712]
Chen J, Ning R, Zacharek A, et al. MiR-126 Contributes to human umbilical cord blood cell-induced neurorestorative effects after stroke in type-2 diabetic mice. Stem Cells 2016; 34(1): 102-13.
[] [PMID: 26299579]
Zheng Y, He R, Wang P, Shi Y, Zhao L, Liang J. Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization. Biomater Sci 2019; 7(5): 2037-49.
[] [PMID: 30843911]
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.
[] [PMID: 31244932]
Tian Y, Zhu P, Liu S, et al. IL-4-polarized BV2 microglia cells promote angiogenesis by secreting exosomes. Adv Clin Exp Med 2019; 28(4): 421-30.
[] [PMID: 30684318]
Bian S, Zhang L, Duan L, Wang X, Min Y, Yu H. Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model. J Mol Med (Berl) 2014; 92(4): 387-97.
[] [PMID: 24337504]
Zhang Y, Chopp M, Liu XS, et al. Exosomes derived from mesenchymal stromal cells promote axonal growth of cortical neurons. Mol Neurobiol 2017; 54(4): 2659-73.
[] [PMID: 26993303]
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]
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]
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]
Deng M, Xiao H, Zhang H, et al. Mesenchymal stem cell-derived extracellular vesicles ameliorates hippocampal synaptic impairment after transient global ischemia. Front Cell Neurosci 2017; 11: 205.
[] [PMID: 28769765]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy