Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

The Therapeutic Applications of Exosomes in Different Types of Diseases: A Review

Author(s): Mohammadbagher Hosseini, Leila Roshangar, Sina Raeisi*, Kazem Ghahremanzadeh, Sohrab Negargar, Vahid Tarmahi, Vahid Hosseini, Mohammadreza Raeisi, Elnaz Rahimi and Zakiyeh Ebadi

Volume 21, Issue 2, 2021

Published on: 10 June, 2020

Page: [87 - 95] Pages: 9

DOI: 10.2174/1566524020666200610164743

Price: $65

conference banner
Abstract

Exosomes are nano-sized vesicles secreted by nearly all cells and have received massive attention recently. In addition to their roles in pathophysiological processes and diagnostic evaluations, recently, several studies have applied exosomes to design novel therapeutic applications. Exosomes can be derived from a variety of cells and tissues and based on the source, they can carry different native contents such as DNAs, non-coding small RNAs, mRNAs, and proteins. They can also be engineered by adding desirable agents including specific biomolecules or drugs. Both forms can be therapeutically used for delivering their cargoes to the target cells and desirably alter their functions. The present study aimed to provide a comprehensive review of the various studies which applied exosomes as a therapeutic tool in the treatment of different types of diseases including cancer, cardiovascular, neurologic, psychiatric, liver, and kidney diseases.

Keywords: Exosome, cancer, cardiovascular diseases, neurologic diseases, liver diseases, kidney diseases.

« Previous
[1]
Qin J, Xu Q. Functions and application of exosomes. Acta Pol Pharm 2014; 71(4): 537-43.
[PMID: 25272880]
[2]
Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 2012; 1820(7): 940-8.
[http://dx.doi.org/10.1016/j.bbagen.2012.03.017] [PMID: 22503788]
[3]
Ferguson SW, Nguyen J. Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity. J Control Release 2016; 228: 179-90.
[http://dx.doi.org/10.1016/j.jconrel.2016.02.037] [PMID: 26941033]
[4]
Trams EG, Lauter CJ, Salem JN, Heine U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochimica et Biophysica Acta (BBA)-. Biomembranes 1981; 645(1): 63-70.
[http://dx.doi.org/10.1016/0005-2736(81)90512-5]
[5]
Barile L, Vassalli G. Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol Ther 2017; 174: 63-78.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.020] [PMID: 28202367]
[6]
Masyuk AI, Masyuk TV, Larusso NF. Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases. J Hepatol 2013; 59(3): 621-5.
[http://dx.doi.org/10.1016/j.jhep.2013.03.028] [PMID: 23557871]
[7]
Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery. Cancer Lett 2016; 371(1): 48-61.
[http://dx.doi.org/10.1016/j.canlet.2015.10.020] [PMID: 26604130]
[8]
Bowers EC, Hassanin AAI, Ramos KS. In vitro models of exosome biology and toxicology: New frontiers in biomedical research. Toxicol In Vitro 2020.64104462
[http://dx.doi.org/10.1016/j.tiv.2019.02.016] [PMID: 31628015]
[9]
Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci 2018; 75(2): 193-208.
[http://dx.doi.org/10.1007/s00018-017-2595-9] [PMID: 28733901]
[10]
Edgar JR Jr. Q&A: What are exosomes, exactly? BMC Biol 2016; 14(1): 46.
[http://dx.doi.org/10.1186/s12915-016-0268-z] [PMID: 27296830]
[11]
Yu L-L, Zhu J, Liu J-X, et al. A comparison of traditional and novel methods for the separation of exosomes from human samples. BioMed Research International 2018.
[http://dx.doi.org/10.1155/2018/3634563]
[12]
Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics 2017; 7(3): 789-804.
[http://dx.doi.org/10.7150/thno.18133] [PMID: 28255367]
[13]
Liu C, Su C. Design strategies and application progress of therapeutic exosomes. Theranostics 2019; 9(4): 1015-28.
[http://dx.doi.org/10.7150/thno.30853] [PMID: 30867813]
[14]
Arslan F, Lai RC, Smeets MB, et al. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res (Amst) 2013; 10(3): 301-12.
[http://dx.doi.org/10.1016/j.scr.2013.01.002] [PMID: 23399448]
[15]
Li SP, Lin ZX, Jiang XY, Yu XY. Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools. Acta Pharmacol Sin 2018; 39(4): 542-51.
[http://dx.doi.org/10.1038/aps.2017.178] [PMID: 29417947]
[16]
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]
[17]
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]
[18]
Jang SC, Kim OY, Yoon CM, et al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano 2013; 7(9): 7698-710.
[http://dx.doi.org/10.1021/nn402232g] [PMID: 24004438]
[19]
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.
[http://dx.doi.org/10.1096/fj.03-1094fje] [PMID: 15059973]
[20]
van Balkom BW, Pisitkun T, Verhaar MC, Knepper MA. Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases. Kidney Int 2011; 80(11): 1138-45.
[http://dx.doi.org/10.1038/ki.2011.292] [PMID: 21881557]
[21]
Inamdar S, Nitiyanandan R, Rege K. Emerging applications of exosomes in cancer therapeutics and diagnostics. Bioeng Transl Med 2017; 2(1): 70-80.
[http://dx.doi.org/10.1002/btm2.10059] [PMID: 28529978]
[22]
Lv L-H, Wan Y-L, Lin Y, et al. Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro. J Biol Chem 2012; 287(19): 15874-85.
[http://dx.doi.org/10.1074/jbc.M112.340588] [PMID: 22396543]
[23]
Rao Q, Zuo B, Lu Z, et al. Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro. Hepatology 2016; 64(2): 456-72.
[http://dx.doi.org/10.1002/hep.28549] [PMID: 26990897]
[24]
Escudier B, Dorval T, Chaput N, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med 2005; 3(1): 10.
[http://dx.doi.org/10.1186/1479-5876-3-10] [PMID: 15740633]
[25]
Lässer C. Exosomes in diagnostic and therapeutic applications: biomarker, vaccine and RNA interference delivery vehicle. Expert Opin Biol Ther 2015; 15(1): 103-17.
[http://dx.doi.org/10.1517/14712598.2015.977250] [PMID: 25363342]
[26]
Raghavan V. Role of exosomes in psychiatric disorders. Asian J Psychiatr 2017; 28: 78-9.
[http://dx.doi.org/10.1016/j.ajp.2017.03.032] [PMID: 28784402]
[27]
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]
[28]
Yang T, Martin P, Fogarty B, et al. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res 2015; 32(6): 2003-14.
[http://dx.doi.org/10.1007/s11095-014-1593-y] [PMID: 25609010]
[29]
Fonsato V, Collino F, Herrera MB, et al. Human liver stem cell-derived microvesicles inhibit hepatoma growth in SCID mice by delivering antitumor microRNAs. Stem Cells 2012; 30(9): 1985-98.
[http://dx.doi.org/10.1002/stem.1161] [PMID: 22736596]
[30]
Zhang Z, Dombroski JA, King MR. Engineering of Exosomes to Target Cancer Metastasis. Cell Mol Bioeng 2019; 13(1): 1-16.
[http://dx.doi.org/10.1007/s12195-019-00607-x] [PMID: 32030104]
[31]
Viaud S, Terme M, Flament C, et al. Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha. PLoS One 2009; 4(3)e4942
[http://dx.doi.org/10.1371/journal.pone.0004942] [PMID: 19319200]
[32]
Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 2017; 546(7659): 498-503.
[http://dx.doi.org/10.1038/nature22341] [PMID: 28607485]
[33]
Herrera MB, Fonsato V, Gatti S, et al. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med 2010; 14(6B): 1605-18.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00860.x] [PMID: 19650833]
[34]
Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 2013; 22(6): 845-54.
[http://dx.doi.org/10.1089/scd.2012.0395] [PMID: 23002959]
[35]
Tan CY, Lai RC, Wong W, Dan YY, Lim S-K, Ho HK. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther 2014; 5(3): 76.
[http://dx.doi.org/10.1186/scrt465] [PMID: 24915963]
[36]
Pan Q, Ramakrishnaiah V, Henry S, et al. Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference (RNAi). Gut 2012; 61(9): 1330-9.
[http://dx.doi.org/10.1136/gutjnl-2011-300449] [PMID: 22198713]
[37]
Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 2015; 207: 18-30.
[http://dx.doi.org/10.1016/j.jconrel.2015.03.033] [PMID: 25836593]
[38]
Kalani A, Tyagi A, Tyagi N. Exosomes: mediators of neurodegeneration, neuroprotection and therapeutics. Mol Neurobiol 2014; 49(1): 590-600.
[http://dx.doi.org/10.1007/s12035-013-8544-1] [PMID: 23999871]
[39]
Mehdizadeh A, Barzegar M, Negargar S, Yahyavi A, Raeisi S. The current and emerging therapeutic approaches in drug-resistant epilepsy management. Acta Neurol Belg 2019; 119(2): 155-62.
[http://dx.doi.org/10.1007/s13760-019-01120-8] [PMID: 30868468]
[40]
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29(4): 341-5.
[http://dx.doi.org/10.1038/nbt.1807] [PMID: 21423189]
[41]
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]
[42]
Lopez-Verrilli MA, Picou F, Court FA. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 2013; 61(11): 1795-806.
[http://dx.doi.org/10.1002/glia.22558] [PMID: 24038411]
[43]
Jia L, Chopp M, Wang L, Lu X, Szalad A, Zhang ZG. Exosomes derived from high-glucose-stimulated Schwann cells promote development of diabetic peripheral neuropathy. FASEB J 2018; 32(12)fj201800597R
[http://dx.doi.org/10.1096/fj.201800597R] [PMID: 29932869]
[44]
Ranganathan M, Rahman M, Ganesh S, et al. Analysis of Circulating Exosomes Reveals a Peripheral Signature of Astrocytic Pathology in Schizophrenia. bioRxiv 2020.
[45]
Ceylan D, Tufekci KU, Keskinoglu P, Genc S, Özerdem A. Circulating exosomal microRNAs in bipolar disorder. J Affect Disord 2020; 262: 99-107.
[http://dx.doi.org/10.1016/j.jad.2019.10.038] [PMID: 31726266]
[46]
Amoah SK, Rodriguez BA, Logothetis CN, et al. Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics. Neuropsychopharmacology 2020; 45(4): 656-65.
[http://dx.doi.org/10.1038/s41386-019-0579-1] [PMID: 31775160]
[47]
Poe AJ, Knowlton AA. Exosomes as agents of change in the cardiovascular system. J Mol Cell Cardiol 2017; 111: 40-50.
[http://dx.doi.org/10.1016/j.yjmcc.2017.08.002] [PMID: 28782514]
[48]
Wang X, Gu H, Huang W, et al. Hsp20-mediated activation of exosome biogenesis in cardiomyocytes improves cardiac function and angiogenesis in diabetic mice. Diabetes 2016; 65(10): 3111-28.
[http://dx.doi.org/10.2337/db15-1563] [PMID: 27284111]
[49]
Vicencio JM, Yellon DM, Sivaraman V, et al. Plasma exosomes protect the myocardium from ischemia-reperfusion injury. J Am Coll Cardiol 2015; 65(15): 1525-36.
[http://dx.doi.org/10.1016/j.jacc.2015.02.026] [PMID: 25881934]
[50]
Gray WD, French KM, Ghosh-Choudhary S, et al. Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circ Res 2015; 116(2): 255-63.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.304360] [PMID: 25344555]
[51]
Chen L, Wang Y, Pan Y, et al. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem Biophys Res Commun 2013; 431(3): 566-71.
[http://dx.doi.org/10.1016/j.bbrc.2013.01.015] [PMID: 23318173]
[52]
Khan M, Nickoloff E, Abramova T, et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction Circul Res 2015.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.305990]
[53]
Sahoo S, Klychko E, Thorne T, et al. Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res 2011; 109(7): 724-8.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.253286] [PMID: 21835908]
[54]
Kawamoto A, Iwasaki H, Kusano K, et al. CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 2006; 114(20): 2163-9.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.644518] [PMID: 17075009]
[55]
Gallet R, Dawkins J, Valle J, et al. Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction. Eur Heart J 2017; 38(3): 201-11.
[PMID: 28158410]
[56]
Teng X, Chen L, Chen W, Yang J, Yang Z, Shen Z. Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation. Cell Physiol Biochem 2015; 37(6): 2415-24.
[http://dx.doi.org/10.1159/000438594] [PMID: 26646808]
[57]
Zhang Z, Yang J, Yan W, Li Y, Shen Z, Asahara T. Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair. J Am Heart Assoc 2016; 5(1)e002856
[http://dx.doi.org/10.1161/JAHA.115.002856] [PMID: 26811168]
[58]
Hergenreider E, Heydt S, Tréguer K, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 2012; 14(3): 249-56.
[http://dx.doi.org/10.1038/ncb2441] [PMID: 22327366]
[59]
Davidson SM, Yellon DM. Exosomes and cardioprotection–A critical analysis. Mol Aspects Med 2017.
[PMID: 29122678]
[60]
Emanueli C, Shearn AI, Angelini GD, Sahoo S. Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vascul Pharmacol 2015; 71: 24-30.
[http://dx.doi.org/10.1016/j.vph.2015.02.008] [PMID: 25869502]
[61]
Huang L, Ma W, Ma Y, Feng D, Chen H, Cai B. Exosomes in mesenchymal stem cells, a new therapeutic strategy for cardiovascular diseases? Int J Biol Sci 2015; 11(2): 238-45.
[http://dx.doi.org/10.7150/ijbs.10725] [PMID: 25632267]
[62]
Zhou Y, Xu H, Xu W, et al. Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Ther 2013; 4(2): 34.
[http://dx.doi.org/10.1186/scrt194] [PMID: 23618405]
[63]
Zou X, Zhang G, Cheng Z, et al. Microvesicles derived from human Wharton’s Jelly mesenchymal stromal cells ameliorate renal ischemia-reperfusion injury in rats by suppressing CX3CL1. Stem Cell Res Ther 2014; 5(2): 40.
[http://dx.doi.org/10.1186/scrt428] [PMID: 24646750]
[64]
Bruno S, Grange C, Deregibus MC, et al. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol 2009; 20(5): 1053-67.
[http://dx.doi.org/10.1681/ASN.2008070798] [PMID: 19389847]
[65]
He J, Wang Y, Sun S, et al. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology (Carlton) 2012; 17(5): 493-500.
[http://dx.doi.org/10.1111/j.1440-1797.2012.01589.x] [PMID: 22369283]
[66]
Reis LA, Borges FT, Simões MJ, Borges AA, Sinigaglia-Coimbra R, Schor N. Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats. PLoS One 2012; 7(9)e44092
[http://dx.doi.org/10.1371/journal.pone.0044092] [PMID: 22970165]

Rights & Permissions Print Cite
Article Metrics
61
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy