Download pdf - Exosomes, Extracellular Vesicles A Technology Review...Exosomes, Extracellular Vesicles: Topic Introduction • The focus of this report is on Exosomes, extracellular vesicles and

Exosomes,ExtracellularVesiclesATechnologyReview

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Author,DataCollectionDate,Notes

•  TheAuthor–  GaryM.Oosta,holdsaPh.D.inBiophysicsfromMassachusettsInstituteofTechnologyandaB.A.inChemistryfromE.

Mich.Univ.Hehas25yearsofindustrialresearchexperienceinvarioustechnologyareasincludingmedicaldiagnostics,thin-layercoating,bio-effectsofelectromagneticradiation,andbloodcoagulation.Dr.Oostahasauthoredmorethan20technicalpublicationsandisaninventoron77patentsworldwide.Inaddition,hehasmanagedresearchgroupsthatwereresponsibleformanyotherpatentedinnovations.Dr.Oostahasalong-standinginterestinusingpatentsandpublicationsasstrategictechnologyindicatorsforfuturetechnologyselectionandnewproductdevelopment.

–  E-mail:[email protected]

•  DataforthisreportwascollectedonMarch7,2018.–  Annualvaluesfor2018wereextrapolatedfrom2014-2017data.–  FouryearCAGR’suseddatafrom2014and2017.

•  Thispresentationisnotmanagement,legaloraccountingadvice.–  Whilewebelievethattheresultswereaccurateatthetimeofpublication,theresultsareprovidedwithoutwarranty.

•  ©SelectBiosciences.2018.Allrightsreserved.

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Exosomes,ExtracellularVesicles&OtherParticles:TopicIntroduction&theAnalysisProcessSummary

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Exosomes,ExtracellularVesicles:TopicIntroduction

•  ThefocusofthisreportisonExosomes,extracellularvesiclesandotherbodiesthatmaycontaininformationfromacell.–  Ourreportpresentsasnapshotoffieldthatwebelieveischangingfocus.–  WeframethedatainthecontextofthecurrentstateofExosomesandECV’s

•  Toprepareourreport,weutilizedafourstepprocess.1.  WeIDENTIFIEDtechnicaltrendsinabroadlyselectedliteraturedatabaseby

categorizingandsegmentingthedatabaseintoproducts,productfeatures,materials,processesandmethodstoformamodel.

2.  WeMEASUREDeachtrendprogresswithuniqueyardsticks.3.  WeVISUALIZEDthetrendssothatyoucanseethemforyourself.4.  WePRESENTEDourconclusionsconcisely.

•  Inthisreport,weanalyzed47,643publicationswhichenblocrepresenttheentirebodyofliteratureoftheExosomeandECVspace.

•  Bycastingthetechnicalliteratureintotechnologysegments,disease-relatedsegmentsandmarket-relatedsegments,webelievethatwecancreateanunbiasedviewacrossthelandscapeasameanstoidentifymarketsegments,trends,andimportantniches.

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Usingkeywordstocasttechnicalpublicationsintomarketfocuses,products,productfeatures,materials,processesandmethodsprovidesauniquelyaccuratepictureofhowthetechnologyisdeveloping.Suchatechnologicalpicturealsocontainsuniqueinsightsintothestructureofthemarketitself.

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Exosomes&EVsarearapidlyexpandingarea.TheExosomespaceasrepresentedbyourdatabaseof47,643PubMedtitlesandabstractsisarapidlyexpandingarea..From2014to2017,theCAGRwas9.3%,asignificantgrowthrateeveninbiotech.Weusethisvalue(9.3%)asabenchmarktojudgewhetheraspecificsegmentsisgrowingfaster,sloweroratthenormforthedatabase.

ComprehensiveStudyDatabase

JournalsintheExosome,ECVDatabase

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TheDatabasecontains3733journals,andtheexpectedjournalstopthelist.OnewaytovalidatetheutilityofthedatabaseistobesurethatitcontainsjournalsthatcovertheExosome&ECVarea.Thevalidationisbyexperienceinthearea.

Rank JournalNumber

ofPapers

Rank JournalNumber

ofPapers

Rank JournalNumber

ofPapers

Rank JournalNumber

ofPapers

1 J.BIOL.CHEM. 1911 26 J.NEUROCHEM. 191 51 EUR.J.IMMUNOL. 127 76 J.CLIN.INVEST. 962 PLOSONE 1169 27 BIOCHEMISTRY 189 52 METH.ENZYMOL. 126 77 FEBSJ. 953 J.CELLBIOL. 823 28 NATCOMMUN 186 53 SCIENCE 121 78 J.CELL.MOL.MED. 934 PROC.NATL.ACAD.SCI.U.S.A. 746 29 CELLTISSUERES. 185 54 J.THROMB.HAEMOST. 120 79 J.EXP.MED. 935 J.CELL.SCI. 702 30 JEXTRACELLVESICLES 180 55 AM.J.PATHOL. 119 80 J.GEN.VIROL. 936 MOL.BIOL.CELL 699 31 NATURE 178 56 BIOCONJUG.CHEM. 118 81 BIOPHYS.J. 917 TRAFFIC 560 32 THROMB.HAEMOST. 170 57 NUCLEICACIDSRES. 118 82 J.LEUKOC.BIOL. 918 J.VIROL. 553 33 J.CELL.PHYSIOL. 165 58 MOL.PHARM. 116 83 TRENDSCELLBIOL. 919 BIOCHIM.BIOPHYS.ACTA 514 34 CANCERRES. 162 59 J.CELL.BIOCHEM. 115 84 CELLREP 9010 SCIREP 482 35 CURR.BIOL. 162 60 ACSNANO 111 85 J.HISTOCHEM.CYTOCHEM. 8711 J.IMMUNOL. 475 36 INFECT.IMMUN. 162 61 CIRC.RES. 111 86 ONCOL.REP. 8712 BIOCHEM.BIOPHYS.RES.COMMUN. 419 37 PLOSPATHOG. 162 62 NEUROSCIENCE 111 87 SEMIN.CELLDEV.BIOL. 8713 METHODSMOL.BIOL. 333 38 MOL.CELL.BIOL. 158 63 ENDOCRINOLOGY 110 88 VACCINE 8714 J.NEUROSCI. 322 39 VIROLOGY 156 64 HUM.MOL.GENET. 110 89 CANCERLETT. 8615 ONCOTARGET 293 40 NAT.CELLBIOL. 154 65 INTJPHARM 104 90 PROTEOMICS 8616 BIOCHEM.J. 289 41 AUTOPHAGY 153 66 ONCOGENE 104 91 DEV.BIOL. 8517 EXP.CELLRES. 283 42 AM.J.PHYSIOL. 149 67 CELL.MOL.LIFESCI. 103 92 AM.J.PHYSIOL.RENALPHYSIOL. 8418 EMBOJ. 276 43 INTJMOLSCI 146 68 DEVELOPMENT 101 93 ANTICANCERRES. 8419 BLOOD 275 44 ADV.EXP.MED.BIOL. 140 69 MOL.CELL 101 94 APOPTOSIS 8320 JCONTROLRELEASE 260 45 BRAINRES. 140 70 AM.J.PHYSIOL.,CELLPHYSIOL. 100 95 ANN.N.Y.ACAD.SCI. 8221 BIOMATERIALS 242 46 CELL.MICROBIOL. 140 71 INT.J.CANCER 100 96 J.LIPIDRES. 8222 CELL 223 47 FASEBJ. 132 72 ARTERIOSCLER.THROMB.VASC.BIOL. 99 97 BIOL.REPROD. 8123 EUR.J.CELLBIOL. 213 48 BIOCHEM.SOC.TRANS. 131 73 CURR.OPIN.CELLBIOL. 97 98 TRANSFUSION 8124 FEBSLETT. 200 49 DEV.CELL 130 74 HEPATOLOGY 97 99 BIOCHEM.PHARMACOL. 7825 THROMB.RES. 192 50 FRONTIMMUNOL 129 75 J.PHYSIOL.(LOND.) 97 100 KIDNEYINT. 78

Therewere3581uniquejournaltitlesinourdatabase.

RegionsintheExosomes&ECVDatabase

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PubMedprovidesaddressinformationforeachauthor.Addressescanbeminedtoidentifythelocation(countryandregionoftheworld)wheretheworkisbeingdone.Clearly,theUS,AsiaandEuropearethedominantareas,andeachonecontributesasimilarnumberofauthorlocations.Thesameanalysiscanalsobedonebycountry.

RegionPercentofTotal

EUROPE 36.2%USA-COUNTRY 28.8%ASIA 27.1%NORTHAMERICA 3.3%AUSTRALIA 2.6%CENTRAL,SOUTHAMERICA 1.3%AFRICA 0.52%MIDDLEEAST 0.15%CARIBBEAN 0.0378%POLYNESIA,OCEANIA 0.0007%

Exosome-RelatedTerms

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Weextractedandcountedthetermsrelatedtoexosomesbyyear.Fromthatdata,wecalculated4-yearCAGR’sandplottedthetemporaltends.Greenindicatesthattheareaiscontracting.Redindicatesgrowth.Thetermsextracellularvesicle,exosomeandnanovesicleshowstronggrowth.

Exosome-RelatedTerms 4-YrCAGRCELL-DERIVEDMICROPARTICLE -4.62%CIRCULATINGMICROPARTICLE 0.00%APOPTOTICBODY_APOTOTICBLEB 2.20%CELL-DERIVEDMICROPARTICLE -4.62%CELL-DERIVEDVESICLEORPARTICLEORMICROPARTICLE 8.93%ECTOSOME_ECTOSOMES 18.92%ENDOSOME,(S),(AL),(IC,-X -1.67%EXOSOME,(S),(AL),-X 25.28%LYSOSOME 3.20%AUTOPHAGOSOME 10.14%ENDOLYSOSOME -8.34%LIPOSOME 12.91%LYSOSOME 1.97%PHAGOSOME 5.74%EXTRACELLULARVESICLE 42.35%MULTIVESICULARBODIES(MVBs) -15.91%SECRETORYVESICLES(FROMGOLGI) 5.38%SYNAPTICVESICLES -6.60%MICROVESICLE 15.62%NANOVESICLE 22.81%PLATELET_DERIVEDMICROPARTICLE 2.20%

TrendsinMainExosome-RelatedTerms

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The4-yearCAGR’sindicatedwhichareasareshowingcurrentgrowth.Temporalplotsofauthorsusesofexosome-relatedtermsareasimilarlyinstructive.ThesearetheMAINterms.Noticethatmanytermsarenearlyburiedinthenoiseatthebottomofthechar.t

TrendsinSmallerExosome-RelatedTerms

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The4-yearCAGR’sindicatedwhichareasareshowingcurrentgrowth.Temporalplotsofauthorsusesofexosome-relatedtermsareasimilarlyinstructive.ThesearetheSMALLERterms.Noticethatmanytermsarenearlyburiedinthenoiseatthebottomofthechar.t

SampleTypesintheDB

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Plasma,bloodandserumaethedominantsampletypesintheExosomedatabase.Urine(blue)isemergingasis“biofluid”(brown).Manysamplestypesappeartounexplored.

LargerCommonTechnologies

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CommontechnologymethodssupportdevelopmentsinExosomesandECV’s.CAGR’srangefrom6%to25+%

fluorescence

antibody

westernblot

spectrometry

massspec

ultra-centrifugecentrifuge

chromatography

SmallerTechnologiesSupportingExosome&EVs

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ManysmallersizedbutcommontechnologiesarebeingusedinExosomeandECVdevelopments.

PrecipitationAFMmanufacturing

Densitygradientcentrifugation

NoticeScaleChange

ImagingMethodsinExosomes&EVs

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Thegeneraltermsinimagingarethemostcommon.

LiquidBiopsy:ANewerAssayTerm

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Whiletraditionalassaymethodsaregrowingintheexosome&ECVarea,theideaofaliquidbiopsyisexplodingontothescene.

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StemCellsinExosomesThekeywordsstemcellsandmesenchymalstemcellsaremostimportantinexosomeresearchwith4-yrCAGR’sof30%and37%,respectively.Otherstemcelltypesarementionedlessfrequently,butthetrendinnearlyallcasesisupward.

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CellSignaling:LargeAreainExosomesCellsignalingisalarge,activeareainexosomeresearch.Thekeyword“signalingpathway”isaspecificgrowtharea.Otherthemesthatwetrackremainfairlysmall.

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Communication:AnExosomeFunctionExosomesarethoughttoparticipateincell-to-cellcommunication.Theresearchagendaisdescribedinthetableofadjacentwords.

CommunicationKeyword %TotalINTERCELLULARCOMMUNICATION 750CELL-TO-CELLCOMMUNICATION 285CELL-CELLCOMMUNICATION 182CELLCOMMUNICATION 80CELLULARCOMMUNICATION 61MEDIATEINTERCELLULARCOMMUNICATION 60INTERCELLULARCOMMUNICATIONS 46VESICLESINTERCELLULARCOMMUNICATION 22EXOSOME-MEDIATEDINTERCELLULARCOMMUNICATION 21INTRACELLULARCOMMUNICATION 16MEDIATECELL-CELLCOMMUNICATION 15JUNCTIONALINTERCELLULARCOMMUNICATION 15INTER-CELLULARCOMMUNICATION 14CELLΓÇôCELLCOMMUNICATION 12MEDIATECOMMUNICATION 12EXOSOMESINTERCELLULARCOMMUNICATION 11FACILITATEINTERCELLULARCOMMUNICATION 11CELL-CELLCOMMUNICATIONS 10MEDIATECELL-TO-CELLCOMMUNICATION 10NEURONALCOMMUNICATION 10CELLULARCOMMUNICATIONS 9MEDIATINGINTERCELLULARCOMMUNICATION 9EXTRACELLULARCOMMUNICATION 8INCLUDINGINTERCELLULARCOMMUNICATION 8JUNCTIONINTERCELLULARCOMMUNICATION 8EXTRACELLULARRNACOMMUNICATION 8

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InteractionsinExosomesInteractionsisakeythemeinexosomeresearch.Thetableshowsthemostfrequent30wordsmodifyingthewordinteraction(ofmorethan3300separate,non-trivialkeywordpairs)inourexosomedatabase.

1.  DIRECTINTERACTION2.  PROTEIN-PROTEININTERACTION3.  ELECTROSTATICINTERACTION4.  SPECIFICINTERACTION5.  CELL-CELLINTERACTION6.  CELLULARINTERACTION7.  PROTEININTERACTION8.  PHYSICALINTERACTION9.  MOLECULARINTERACTION10.  FUNCTIONALINTERACTION11.  HOST-PATHOGENINTERACTION12.  MEMBRANEINTERACTION13.  HYDROPHOBICINTERACTION14.  COMPLEXINTERACTION15.  GENETICINTERACTION16.  DYNAMICINTERACTION17.  CELLINTERACTION18.  POTENTIALINTERACTION19.  CELL-MATRIXINTERACTION20.  RECEPTORINTERACTION21.  IONICINTERACTION22.  LIGAND-RECEPTORINTERACTION23.  TRANSIENTINTERACTION24.  STRONGINTERACTION25.  LIPIDINTERACTION26.  INTRAMOLECULARINTERACTION27.  PROTEIN-LIPIDINTERACTION28.  HIGHAFFINITYINTERACTION29.  MEDIATEINTERACTION30.  RECEPTOR-LIGANDINTERACTION

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Biomarkers:RapidlyGrowinginExosomesBiomarkersareasignificantthemeinexosome,ECVresearchandhasa4-yrCAGRof30%.

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MicroRNAsAssociatedwithExosomes,EVs:1NaminginmicroRNAsisfairlystandard.WeextractedandstandardizedMIRnamesfromourexosomedatabaseandassociatedtheMIRnameswithselectedparticletypes.Wesortedthedatabythefrequencyofassociationwithexosomes.Thefrequencysuggestsstrongconnectiontocancerresearchforexosomesandextracellularvesicles,butnotfortheotherparticlesexamined.Thismaybeatruefindingoritmightbedrivenbyourselectionofmainsearchstrategies.

MicroRNACELL-DERIVED

MICROPARTICLEENDOSOME EXOSOME

EXTRACELLULARVESICLE

LYSOSOME MicroRNACELL-DERIVED



LYSOSOME

MIR-21 5 1 126 36 2 MIR-375 0 2 15 7 2MIR-146 0 1 50 19 0 MIR-486 0 0 15 5 0MIR-155 1 2 49 18 0 MIR-9 1 0 15 1 0LET-7 0 6 45 15 2 MIR-106 0 0 14 4 0MIR-29 0 2 34 10 2 MIR-181 0 0 14 2 0MIR-17 0 0 32 5 0 MIR-20 0 0 14 7 0MIR-223 0 0 32 14 0 MIR-206 0 0 14 5 0MIR-126 4 0 31 13 0 MIR-199 0 1 13 7 1MIR-200 0 2 31 12 2 MIR-320 0 1 13 10 0MIR-30 0 1 29 17 0 MIR-214 0 0 12 3 0MIR-221 0 1 27 6 0 MIR-24 0 0 12 5 0MIR-23 0 0 27 10 0 MIR-100 0 0 11 2 0MIR-122 0 1 25 13 0 MIR-135 0 3 11 1 0MIR-125 1 1 25 15 0 MIR-205 0 0 11 5 0MIR-133 0 1 24 3 0 MIR-25 0 0 11 5 0MIR-210 1 0 24 13 0 MIR-26 1 0 11 5 0MIR-16 0 0 23 9 0 MIR-7 0 0 11 2 0MIR-15 0 0 20 4 0 MIR-130 0 0 10 3 0MIR-92 1 2 20 9 0 MIR-132 0 0 10 3 0MIR-124 0 2 19 1 2 MIR-141 0 0 10 2 0MIR-150 0 0 19 10 0 MIR-148 0 1 10 3 2MIR-222 1 0 19 8 0 MIR-143 1 0 9 9 0MIR-27 0 1 19 9 0 MIR-192 0 0 9 3 0MIR-145 0 1 18 10 0 MIR-128 0 1 8 2 0MIR-10 0 0 17 5 2 MIR-18 0 1 8 2 2MIR-1246 0 0 17 2 0 MIR-191 0 0 8 3 0MIR-19 1 1 17 7 0 MIR-195 0 0 8 3 0MIR-451 1 2 17 12 0 MIR-196 0 0 8 3 0MIR-34 0 1 16 6 0 MIR-208 0 0 8 2 0MIR-1 0 0 15 4 0 MIR-378 0 1 8 5 0

Page1ResultsarepresentedindescendingorderofthenumberofpapersincommonforexosomesandMIR.Intotaltherewere354MIRnamesfound.

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MicroRNAsAssociatedwithExosomes,EVs:2NaminginmicroRNAsisfairlystandard.WeextractedandstandardizedMIRnamesfromourexosomedatabaseandassociatedtheMIRnameswithselectedparticletypes.Wesortedthedatabythefrequencyofassociationwithexosomes.Thefrequencysuggestsstrongconnectiontocancerresearchforexosomesandextracellularvesicles,butnotfortheotherparticlesexamined.Thismaybeatruefindingoritmightbedrivenbyourselectionofmainsearchstrategies.

MicroRNACELL-DERIVED



LYSOSOME MicroRNACELL-DERIVED



LYSOSOME

MIR-101 0 0 7 3 0 MIR-365 0 0 4 1 0MIR-1290 0 0 7 3 0 MIR-499 0 0 4 0 0MIR-142 0 1 7 7 0 MIR-574 0 1 4 1 0MIR-203 0 1 7 1 0 MIR-720 0 0 4 3 0MIR-204 0 0 7 6 0 MIR-96 0 0 4 1 0MIR-342 0 0 7 0 0 MIR-103 0 0 3 5 0MIR-483 0 0 7 3 0 MIR-107 0 0 3 0 0MIR-93 0 0 7 3 0 MIR-1228 0 0 3 0 0MIR-140 0 0 6 0 0 MIR-127 0 0 3 1 0MIR-22 0 1 6 1 0 MIR-134 0 0 3 1 0MIR-31 0 0 6 2 0 MIR-182 0 0 3 0 0LET-7G 0 0 5 0 0 MIR-212 0 0 3 2 0MIR-149 0 0 5 1 0 MIR-219 0 0 3 0 0MIR-183 0 0 5 1 0 MIR-296 0 0 3 3 0MIR-197 0 0 5 1 0 MIR-33 0 1 3 0 0MIR-301 0 0 5 2 0 MIR-335 0 0 3 2 0MIR-339 0 0 5 0 0 MIR-340 0 0 3 1 0MIR-379 0 0 5 2 0 MIR-361 0 0 3 0 0MIR-409 0 0 5 1 0 MIR-3613 0 1 3 1 0MIR-494 0 1 5 0 2 MIR-371 0 0 3 1 0MIR-638 0 0 5 1 0 MIR-372 0 0 3 0 0LET-7F 0 1 4 5 0 MIR-373 0 0 3 0 0LET-7I 0 0 4 0 0 MIR-378I 0 0 3 1 0MIR-139 0 0 4 1 0 MIR-39 0 0 3 3 0MIR-185 0 0 4 3 0 MIR-424 0 0 3 0 0MIR-193 0 0 4 1 0 MIR-425 0 0 3 1 0MIR-215 0 0 4 2 0 MIR-4454 0 1 3 1 0MIR-218 0 0 4 2 0 MIR-520 0 0 3 0 0MIR-224 0 0 4 0 0 MIR-548 0 0 3 0 0MIR-302 0 0 4 2 0 MIR-584 0 0 3 0 0

ResultsarepresentedindescendingorderofthenumberofpapersincommonforexosomesandMIR.Intotaltherewere354MIRnamesfound.Page2

FewClinicalTrialsinExosomes,EVssofar

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AsExosomesandECV’smovefromresearchtotreatmentintheclinic,moreclinicaltrialscanbeexpected.Thegrowthoftheclinicaltrialkeyword(bluetriangles,4-YrCAGRof26%)andtherelativelysmallnumbersofpaperstalkingofspecificclinicaltrialphasesindicatesthattheprocessisstillinitsinfancy.Diagnosticapplicationsprobablywouldnottaketheclinicaltrialspathandareprobablynotrepresentedinthischart.

CancerintheExosomeDatabase

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CancerisalargeandpersistentthemeinExosomes.Witha4-yearCAGRof13%,cancerisaresearchfocusandadriverofexosomepublicationsgrowth.

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CancerTypesinExosomesandEVsCancerisanoldandgrowingthemeintheExosomesorECV’sarea.Breastcanceristhelargestoftheareasstudiedandhasagrowthrateof7.8%(4-yrCAGR).Skincancer(nextlargest)hasaCAGRof17%.

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CardiovascularThemesinExosomesThethemescardiovascularandcardiovasculardiseasearegrowthareasinexosomeresearchwith4-yrCAGRSof15%each.MyocardialInfarctionisakeywordwithat39%4-yrCAGR.Strokeisalsoagrowtharea.

Summary

•  TheProcess.Toidentifytrendsinexosomeresearch,weassembledacomprehensivedatabaseof47,643publicationsusingmultiple,overlappingsearchstrategies.Thisdatasetprovides–  acomprehensive,worldwideviewofexosomeresearch,and–  adatasetthatcanbeefficientlyminedtoprovideanunbiasedviewofresearchtrendsastheyactuallyexist.

•  Exosomesisarapidlyexpandingareawithagrowthratethatisalmostexponential.Theoverall4-yearCAGRforexosomesis9.3%,anindicatorofanareaexperiencingexplosivegrowth.WeusethisCAGRasabenchmark.Ifasub-trendhasaCAGRabove9.3%,wemarkthattrendasagrowthdriver.

•  Exosomeresearchisaworldwideenterprise.MostworkisconcentratedinEurope,theUS,andAsia(primarilyinChinaandJapan).

•  ThevocabularyinExosomesandExtracellularVesiclesiscomplex.Inourcomprehensivedatabase,weextracted1483variationsofan“-osome”name,10,461typesofparticles(twotothreewords)and30,665namesforvesicles(alsotwotothreewords).However,thewordsexosome,endosomeandextracellularvesiclearemostcommonnow.

•  UsingthedatabaseandPython’snaturallanguagetoolkit,wecanparseeachtitleandabstractintopartsofspeechremarkablyaccurately.Bylookingatthenounsandthe4-yearCAGRforeachnounwecanidentifythosewordsthathaveexceptionalgrowthrates.Applyingasizemetricaswellallowsustofindthoseareas(describedbythatnoun)thatmoststronglyinfluencegrowthinexosomeresearch.

•  Wetrack31,902pre-definedsegmentsinourresearch.Usingourpastexperience,wedefineasegmentaskeyword(s)describingbiomarkers,genes,materials,processes,technologies,andproductsorproductfeatures.Wefound6990ofourpre-definedsegmentsintheexosomedatabase.Analysisofthesetrendsalsoprovidesinsightsintogrowthareasinexosomes.

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