Table 1

Study design data extracted from articles included in systematic review

PublicationYearStroke modelSpeciesEV therapyIsolation methodRoute of administrationDoseTiming poststrokeLesion volume (Y/N)Functional outcomesStudy length
Chen et al272016Transient distal MCAO, filamentRatMini-pig AMSCs/AMSC-derived exosomesUltracentrifugationIntravenous100 µg3 hoursYCorner test60 days
Doeppner et al282015Transient MCAO, filamentMouseHuman BMSC-derived exosomesPEG precipitationIntravenousFrom 2×106 cells1, 3 and 5 daysYCorner test, rotarod, tightrope6 days
Geng et al292019Transient MCAO, filamentRatRat AMSC-derived miR-126±exosomesPrecipitationIntravenousNK2 hoursNFoot fault, mNSS14 days
Han et al302018ICH, autologous bloodRatRat BMSC-derived exosomesPrecipitationIntravenousDerived from 3×106 cells24 hoursYModified Morris water maze, mNSS, odour recognition28 days
Huang et al312018Transient MCAO, filamentRatPEDF-modified AMSC-derived exosomesPrecipitationIntraventricular100 µg/kg/day3 days prior to MCAOYN/A3 days
Jiang et al322018Permanent MCAO, filamentRatRat AMSC-derived miR-30d-5p±exosomesUltracentrifugationIntravenous80 µg0 hourYN/A3 days
Kalani et al182016Transient MCAO, filamentMouseMouse ESC-derived curcumin-loaded exosomesUltracentrifugationIntranasal10 µL total1 hour (+daily for 7 days)YBelayev neuroscore7 days
Lee et al332016Permanent MCAO, filamentRatHuman MSC-derived microvesicles, primed with normal/ischaemic brain extractUltracentrifugation (sucrose cushion), OptiPrepIntra-articular0.2 mg/kg48 hoursYBeam balance, modified torso twisting, mNSS, prehensile test7 days
Liu et al342019Transient MCAO, filamentRatRat BMSC (transferrin expressing)-derived enkephalin-loaded exosomesUltracentrifugationIntravenous500 µL × 1×105/mL2 hoursNForelimb flexion, inclined board test, 5-point neuroscore21 days
Moon et al352019Transient MCAO, filamentRatRat MSC or fibroblast-derived exosomesCentrifugation at 14 000 gIntravenous30 µg24 hoursNCylinder test, ladder walking, mNSS14 days
Otero-Ortega et al362017Transient subcortical, endothelin-1RatRat AMSC-derived exosomesPrecipitationIntravenous100 µg24 hoursYBeam walking,
modified Rogers test, rotarod
28 days
Otero-Ortega et al372018ICH, collagenaseRatRat AMSC-derived exosomesPrecipitationIntravenous100 µg24 hoursYBeam walking, modified Rogers test, rotarod28 days
Pan et al382016Transient MCAO, filamentMouseHuman brain microvascular cell-derived exosomesCentrifugation at 20 000 gIntravenous50 µg30 minY5-point neuroscore48 hours
Shan et al192013Transient MCAO, filamentRatMicroparticles from reperfusion-ischaemia injury or healthy ratsUltracentrifugationIntravenousNK30 min prereperfusionY18-point neuroscore9 days
Webb et al162018Transient MCAO, thromboembolicMouseHuman NSC and MSC-derived EVsUltrafiltrationIntravenousNK2, 14+38 hoursYAdhesive removal, beam walking, foot fault, hanging wire, neurological deficit score, novel object recognition, tail suspension48 hours
Webb et al172018Permanent MCAO, electrocoagulationPigHuman NSC EVsUltrafiltrationIntravenous2.7×1010 vesicles/kg2, 14+24 hoursYGait analysis, open field24 hours
Xin et al392013Transient MCAO, filamentRatRat BMSC-derived exosomesUltracentrifugation, sucrose step gradientIntravenous100 µg24 hoursYFoot fault, mNSS28 days
Xin et al402017aTransient MCAO, filamentRatRat BMSC-derived, wt/MiR-133b-/MiR-133b+exosomesUltracentrifugationIntra-articular3×1011 particles24 hoursNFoot fault, mNSS28 days
Xin et al412017Transient MCAO, filamentRatRat BMSC-derived MiR-17-92 cluster+exosomesUltracentrifugation, sucrose step gradientIntravenous100 µg24 hoursNFoot fault, mNSS28 days
Zheng et al152019Transient MCAO, filamentRatMouse macrophage-derived exosomes (LPS stimulated)UltracentrifugationIntravenous2 mg6 and 24 hoursYBelayev and Longa neuroscores24 hours
  • AMSC, adipose-derived mesenchymal stem cell; BMSC, bone marrow-derived mesenchymal stem cell;ESC, embryonic stem cell; EV, extracellular vesicle; ICH, intracerebral haemorrhage; LPS, lipopolysaccharide; MCAO, middle cerebral artery occlusion; mNSS, modified neurological severity score; MSC, mesenchymal stem cell;N/A, not applicable; NK, not known; NSC, neural stem cell;PEDF, pigment epithelial-derived factor; PEG, polyethylene Glycol; wt, wild type.