Systematic Reviews
Copyright ©The Author(s) 2020.
World J Stem Cells. May 26, 2020; 12(5): 381-405
Published online May 26, 2020. doi: 10.4252/wjsc.v12.i5.381
Table 1 Molecular imaging modalities
Image typeTechniquePhysical principleTracrerIn vitro imagingPreclincal imagingClinical ImagingSpatial ResolutionTemporal resolutionPenetration depthSensitivityStrengthsLimitations
Optical imagingBLIVisible lightLuminescent proteinsYesYesNo3-5 mmSeconds to minutes1-2 cmHigh (+++)High sensitivity, non-radioactive, cell expansionLow penetration depth, non-translational
FLIVisible or NIRF lightProteins or fluorescent dyesYesYesNo2-3 mmSeconds to minutes< 1 cmHigh (++)High sensitivity, non-radioactiveLow penetration depth, autofluorescence
Nuclear imagingPETHigh-energy γ-raysRadioisotopes [89 Zr (78.4 h), 18 F (1.83 h), 11 C (0.34 h), 64 Cu (12.7 h), 68 GA (1.13 h)]NoYesYes1-2 mmSeconds to minutesLimitlessHigh (++)High penetration depth, high sensitivityRadiation exposure, high cost
SPECTLow-energy γ-raysRadioisotopes [99 mTc (6.03 h), 123 I (13.2 h), 111 In (67.4 h)]NoYesYes1-2 mmMinutesLimitlessHigh (++)High penetration depth, high sensitivityRadiation exposure, high cost
Magnetic imagingMRIRadio wavesContrast agentsNoYesYes0.02-0.1 mmMinutes to hoursLimitlessLowHigh penetration depth, non-radioactive, high spatial resolutionHigh cost, low sensitivity and contrast
Table 2 Characteristics of the studies and the stem cells used
Ref.YrCountryCell typeSource of cellsMedium culture - %FBS
Lim et al[33]2019South KoreaMSCHuman (adipose tissue)DMEM - 10%FBS
Wang et al[29]2019ChinaMSCHuman (umbilical cord)EBM-2 - 0%FBS
Yun et al[30]2018South KoreaNSCHuman (telencephalon)NR
Argibay et al[38]2017SpainMSCRat (bone marrow)IMDM - 10%FBS
Duan et al[37]2017ChinaMSCRat (bone marrow)DMEM - 10%FBS
Lu et al[35]2017ChinaNPC-ImmMice (C17.2)DMEM - 10%FBS
Zhang et al[34]2017ChinaNSCRat (lateral ventricles)StemPro NSC - 0%FBS
Lin et al[36]2017ChinaMSCRat (bone marrow)DMEM -10%FBS
Zhang et al[39]2016ChinaNSCHuman (bone marrow)NR
Duan et al[40]2016ChinaMSCRat (bone marrow)DMEM - 10%FBS
Bai et al[42]2015ChinaMSCMice (bone marrow)EBM-2
Chen et al[28]2015ChinaMSCHuman (umbilical cord)DMEM-HG
Tan et al[41]2015JapanMSCRat(bone marrow)DMEM - 10%FBS,
Janowski et al[44]2014PolandNSCHuman (umbilical cord)DMEM-F12 - 2%FBS
Park et al[43]2014South KoreaMSCRatDMEM - 0%FBS
Zhang et al[45]2013ChinaNPC-ImmMice (neonatal cerebellum)DMEM - 10%FBS
Tarulli et al[46]2013CanadaMSCRat (bone marrow)αMEM - 20%FBS
Liu et al[47]2013ChinaNSCRat (neonate)DMEM-F12
Wang et al[48]2011ChinaMSCMice (bone marrow)DMEM
Lee et al[50]2009SingaporeMSCHuman (fetal bone marrow)DMEM - 10%FBS
Song et al[49]2009South KoreaNPC-ImmHuman (HB1.F3)DMEM - 5%FBS
Kim et al[51]2008South KoreaMSCHumanDMEM - 0%FBS
Guzman et al[52]2007United StatesNSCHumanHNCM
Syková et al[53]2006Czech RepublicMSC, rOECMice; Human; RatNR
Zhu et al[54]2005United StatesNSCHumanNR
Table 3 Characteristics of the contrast agents used in the stem cell labeling, homing and tracking analysis by molecular imaging modalities
Ref.Contrast agentConcentration (mg/mL)Core/Hydrodynamic size (nm)Coating agentZeta Potential (mV)Conjugated agent (Ex/Em: nm)Image detection modeR1/R2 (mmol-1. Sec-1)Developer
Lim et al[33]NP (BCN-Fe3O4)NR20/238.9BCN, chitosan+12.6Cy5.5 (675/695)Dual (Mgt, NIRF)NR/526.1Synthesized
Wang et al[29]Alkyl-SPIONRNR/80-120Alkyl-PEIApproximately +21.0NADual (Mgt, BLI)NR/549.7Synthesized
Yun et al[30]Zn0.4Fe2.6O4 (ZnMNP)12NRNRDextranNRNADual (Mgt, BLI)NRSynthesized
Argibay et al[38]Fe3O41NR3.7/94Dextran-11.0NAMono (Mgt)NR/701Synthesized
Duan et al[37]Fe3O4-LCP0.126/136PDLLA+18.0NAMono (Mgt)NR/500.2Synthesized
Lu et al[35]PAsp(DMA)-Lys-CA2 (C-NP)2NRNR/64.1NR+15.32Nile red (552/636)Dual (Mgt, VFL)NR/460.5Synthesized
PEG-Lys-CA2 (N-NP)2NR/69.4+0.10NR/462.9
Zhang et al[34]Ferritin2NANANANANADual (Mgt, NIRF)NRSynthesized
Lin et al[36]SPION0.25NR/128ASP+21.6NAMono (Mgt)NR/296Synthesized
Zhang et al[39]SPIONNR30/50DextranNRNAMono (Mgt)NR/300Synthesized
Duan et al[40]Fe3O4-LCP20.126/136PDLLA+18.0NAMono (Mgt)NR/500.2Synthesized
Fe3O421.006/10.8PLL+32.8NR/457.2
Bai et al[42]bCD-GdNRNA/24.4NANRCy5.5 (675/695) Rhod (565/620)Tri (Mgt, NIRF, VFL)8.6/NRSynthesized
Chen et al[28]GRMNB1NRNA/130SilicaNRNADual (Mgt, BLI)1.21/127.89Synthesized
Tan et al[41]γ-Fe2O3 (ferucarbotran)27.904/60CarboxydextranNRNAMono (Mgt)NRResovist®, Fujifilm RI Pharma Co. Ltd., Tokyo, Japan
Janowski et al[44]Fe3O42.008/35Dextran+31.0Rhod (565/620)Dual (Mgt, VFL)30.4/75.8BioPAL Inc, Worcester, MA, USA
Park et al[43]PCIONNR11/371.6PEG+28.6Rhod (565/620)Dual (Mgt, VFL)NRSynthesized
Zhang et al[45]fmSiO4@SPIONsNR30/151 30/148Silica-22.5FITC (490/525)Dual (Mgt, VFL)NR/309.53Synthesized
NR/231.74
fdSiO4@SPIONs-38.0
Tarulli et al[46]Fe3O4 (MPIO)NRNR/900DBP< 0DGF (480/520)Dual (Mgt, VFL)NRNR
Liu et al[47]SPIONNRNRNRNRNRMono (Mgt)NRNR
Wang et al[48]Fe3O4 (PMNC)NR8/120Silica-38.0Rhod (565/620)Dual (Mgt, VFL)3.81/435Synthesized
Lee et al[50]MGIONR5/602PMGNRNAMono (Mgt)NRSynthesized
Song et al[49]FeO1.44 (Feridex)11.205-6/50-180Dextran-12.0NAMono (Mgt)23.9/98.3Advanced Magnetic, Cambridge, MA, United States
Kim et al[51]FeO1.44 (Feridex)11.25-6/50-180Dextran-12NAMono (Mgt)23.9/98.3Advanced Magnetic, Cambridge, MA, United States
Guzman et al[52]FeO1.44 (Feridex)11.25-6/50-180Dextran-12NAMono (Mgt)23.9/98.3Berlex Laboratories, Wayne, NJ, United States
Syková et al[53]Fe3O4 (Endorem)15.84.3-5.6/150Dextran-12NAMono (Mgt)40/160Guerbet, Roissy, France
Zhu et al[54]FeO1.44 (Feridex)11.25-6/50-180Dextran-12NAMono (Mgt)23.9/98.3Advanced Magnetic, Cambridge, MA, United States
Table 4 Stem cell labeling process
Ref.CellsPassageContrast agentConcen-tration μg/mL)Incu-bation time (h)Strategy of interna-lizationEffici-encyQuantification
Cellular viability
Others analysis
(pgFe/cell)TechniqueMethodResults
Lim et al[33]MSCP5-P7NP(BCN-Fe3O4)3002Ac4ManNAz98.7%15.3ICP-MSCCK-8 assay> 95%CF, SEM, CEM, MRI
Wang et al[29]MSCP2-P7Alkyl-SPIOan appropriate amount of Alkyl-PEI/SPIO (N/P = 20)6PEIHigh Eff.NANACCK-8 assay> 90%BLI, MRI
Yun et al[30]NSCNRZnMNP50NRPLL: 1.5 g/mLNR4.6NRNANATEM, BLI
Argibay et al[38]MSCP0-P2, P9, P17Fe3O410024PLL: 1.5 μg/mLHigh Eff.0.9-7.7ICP-OESLDH assayNSDTEM
Duan et al[37]MSCP3-P5Fe3O4-LCP151.5PEIApproximately 100%Approximately 9AASCCK-8 assay> 90%TEM, MRI
Lu et al[35]NPCNRC-NP104PLL and LipofectaminApproximately 99.3%NANACCK-8 assay> 95%MRI, VFL
N-NPApproximately 8.7%
Zhang et al[34]NSCP2-P3FerritinMOI: 1024PLLApproximately 63%3.5AASCCK-8 assayNSDTEM, MRI, PB
Lin et al[36]MSCP5-P9ASP-SPION301NAApproximately 100%2.68AASCCK-8 assay> 90%MRI, TEM
Zhang et al[39]NSCNRAnti-CD15-SPIONNRNRNANRNANANANANA
Duan et al[40]MSCP3-P5Fe3O4-LCP151.5PEILCP > PLL8.373AASCCK-8 assay> 90%TEM, in vitro MRI
Fe3O42524PLL9.214
Bai et al[42]MSCNRbCD-Gd2 μmol24PLLNRNANANANANA
Chen et al[28]MSCNRGRMNB102NRHigh Eff.33.62AASMTT87.6BLI
Tan et al[41]MSCNRFerucarbotranNR24NAApproximately 95%NANANANANA
Janowski et al[44]NSCNRFe3O42548PLL: 375 ng/mLNRNANANININA
Park et al[43]MSCNRPCION10.25PLL, EMFNRNANANANATEM, MRI
Zhang et al[45]NPCNAfmNP5, 10, 20, 330.5, 1, 2, 3NAfmNP > fdNP5-30ICP-AESCCK-8 assay90%-98%TB
fdNP1-2.5NANANA
Tarulli et al[46]MSCNRMPIO18.824NA95%54Flow cytometryFlow cytometryApproximately 94%CF
Liu et al[47]NSCNRSPION1424NANRNRNRNININA
Wang et al[48]MSCNRPMNC0.5 mmol1NAApproximately 100%16-20ICP-OESCCK-8 assay> 95%TEM, CF, MRI
Lee et al[50]MSCP5, P6MGIO5024NAApproximately 97%33.3ICP-OESNI> 95%TEM, microarray
Song et al[49]NPCNRFeridex112.472NAApproximately 100%0.2AASTBUnaffectedMRI
Kim et al[51]MSCNRFeridex112-16PSNR2.6ICP/MSNININA
Guzman et al[52]NSCNRFeridex524PS: 2.5 μg/mL98%Halved every 3 d (%)Semiquantitative (MRI)Cell countingApproximately 92%NA
Syková et al[53]MSC, rOECNREndorem112.448-72NANRNANANANATEM
Zhu et al[54]NSCNRFeridexNR1EffecteneHigh Eff.NANANRNINA
Table 5 Stroke models induced by filament intraluminal middle cerebral artery, brain injury evaluation and animal features
Ref.Ischemia mechanismAnimals
n / NIschemia typeIschemia time (min)Filament typeAnesthesiaBrain induction area (AP; ML to bregma in mm)Blood flow analysisInjury evaluation
SpecieTypeSexWeight (g)Age (wk)
Yun et al[30]MCAoRatSDM240-260Adult13-8/50T303-0 nylon sutureNRMNINITTC, MRI
Argibay et al[38]MCAoRatWistarM280-300NR6/133T45silicon rubber-3%-4% sevofluraneMNILaser-DopplerMRI
Duan et al[37]MCAoRatSDM250-280Adult16/54NRNRNRNRMNINIMRI
Lu et al[35]MCAoRatSDNRNRNR6/12T904-0 nylon suture, silicone coated tip1% halothaneMNINIMRI
Zhang et al[34]MCAoRatSDNR250-280Adult1NR/30T120NRPB (40 mg/kg)MNINIMRI
Lin et al[36]MCAoRatSDM250-280Adult16/18T120NRNRMNINIMRI
Zhang et al[39]MCAoMiceC57BL/6JNR20-258NR/45T20Nylon poly-1-lysinecoatedPB (6 mL/kg)MNINIMRI
Duan et al[40]MCAoRatSDMNRAdult1NR/24NRNRNRNRMNINIMRI
Chen et al[28]MCAoMiceC57BL/6JM25-30Adult1NR/NRT120square knot using a 10 sutureCH (0.4 g/kg)zygoma/squamosal boneNIMRI
Tan et al[41]Lacunar infarctionRatWistarM240-260NRNR/22PNANA2%-4% ISO0; 3NIMRI
Zhang et al[45]MCAoMiceCD1FNR4NR/NRPNA6-0 rounded tip nylonNRMNINIMRI
Park et al[43]MCAoRatSDNR250-280NR8/16T120Micro clip 24 mmRompum (10 mg/kg) + Zoletil (30 mg/kg)MNINIMRI
Liu et al[47]MCAoRatSDM160-180NR6-8/48NRNRNylon10% CH (300 mg/kg)MNINIMRI
Wang et al[48]MCAoMiceCD1FNR47/21T1806-0 rounded tip nylonNRNINIMRI
Song et al[49]MCAoRatSDM250-300NR3/6T120NR4% ISOMNINIMRI
Kim et al[51]MCAoRatSDM250-300NR2-6/13PNANRket. (80-100 mg/kg) + AM (5 mg/kg)MNIEEGMRI
Guzman et al[52]MCAoRatSDMNRAdult15/10PNANAISOMNI + rhinal fissureNIMRI
GlobalMiceNOD-SCIDNRNR0-1PN12-16/28T5-10NACryoanestrhetizedNANIMRI
Table 6 Stroke models induced by the photothrombosis of middle cerebral artery, brain injury evaluation and animal features
Ref.Ischemia mechanismAnimals
n / NPhotosensitizer - rose bengal (dose; via)Laser application parameters
AnesthesiaBrain induction area(AP; ML to Bregma in mm)Injury evaluation
SpecieTypeSexWeight(g)Age (wk)Time (min)Diameter (mm)Wavelengh (nm)Power (W)
Lim et al[33]PTMiceBalb/c nudeM20-25103-5/1910 mg/mL; penile vein16NR561NRZoletil (50-30 mg/kg i.p.)0.5; 2.5MRI, NIRF, TTC
Wang et al[29]PTMiceBalb/c nudeF20-2384-6/39100 mg/kg154NRNRPB (50 mg/kg i.p)-2.0; 2.0MRI
Bai et al[42]PTMiceDb/DbMNR84/8100 mg/kg; i.p.15NRNRNR1% ISO0.0; 2.0MRI, NIRF
MiceWild typeMNR810/20100 mg/kg; i.p.15NRNRNR1% ISO0.0; 2.0MRI, NIRF
Tarulli et al[46]Focal devascularizationRatLong EvansMNR8-123/9NANANANANAISO + Ketoprofen3.0/-4.0; 1.5/4.5MRI
Lee et al[50]PTRatWistarFNRNRNR/227.5 mg/mL; tail vein10360360Ket. (7.5 mg/100 g) + Xyl. (1 mg/100 g)-2.0; -3.0MRI, TTC
Syková et al[53]PhotochemicalRatWistarMNR8-12NR/NRNRNANANANANRNIMRI
Table 7 Magnetic resonance imaging features for stem cell homing evaluation
Ref.Equipment systemAnalysis softwareMF (Tesla)SequenceWeighted images (TR/TE; ms)FOV; MT; ST (mm)Homing evaluation time
Lim et al[33]PC - Agilent TechnologiesImageJ (NIH)9.4T2T2: 4000/32.5NA; NA; 1.01, 3, 7, 10, 14 d
Wang et al[29]PC - PharmaScan - BrukerImageJ (NIH)7.0TSE FLASH GRET2: 3000/NA20 × 20; 256 × 256; 1.01, 3, 7 d
ParaVision (Bruker)T2*: 159.4/555 × 55; 256 × 256; 1.0
Yun et al[30]Philips Medical Systems; an animal coilNA3.0FSET2: 4000/8050; 256 × 256; 0.51 d, 3 w
Argibay et al[38]PC - Bio Spec - Bruker; surface coil arrayImageJ (NIH)9.4MGET2*: 2.9/1.519.2 × 19.2; 192 × 192; 1.04 h
Duan et al[37]Achieva - Philips Medical Systems; 4-channel rat coilImageJ (NIH)3.0FSET2: 800/6060; 256 × 256; 1.01-4, 6-8 wk
FFET2*: 500/18
Lu et al[35]Achieva - Philips Medical Systems; 4-channel rat coilNA3.0FSET2: 200/3160 × 60; 267 × 268; 1.01, 3, 7, 14 d
FFET2*: 500/18
Zhang et al[34]Achieva - Philips Medical SystemsImageJ (NIH)3.0FSET2: 800/6060 × 60; 256 × 256; 1.01-6 wk
PDWPDW: 3000/20
FFET2*: 500/18
Lin et al[36]Intera - Philips Medical SystemsImageJ (NIH)3.0Multi SET2: 2000/20-8080 × 80; 160 × 266; 2.01-6 wk
Zhang et al[39]PC - PharmaScan - BrukerImageJ (NIH)7.0Turbo RARET2: 6000/ 6030; 256 × 256; 0.52 d, 8 d
FLASH GRET2*: 400/3.5
Duan et al[40]Achieva - Philips Medical SystemsImageJ (NIH)3.0FSET2: 800/6060; 256 × 256; 1.01, 2, 3, 4, 6 wk
PDWPDW: 3000/20
FFET2*: 500/18
Bai et al[42]PC - PharmaScan - BrukerImageJ (NIH)7.0SET1: 500/1520 × 20; 256 × 256; 1.01, 3, 5, 7, 10, 14 d
FSET2: 2000/50
Chen et al[28]PC - Bio Spec - BrukerImageJ (NIH)7.0RARE SET2: 3000/5025.6; 256 × 256; 0.73 d, 7 d, 14 d
Tan et al[41]PC - Unity INOVA, VarianNR7.0SET2: 2500/6030 × 30; 512 × 512; NR1-42 d
Janowski et al[44]Sonata Maestro Class - Siemens; 8-channel head coilOsirix (Pixmeo) Amira (Visage Imaging)1.5SWIT2*: 49/40230; 168 × 256; 1.61 d, 1 wk, 1 mo, 2 mo, 4 mo
Park et al[43]Achieva - Philips Medical Systems; animal coilNA3.0SET2: 11000/125NA; 284 × 286; 0.70 h, 2 d
Zhang et al[45]Sigma - GE Healthcare; a human head coilNA3.0FSET2: 5840/10445 × 45; 256 × 256; 1.5-2.01 d, 3 d
Map MSME SET2: 3500/20-160
Tarulli et al[46]Sigma - GE HealthcareNA3.0FSET2: 4500/35-7540 × 40 × 17; 256 × 256; 1.01 d, 7 d, 14 d
3D-SPGRT2*: 25/740 × 40 × 20; 256 × 256; 1.0
Liu et al[47]Sigma - GE Healthcare; a rat coil3.0T2*T2*: 2560/6.86.0; NR; 1.61, 7, 21 d
Wang et al[48]Sigma - GE HealthcareNA3.0FSET2: 5840/10445 × 45; 256 × 256; 1.51, 7, 30 d
Lee et al[50]Sigma - GE Healthcare; a clinical coilNA1.5TSET2: 2000/8190; 192 × 192; 1.50, 1, 5, 12 d
GRE280/2020; 160 × 160; 1.5
Song et al[49]Sigma - GE HealthcareNA1.5T2T2: 3500/8060 × 60; 256 × 160; 2.01d, 3d, 1-4 wk
3D GRET2*: 50/2080 × 80; 256 × 160; 2.0
Kim et al[51]PC - Bio Spec - BrukerNA4.7SET1: 600/1440 × 30; 256 × 192; 1.02 d, 1 w, 2 w...10 wk
RARET2: 5000/90
FLASHT2*: 758 × 30
Guzman et al[52]PC - Varian Medical SystemsNA4.7SET2: 2500/4540; 256 × 256; 1.02 d, 7 d, 35 d
3D GRET2*: 600/530 × 30 × 30; 128× 128 × 128
Syková et al[53]PC - Bio Spec-BrukerNA4.7FGET2: NANA1 d, 1-7 wk
Zhu et al[54]Sigma - GE HealthcareNA3.0SET2: 200/20NA1 d, 7 d
Table 8 Near-infrared fluorescence imaging features for stem cell homing evaluation
Ref.AgentEquipmentSoftwareExcitation / Emission wavelength (nm)Time of expositionFollow-up
Lim et al[33]DBCO-Cy5.5IVIS Lumina Series III (PerkinElmer)Living Image (PerkinElmer)670/NA1 minIn vivo at 1, 3, 7, 10, 14 d; ex vivo at 2, 27, 30, 33, 36 h
Zhang et al[34]LV-FTH-EGFPsmall animal in vivo FLI system (in vivo FxPro; Carestream)MI (Carestream)487/509NA1, 2, 3, 4, 5, 6 wk
Bai et al[42]Cy5-5Maestro in vivo imaging system (CRi, Woburn)Maestro v. 2.10.0675/695NA1, 3, 5, 7, 10, 14 d
Table 9 Bioluminescence imaging features for stem cell homing evaluation
Ref.Lentiviral vectorEquipmentSoftwareSubstrateDoseImage acquisitionFollow-up
Wang et al[29]Luc2/eGFPIVIS Lumina Series III (Perkin-Elmer)NRD-luciferin (Promega, United States)100 mL (30 mg/mL)10 min after injection1 d, 3 d, 7 d
Yun et al[30]Fluc/eGFPIVIS® Spectrum imaging system (Perkin Elmer)NRD-luciferin (Promega, United States)150 mg/kgNR1 d, 1 wk, 3 wk
Chen et al[28]Luc/GFPIVIS Imaging System 200 Series (Caliper)Living Image 3.0 (Xenogen Corp.)D-luciferin (Caliper)270 mg/g15 min after injection0, 14 d
Table 10 Stem cell administration, homing and cellular therapeutic efficiency
Ref.Cell TypeImmuno-genicityTime from stroke (h)Cell administration
GroupsFollow-upOutcome
RouteNumberVolume (µL)BehaviorInfarct volumeMole-cular proteins/othersCells mi-gration
Lim et al[33]MSCXNGNRIC-CTL1 × 1065Stroke + cells vs Stroke-cells1, 3, 7, 10, 14 dNR(+)NR(+)
Wang et al[29]MSCXNG24ITC15 × 105100Alkyl-SPIO/siPHD2 > Alkyl-SPIO/si1, 3, 7 d(+) mNSS; FFT at 14 d(+) 7 d(+) Ki67; CD31 -7 d; (+) NeuN -14 d(+)
MSCXNG24ITC15 × 105100Alkyl-SPIO/si vs saline1, 3, 7 d(+) mNSS; FFT at 14 d(-) 7 d(+) Ki67; CD31 -7 d; (+) NeuN -14 d(+)
Yun et al[30]NSCXNG24IA-IC3 × 106100Mag-Cells > UL-Cells/sa-line0, 3, 5, 7, 21 d(+) Cilinder at 21dNR(+) MAP2; Nestin; GFAP; TuJ1 -7d(+)
Argibay et al[38]MSCALG8IA; IV-jugular2 × 105; 1 × 106300D-MNP-labeled MSC (IA × IV)4, 24, 72 h(-) Cilinder(-) at 14d(-) CD31; Ki67; DCX(+)
Duan et al[37]MSCALG48IC-CTL5 × 1053Labeled cell > UL-cells1, 2, 3, 4, 6, 8 wk(-) mNSS(-)(-) TUNNEL (-) GFP(+)
Labeled/UL vs control1, 2, 3, 4, 6, 8 wk(+) mNSS at 3, 4, 6, 8 wk(+) at 4, 6, 8 wk(+) TUNNEL 7-21 d, (+) GFP 7-21 d(+)
Lu et al[35]NPCALGNRIC-IPS5 × 1052.5labeling with N-NPS0, 3, 7, 14 dNR(+)(+) Nestin(+) low
labeling with C-NP0, 3, 7, 14 dNR(+)(+) Nestin(+)
Zhang et al[34]NSCXNG48IC-CTL5 × 1053FTH-EGFP-NSC > non trans-ducec NSC1, 2, 3, 4, 5, 6 wk(+) mNSS at 1-6 wk(+) at 1-6 wk(+) GFAP; Nestin; CD11b at 6 wk(+)
Lin et al[36]MSCALG48IC-CTL5 × 105NRASP-SPION vs UL vs PBS1, 2, 3, 4, 5, 6 wk(-) mNSS(-)(-) GFAP; NeuN; CD11(+)
Zhang et al[39]NSCXNG7dIC-CTLNR7Stroke pure > Stroke + Ara-C0, 2, 8 dNR(+) at 8 d(+) CD15+; Nestin at 8 d(+)
Duan et al[40]MSCALG48IC-CTL5 × 1053PLL-SPION or PM > UL1, 2, 3, 4, 5, 6 wkNR(+) at 4, 6 wk(-) GFP(+)
Bai et al[42]MSCXNG24IA - IC1 × 106100DM + RWJ + cell > DM + cells1, 3, 5, 7, 10, 14 dNR(+)(+) p38 MAPK at 7 d(+)2
Chen et al[28]MSCXNG30 minIV-femoral5 × 105Mag-cells > UL-cells0, 3, 7, 14 d(+) VM at 14, 28 d(+) at 14 d(+) TuJ1; NeuN; GFAP at 28 d; (+) RT-PCR1 at 28 d(+)
Tan et al[41]MSCALG7 dIC-CTL5 × 10510Stroke + cells over time0, 1, 7, 14, 21, 42 dNRNR(-) GFP and NeuN at 7 d; (+) GFP and NeuN at 6 wk(+)
Janowski et al[44]NSCAuTLNRIC2 × 10410Case over time0, 1, 7, 60, 120 d, 33 moNRNRNR(+)
Park et al[43]MSCXNG14dIC-CTL6 × 1055Pcion/pDNA MSC vs control1, 2 dNR(-)NR(+)
Zhang et al[45]NPCALG24IC-CTL5 × 1055fsiSPION-NPC vs control1, 3 dNR(+)(+) Nestin(+)2
NPCALG24IV-tail1 × 106300fsiSPION-NPC vs control1, 3 dNRNR(+) Nestin(+)
Tarulli et al[46]MSCXNG72IV-tail3 × 106700MPIO-BMSC vs UL-BMSC1, 7, 14 dNRNRNR(+)
Liu et al[47]NSCXNGNRIC-CTL3 × 1045Stroke + NSC_FA > Stroke + NSC1, 7 dNRNR(+) Sox-2 BrdU at 21 d(+)
Wang et al[48]MSCXNG7dIC-CTL1 × 1055FMNC-MSC > UL-MSC vs control (FMNC)0, 1, 7, 30 dNRNR(+) TuJ1(+)
Lee et al[50]MSCXNG48IC-CTL2 × 1045M600-MSC vs FC-MSC1, 5, 12 dNRNRNR(+)
MSCXNG48IV-tail2 × 106500M600-MSC vs control5, 12 dNRNRNR(+)
Song et al[49]NPCXNG24IC-IPS4 × 1055FO-NPC vs control1, 3, 7, 14, 21, 28 dNRNR(+) BrdU; GFAP at 28 d(+)
NPCXNG24IV-tail4 × 106500FO-NPC vs control1, 3, 7, 14, 21, 28 dNRNR(+) BrdU; GFAP at 28 d(+)
Kim et al[51]MSCAuTL7dIC-IPS/CTL1 × 1052Feridex®-labeled hMSC over time for both vias2d, 1, 2, 4, 6, 8, 10 wkNRNR(-) GFAP; TH; MAP2; TuJ1; Nestin at 10 wk(+)
Guzman et al[52]NSCXNG7dIC-CTL3 × 105/5 × 104NSC-SCns-SPION3, 9, 12,18 wkNRNR(+) SC121 or SC101; TuJ1; GFAP; MAP2 at 18 wk(+)
Syková et al[53]rOECALGNRIC-CTLNRNROEC-SPION over time3-7 wkNRNR(+) NeuN; GFAP at 28 d(+)
MSCXNGNRIV-femoralNRNRMSC over time6-30 dNRNR(+) NeuN; GFAP at 28 d(+)
Zhu et al[54]NSCAuTLNRICNRNRPatients treat with NSC and no treat2 yr(+) SEP and DRS at 6, 9 mo(+) cells uptake by PET at 3, 6 moNI(+)