Systematic Reviews
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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
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 type Technique Physical principle Tracrer In vitro imagingPreclincal imaging Clinical Imaging Spatial Resolution Temporal resolution Penetration depth Sensitivity Strengths Limitations Optical imaging BLI Visible light Luminescent proteins Yes Yes No 3-5 mm Seconds to minutes 1-2 cm High (+++) High sensitivity, non-radioactive, cell expansion Low penetration depth, non-translational FLI Visible or NIRF light Proteins or fluorescent dyes Yes Yes No 2-3 mm Seconds to minutes < 1 cm High (++) High sensitivity, non-radioactive Low penetration depth, autofluorescence Nuclear imaging PET High-energy γ-rays Radioisotopes [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)] No Yes Yes 1-2 mm Seconds to minutes Limitless High (++) High penetration depth, high sensitivity Radiation exposure, high cost SPECT Low-energy γ-rays Radioisotopes [99 mTc (6.03 h), 123 I (13.2 h), 111 In (67.4 h)] No Yes Yes 1-2 mm Minutes Limitless High (++) High penetration depth, high sensitivity Radiation exposure, high cost Magnetic imaging MRI Radio waves Contrast agents No Yes Yes 0.02-0.1 mm Minutes to hours Limitless Low High penetration depth, non-radioactive, high spatial resolution High cost, low sensitivity and contrast
Table 2 Characteristics of the studies and the stem cells used
Ref .Yr Country Cell type Source of cells Medium culture - %FBS Lim et al [33 ] 2019 South Korea MSC Human (adipose tissue) DMEM - 10%FBS Wang et al [29 ] 2019 China MSC Human (umbilical cord) EBM-2 - 0%FBS Yun et al [30 ] 2018 South Korea NSC Human (telencephalon) NR Argibay et al [38 ] 2017 Spain MSC Rat (bone marrow) IMDM - 10%FBS Duan et al [37 ] 2017 China MSC Rat (bone marrow) DMEM - 10%FBS Lu et al [35 ] 2017 China NPC-Imm Mice (C17.2) DMEM - 10%FBS Zhang et al [34 ] 2017 China NSC Rat (lateral ventricles) StemPro NSC - 0%FBS Lin et al [36 ] 2017 China MSC Rat (bone marrow) DMEM -10%FBS Zhang et al [39 ] 2016 China NSC Human (bone marrow) NR Duan et al [40 ] 2016 China MSC Rat (bone marrow) DMEM - 10%FBS Bai et al [42 ] 2015 China MSC Mice (bone marrow) EBM-2 Chen et al [28 ] 2015 China MSC Human (umbilical cord) DMEM-HG Tan et al [41 ] 2015 Japan MSC Rat(bone marrow) DMEM - 10%FBS, Janowski et al [44 ] 2014 Poland NSC Human (umbilical cord) DMEM-F12 - 2%FBS Park et al [43 ] 2014 South Korea MSC Rat DMEM - 0%FBS Zhang et al [45 ] 2013 China NPC-Imm Mice (neonatal cerebellum) DMEM - 10%FBS Tarulli et al [46 ] 2013 Canada MSC Rat (bone marrow) αMEM - 20%FBS Liu et al [47 ] 2013 China NSC Rat (neonate) DMEM-F12 Wang et al [48 ] 2011 China MSC Mice (bone marrow) DMEM Lee et al [50 ] 2009 Singapore MSC Human (fetal bone marrow) DMEM - 10%FBS Song et al [49 ] 2009 South Korea NPC-Imm Human (HB1.F3) DMEM - 5%FBS Kim et al [51 ] 2008 South Korea MSC Human DMEM - 0%FBS Guzman et al [52 ] 2007 United States NSC Human HNCM Syková et al [53 ] 2006 Czech Republic MSC, rOEC Mice; Human; Rat NR Zhu et al [54 ] 2005 United States NSC Human NR
Table 3 Characteristics of the contrast agents used in the stem cell labeling, homing and tracking analysis by molecular imaging modalities
Ref .Contrast agent Concentration (mg/mL) Core/Hydrodynamic size (nm) Coating agent Zeta Potential (mV) Conjugated agent (Ex/Em: nm) Image detection mode R1/R2 (mmol-1 . Sec-1 ) Developer Lim et al [33 ] NP (BCN-Fe3 O4 ) NR 20/238.9 BCN, chitosan +12.6 Cy5.5 (675/695) Dual (Mgt, NIRF) NR/526.1 Synthesized Wang et al [29 ] Alkyl-SPIO NR NR/80-120 Alkyl-PEI Approximately +21.0 NA Dual (Mgt, BLI) NR/549.7 Synthesized Yun et al [30 ] Zn0.4 Fe2.6 O4 (ZnMNP)1 2 NR NR Dextran NR NA Dual (Mgt, BLI) NR Synthesized Argibay et al [38 ] Fe3 O4 1 NR 3.7/94 Dextran -11.0 NA Mono (Mgt) NR/701 Synthesized Duan et al [37 ] Fe3 O4 -LCP 0.12 6/136 PDLLA +18.0 NA Mono (Mgt) NR/500.2 Synthesized Lu et al [35 ] PAsp(DMA)-Lys-CA2 (C-NP)2 NR NR/64.1 NR +15.32 Nile red (552/636) Dual (Mgt, VFL) NR/460.5 Synthesized PEG-Lys-CA2 (N-NP)2 NR/69.4 +0.10 NR/462.9 Zhang et al [34 ] Ferritin2 NA NA NA NA NA Dual (Mgt, NIRF) NR Synthesized Lin et al [36 ] SPION 0.25 NR/128 ASP +21.6 NA Mono (Mgt) NR/296 Synthesized Zhang et al [39 ] SPION NR 30/50 Dextran NR NA Mono (Mgt) NR/300 Synthesized Duan et al [40 ] Fe3 O4 -LCP2 0.12 6/136 PDLLA +18.0 NA Mono (Mgt) NR/500.2 Synthesized Fe3 O4 2 1.00 6/10.8 PLL +32.8 NR/457.2 Bai et al [42 ] bCD-Gd NR NA/24.4 NA NR Cy5.5 (675/695) Rhod (565/620) Tri (Mgt, NIRF, VFL) 8.6/NR Synthesized Chen et al [28 ] GRMNB1 NR NA/130 Silica NR NA Dual (Mgt, BLI) 1.21/127.89 Synthesized Tan et al [41 ] γ-Fe2 O3 (ferucarbotran) 27.90 4/60 Carboxydextran NR NA Mono (Mgt) NR Resovist® , Fujifilm RI Pharma Co. Ltd., Tokyo, Japan Janowski et al [44 ] Fe3 O4 2.00 8/35 Dextran +31.0 Rhod (565/620) Dual (Mgt, VFL) 30.4/75.8 BioPAL Inc, Worcester, MA, USA Park et al [43 ] PCION NR 11/371.6 PEG +28.6 Rhod (565/620) Dual (Mgt, VFL) NR Synthesized Zhang et al [45 ] fmSiO4 @SPIONs NR 30/151 30/148 Silica -22.5 FITC (490/525) Dual (Mgt, VFL) NR/309.53 Synthesized NR/231.74 fdSiO4 @SPIONs -38.0 Tarulli et al [46 ] Fe3 O4 (MPIO) NR NR/900 DBP < 0 DGF (480/520) Dual (Mgt, VFL) NR NR Liu et al [47 ] SPION NR NR NR NR NR Mono (Mgt) NR NR Wang et al [48 ] Fe3 O4 (PMNC) NR 8/120 Silica -38.0 Rhod (565/620) Dual (Mgt, VFL) 3.81/435 Synthesized Lee et al [50 ] MGIO NR 5/602 PMG NR NA Mono (Mgt) NR Synthesized Song et al [49 ] FeO1.44 (Feridex) 11.20 5-6/50-180 Dextran -12.0 NA Mono (Mgt) 23.9/98.3 Advanced Magnetic, Cambridge, MA, United States Kim et al [51 ] FeO1.44 (Feridex) 11.2 5-6/50-180 Dextran -12 NA Mono (Mgt) 23.9/98.3 Advanced Magnetic, Cambridge, MA, United States Guzman et al [52 ] FeO1.44 (Feridex) 11.2 5-6/50-180 Dextran -12 NA Mono (Mgt) 23.9/98.3 Berlex Laboratories, Wayne, NJ, United States Syková et al [53 ] Fe3 O4 (Endorem) 15.8 4.3-5.6/150 Dextran -12 NA Mono (Mgt) 40/160 Guerbet, Roissy, France Zhu et al [54 ] FeO1.44 (Feridex) 11.2 5-6/50-180 Dextran -12 NA Mono (Mgt) 23.9/98.3 Advanced Magnetic, Cambridge, MA, United States
Table 4 Stem cell labeling process
Ref .Cells Passage Contrast agent Concen-tration μg/mL) Incu-bation time (h) Strategy of interna-lization Effici-ency Quantification Cellular viability Others analysis (pgFe/cell) Technique Method Results Lim et al [33 ] MSC P5-P7 NP(BCN-Fe3 O4 ) 300 2 Ac4ManNAz 98.7% 15.3 ICP-MS CCK-8 assay > 95% CF, SEM, CEM, MRI Wang et al [29 ] MSC P2-P7 Alkyl-SPIO an appropriate amount of Alkyl-PEI/SPIO (N/P = 20) 6 PEI High Eff. NA NA CCK-8 assay > 90% BLI, MRI Yun et al [30 ] NSC NR ZnMNP 50 NR PLL: 1.5 g/mL NR 4.6 NR NA NA TEM, BLI Argibay et al [38 ] MSC P0-P2, P9, P17 Fe3 O4 100 24 PLL: 1.5 μg/mL High Eff. 0.9-7.7 ICP-OES LDH assay NSD TEM Duan et al [37 ] MSC P3-P5 Fe3 O4 -LCP 15 1.5 PEI Approximately 100% Approximately 9 AAS CCK-8 assay > 90% TEM, MRI Lu et al [35 ] NPC NR C-NP 10 4 PLL and Lipofectamin Approximately 99.3% NA NA CCK-8 assay > 95% MRI, VFL N-NP Approximately 8.7% Zhang et al [34 ] NSC P2-P3 Ferritin MOI: 10 24 PLL Approximately 63% 3.5 AAS CCK-8 assay NSD TEM, MRI, PB Lin et al [36 ] MSC P5-P9 ASP-SPION 30 1 NA Approximately 100% 2.68 AAS CCK-8 assay > 90% MRI, TEM Zhang et al [39 ] NSC NR Anti-CD15-SPION NR NR NA NR NA NA NA NA NA Duan et al [40 ] MSC P3-P5 Fe3 O4 -LCP 15 1.5 PEI LCP > PLL 8.373 AAS CCK-8 assay > 90% TEM, in vitro MRI Fe3 O4 25 24 PLL 9.214 Bai et al [42 ] MSC NR bCD-Gd 2 μmol 24 PLL NR NA NA NA NA NA Chen et al [28 ] MSC NR GRMNB 10 2 NR High Eff. 33.62 AAS MTT 87.6 BLI Tan et al [41 ] MSC NR Ferucarbotran NR 24 NA Approximately 95% NA NA NA NA NA Janowski et al [44 ] NSC NR Fe3 O4 25 48 PLL: 375 ng/mL NR NA NA NI NI NA Park et al [43 ] MSC NR PCION 1 0.25 PLL, EMF NR NA NA NA NA TEM, MRI Zhang et al [45 ] NPC NA fmNP 5, 10, 20, 33 0.5, 1, 2, 3 NA fmNP > fdNP 5-30 ICP-AES CCK-8 assay 90%-98% TB fdNP 1-2.5 NA NA NA Tarulli et al [46 ] MSC NR MPIO 18.8 24 NA 95% 54 Flow cytometry Flow cytometry Approximately 94% CF Liu et al [47 ] NSC NR SPION 14 24 NA NR NR NR NI NI NA Wang et al [48 ] MSC NR PMNC 0.5 mmol 1 NA Approximately 100% 16-20 ICP-OES CCK-8 assay > 95% TEM, CF, MRI Lee et al [50 ] MSC P5, P6 MGIO 50 24 NA Approximately 97% 33.3 ICP-OES NI > 95% TEM, microarray Song et al [49 ] NPC NR Feridex 112.4 72 NA Approximately 100% 0.2 AAS TB Unaffected MRI Kim et al [51 ] MSC NR Feridex 1 12-16 PS NR 2.6 ICP/MS NI NI NA Guzman et al [52 ] NSC NR Feridex 5 24 PS: 2.5 μg/mL 98% Halved every 3 d (%) Semiquantitative (MRI) Cell counting Approximately 92% NA Syková et al [53 ] MSC, rOEC NR Endorem 112.4 48-72 NA NR NA NA NA NA TEM Zhu et al [54 ] NSC NR Feridex NR 1 Effectene High Eff. NA NA NR NI NA
Table 5 Stroke models induced by filament intraluminal middle cerebral artery, brain injury evaluation and animal features
Ref .Ischemia mechanism Animals n / N Ischemia type Ischemia time (min) Filament type Anesthesia Brain induction area (AP; ML to bregma in mm) Blood flow analysis Injury evaluation Specie Type Sex Weight (g) Age (wk) Yun et al [30 ] MCAo Rat SD M 240-260 Adult1 3-8/50 T 30 3-0 nylon suture NR MNI NI TTC, MRI Argibay et al [38 ] MCAo Rat Wistar M 280-300 NR 6/133 T 45 silicon rubber- 3%-4% sevoflurane MNI Laser-Doppler MRI Duan et al [37 ] MCAo Rat SD M 250-280 Adult1 6/54 NR NR NR NR MNI NI MRI Lu et al [35 ] MCAo Rat SD NR NR NR 6/12 T 90 4-0 nylon suture, silicone coated tip 1% halothane MNI NI MRI Zhang et al [34 ] MCAo Rat SD NR 250-280 Adult1 NR/30 T 120 NR PB (40 mg/kg) MNI NI MRI Lin et al [36 ] MCAo Rat SD M 250-280 Adult1 6/18 T 120 NR NR MNI NI MRI Zhang et al [39 ] MCAo Mice C57BL/6J NR 20-25 8 NR/45 T 20 Nylon poly-1-lysinecoated PB (6 mL/kg) MNI NI MRI Duan et al [40 ] MCAo Rat SD M NR Adult1 NR/24 NR NR NR NR MNI NI MRI Chen et al [28 ] MCAo Mice C57BL/6J M 25-30 Adult1 NR/NR T 120 square knot using a 10 suture CH (0.4 g/kg) zygoma/squamosal bone NI MRI Tan et al [41 ] Lacunar infarction Rat Wistar M 240-260 NR NR/22 P NA NA 2%-4% ISO 0; 3 NI MRI Zhang et al [45 ] MCAo Mice CD1 F NR 4 NR/NR P NA 6-0 rounded tip nylon NR MNI NI MRI Park et al [43 ] MCAo Rat SD NR 250-280 NR 8/16 T 120 Micro clip 24 mm Rompum (10 mg/kg) + Zoletil (30 mg/kg) MNI NI MRI Liu et al [47 ] MCAo Rat SD M 160-180 NR 6-8/48 NR NR Nylon 10% CH (300 mg/kg) MNI NI MRI Wang et al [48 ] MCAo Mice CD1 F NR 4 7/21 T 180 6-0 rounded tip nylon NR NI NI MRI Song et al [49 ] MCAo Rat SD M 250-300 NR 3/6 T 120 NR 4% ISO MNI NI MRI Kim et al [51 ] MCAo Rat SD M 250-300 NR 2-6/13 P NA NR ket. (80-100 mg/kg) + AM (5 mg/kg) MNI EEG MRI Guzman et al [52 ] MCAo Rat SD M NR Adult1 5/10 P NA NA ISO MNI + rhinal fissure NI MRI Global Mice NOD-SCID NR NR 0-1PN 12-16/28 T 5-10 NA Cryoanestrhetized NA NI MRI
Table 6 Stroke models induced by the photothrombosis of middle cerebral artery, brain injury evaluation and animal features
Ref .Ischemia mechanism Animals n / N Photosensitizer - rose bengal (dose; via ) Laser application parameters Anesthesia Brain induction area (AP; ML to Bregma in mm) Injury evaluation Specie Type Sex Weight (g) Age (wk) Time (min) Diameter (mm) Wavelengh (nm) Power (W) Lim et al [33 ] PT Mice Balb/c nude M 20-25 10 3-5/19 10 mg/mL; penile vein 16 NR 561 NR Zoletil (50-30 mg/kg i.p.) 0.5; 2.5 MRI, NIRF, TTC Wang et al [29 ] PT Mice Balb/c nude F 20-23 8 4-6/39 100 mg/kg 15 4 NR NR PB (50 mg/kg i.p) -2.0; 2.0 MRI Bai et al [42 ] PT Mice Db/Db M NR 8 4/8 100 mg/kg; i.p. 15 NR NR NR 1% ISO 0.0; 2.0 MRI, NIRF Mice Wild type M NR 8 10/20 100 mg/kg; i.p. 15 NR NR NR 1% ISO 0.0; 2.0 MRI, NIRF Tarulli et al [46 ] Focal devascularization Rat Long Evans M NR 8-12 3/9 NA NA NA NA NA ISO + Ketoprofen 3.0/-4.0; 1.5/4.5 MRI Lee et al [50 ] PT Rat Wistar F NR NR NR/22 7.5 mg/mL; tail vein 10 3 603 60 Ket. (7.5 mg/100 g) + Xyl. (1 mg/100 g) -2.0; -3.0 MRI, TTC Syková et al [53 ] Photochemical Rat Wistar M NR 8-12 NR/NR NR NA NA NA NA NR NI MRI
Table 7 Magnetic resonance imaging features for stem cell homing evaluation
Ref .Equipment system Analysis software MF (Tesla) Sequence Weighted images (TR/TE; ms) FOV; MT; ST (mm) Homing evaluation time Lim et al [33 ] PC - Agilent Technologies ImageJ (NIH) 9.4 T2 T2: 4000/32.5 NA; NA; 1.0 1, 3, 7, 10, 14 d Wang et al [29 ] PC - PharmaScan - Bruker ImageJ (NIH) 7.0 TSE FLASH GRE T2: 3000/NA 20 × 20; 256 × 256; 1.0 1, 3, 7 d ParaVision (Bruker) T2*: 159.4/5 55 × 55; 256 × 256; 1.0 Yun et al [30 ] Philips Medical Systems; an animal coil NA 3.0 FSE T2: 4000/80 50; 256 × 256; 0.5 1 d, 3 w Argibay et al [38 ] PC - Bio Spec - Bruker; surface coil array ImageJ (NIH) 9.4 MGE T2*: 2.9/1.5 19.2 × 19.2; 192 × 192; 1.0 4 h Duan et al [37 ] Achieva - Philips Medical Systems; 4-channel rat coil ImageJ (NIH) 3.0 FSE T2: 800/60 60; 256 × 256; 1.0 1-4, 6-8 wk FFE T2*: 500/18 Lu et al [35 ] Achieva - Philips Medical Systems; 4-channel rat coil NA 3.0 FSE T2: 200/31 60 × 60; 267 × 268; 1.0 1, 3, 7, 14 d FFE T2*: 500/18 Zhang et al [34 ] Achieva - Philips Medical Systems ImageJ (NIH) 3.0 FSE T2: 800/60 60 × 60; 256 × 256; 1.0 1-6 wk PDW PDW: 3000/20 FFE T2*: 500/18 Lin et al [36 ] Intera - Philips Medical Systems ImageJ (NIH) 3.0 Multi SE T2: 2000/20-80 80 × 80; 160 × 266; 2.0 1-6 wk Zhang et al [39 ] PC - PharmaScan - Bruker ImageJ (NIH) 7.0 Turbo RARE T2: 6000/ 60 30; 256 × 256; 0.5 2 d, 8 d FLASH GRE T2*: 400/3.5 Duan et al [40 ] Achieva - Philips Medical Systems ImageJ (NIH) 3.0 FSE T2: 800/60 60; 256 × 256; 1.0 1, 2, 3, 4, 6 wk PDW PDW: 3000/20 FFE T2*: 500/18 Bai et al [42 ] PC - PharmaScan - Bruker ImageJ (NIH) 7.0 SE T1: 500/15 20 × 20; 256 × 256; 1.0 1, 3, 5, 7, 10, 14 d FSE T2: 2000/50 Chen et al [28 ] PC - Bio Spec - Bruker ImageJ (NIH) 7.0 RARE SE T2: 3000/50 25.6; 256 × 256; 0.7 3 d, 7 d, 14 d Tan et al [41 ] PC - Unity INOVA, Varian NR 7.0 SE T2: 2500/60 30 × 30; 512 × 512; NR 1-42 d Janowski et al [44 ] Sonata Maestro Class - Siemens; 8-channel head coil Osirix (Pixmeo) Amira (Visage Imaging) 1.5 SWI T2*: 49/40 230; 168 × 256; 1.6 1 d, 1 wk, 1 mo, 2 mo, 4 mo Park et al [43 ] Achieva - Philips Medical Systems; animal coil NA 3.0 SE T2: 11000/125 NA; 284 × 286; 0.7 0 h, 2 d Zhang et al [45 ] Sigma - GE Healthcare; a human head coil NA 3.0 FSE T2: 5840/104 45 × 45; 256 × 256; 1.5-2.0 1 d, 3 d Map MSME SE T2: 3500/20-160 Tarulli et al [46 ] Sigma - GE Healthcare NA 3.0 FSE T2: 4500/35-75 40 × 40 × 17; 256 × 256; 1.0 1 d, 7 d, 14 d 3D-SPGR T2*: 25/7 40 × 40 × 20; 256 × 256; 1.0 Liu et al [47 ] Sigma - GE Healthcare; a rat coil 3.0 T2* T2*: 2560/6.8 6.0; NR; 1.6 1, 7, 21 d Wang et al [48 ] Sigma - GE Healthcare NA 3.0 FSE T2: 5840/104 45 × 45; 256 × 256; 1.5 1, 7, 30 d Lee et al [50 ] Sigma - GE Healthcare; a clinical coil NA 1.5 TSE T2: 2000/81 90; 192 × 192; 1.5 0, 1, 5, 12 d GRE 280/20 20; 160 × 160; 1.5 Song et al [49 ] Sigma - GE Healthcare NA 1.5 T2 T2: 3500/80 60 × 60; 256 × 160; 2.0 1d, 3d, 1-4 wk 3D GRE T2*: 50/20 80 × 80; 256 × 160; 2.0 Kim et al [51 ] PC - Bio Spec - Bruker NA 4.7 SE T1: 600/14 40 × 30; 256 × 192; 1.0 2 d, 1 w, 2 w...10 wk RARE T2: 5000/90 FLASH T2*: 758 × 30 Guzman et al [52 ] PC - Varian Medical Systems NA 4.7 SE T2: 2500/45 40; 256 × 256; 1.0 2 d, 7 d, 35 d 3D GRE T2*: 600/5 30 × 30 × 30; 128× 128 × 128 Syková et al [53 ] PC - Bio Spec-Bruker NA 4.7 FGE T2: NA NA 1 d, 1-7 wk Zhu et al [54 ] Sigma - GE Healthcare NA 3.0 SE T2: 200/20 NA 1 d, 7 d
Table 8 Near-infrared fluorescence imaging features for stem cell homing evaluation
Ref .Agent Equipment Software Excitation / Emission wavelength (nm) Time of exposition Follow-up Lim et al [33 ] DBCO-Cy5.5 IVIS Lumina Series III (PerkinElmer) Living Image (PerkinElmer) 670/NA 1 min In vivo at 1, 3, 7, 10, 14 d; ex vivo at 2, 27, 30, 33, 36 hZhang et al [34 ] LV-FTH-EGFP small animal in vivo FLI system (in vivo FxPro; Carestream) MI (Carestream) 487/509 NA 1, 2, 3, 4, 5, 6 wk Bai et al [42 ] Cy5-5 Maestro in vivo imaging system (CRi, Woburn) Maestro v. 2.10.0 675/695 NA 1, 3, 5, 7, 10, 14 d
Table 9 Bioluminescence imaging features for stem cell homing evaluation
Ref .Lentiviral vector Equipment Software Substrate Dose Image acquisition Follow-up Wang et al [29 ] Luc2/eGFP IVIS Lumina Series III (Perkin-Elmer) NR D-luciferin (Promega, United States) 100 mL (30 mg/mL) 10 min after injection 1 d, 3 d, 7 d Yun et al [30 ] Fluc/eGFP IVIS® Spectrum imaging system (Perkin Elmer) NR D-luciferin (Promega, United States) 150 mg/kg NR 1 d, 1 wk, 3 wk Chen et al [28 ] Luc/GFP IVIS Imaging System 200 Series (Caliper) Living Image 3.0 (Xenogen Corp.) D-luciferin (Caliper) 270 mg/g 15 min after injection 0, 14 d
Table 10 Stem cell administration, homing and cellular therapeutic efficiency
Ref .Cell Type Immuno-genicity Time from stroke (h) Cell administration Groups Follow-up Outcome Route Number Volume (µL) Behavior Infarct volume Mole-cular proteins/others Cells mi-gration Lim et al [33 ] MSC XNG NR IC-CTL 1 × 106 5 Stroke + cells vs Stroke-cells 1, 3, 7, 10, 14 d NR (+) NR (+) Wang et al [29 ] MSC XNG 24 ITC1 5 × 105 100 Alkyl-SPIO/siPHD2 > Alkyl-SPIO/si 1, 3, 7 d (+) mNSS; FFT at 14 d (+) 7 d (+) Ki67; CD31 -7 d; (+) NeuN -14 d (+) MSC XNG 24 ITC1 5 × 105 100 Alkyl-SPIO/si vs saline 1, 3, 7 d (+) mNSS; FFT at 14 d (-) 7 d (+) Ki67; CD31 -7 d; (+) NeuN -14 d (+) Yun et al [30 ] NSC XNG 24 IA-IC 3 × 106 100 Mag-Cells > UL-Cells/sa-line 0, 3, 5, 7, 21 d (+) Cilinder at 21d NR (+) MAP2; Nestin; GFAP; TuJ1 -7d (+) Argibay et al [38 ] MSC ALG 8 IA; IV-jugular 2 × 105 ; 1 × 106 300 D-MNP-labeled MSC (IA × IV) 4, 24, 72 h (-) Cilinder (-) at 14d (-) CD31; Ki67; DCX (+) Duan et al [37 ] MSC ALG 48 IC-CTL 5 × 105 3 Labeled cell > UL-cells 1, 2, 3, 4, 6, 8 wk (-) mNSS (-) (-) TUNNEL (-) GFP (+) Labeled/UL vs control 1, 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 ] NPC ALG NR IC-IPS 5 × 105 2.5 labeling with N-NPS 0, 3, 7, 14 d NR (+) (+) Nestin (+) low labeling with C-NP 0, 3, 7, 14 d NR (+) (+) Nestin (+) Zhang et al [34 ] NSC XNG 48 IC-CTL 5 × 105 3 FTH-EGFP-NSC > non trans-ducec NSC 1, 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 ] MSC ALG 48 IC-CTL 5 × 105 NR ASP-SPION vs UL vs PBS 1, 2, 3, 4, 5, 6 wk (-) mNSS (-) (-) GFAP; NeuN; CD11 (+) Zhang et al [39 ] NSC XNG 7d IC-CTL NR 7 Stroke pure > Stroke + Ara-C 0, 2, 8 d NR (+) at 8 d (+) CD15+; Nestin at 8 d (+) Duan et al [40 ] MSC ALG 48 IC-CTL 5 × 105 3 PLL-SPION or PM > UL 1, 2, 3, 4, 5, 6 wk NR (+) at 4, 6 wk (-) GFP (+) Bai et al [42 ] MSC XNG 24 IA - IC 1 × 106 100 DM + RWJ + cell > DM + cells 1, 3, 5, 7, 10, 14 d NR (+) (+) p38 MAPK at 7 d (+)2 Chen et al [28 ] MSC XNG 30 min IV-femoral 5 × 105 Mag-cells > UL-cells 0, 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 ] MSC ALG 7 d IC-CTL 5 × 105 10 Stroke + cells over time 0, 1, 7, 14, 21, 42 d NR NR (-) GFP and NeuN at 7 d; (+) GFP and NeuN at 6 wk (+) Janowski et al [44 ] NSC AuTL NR IC 2 × 104 10 Case over time 0, 1, 7, 60, 120 d, 33 mo NR NR NR (+) Park et al [43 ] MSC XNG 14d IC-CTL 6 × 105 5 Pcion/pDNA MSC vs control 1, 2 d NR (-) NR (+) Zhang et al [45 ] NPC ALG 24 IC-CTL 5 × 105 5 fsiSPION-NPC vs control 1, 3 d NR (+) (+) Nestin (+)2 NPC ALG 24 IV-tail 1 × 106 300 fsiSPION-NPC vs control 1, 3 d NR NR (+) Nestin (+) Tarulli et al [46 ] MSC XNG 72 IV-tail 3 × 106 700 MPIO-BMSC vs UL-BMSC 1, 7, 14 d NR NR NR (+) Liu et al [47 ] NSC XNG NR IC-CTL 3 × 104 5 Stroke + NSC_FA > Stroke + NSC 1, 7 d NR NR (+) Sox-2 BrdU at 21 d (+) Wang et al [48 ] MSC XNG 7d IC-CTL 1 × 105 5 FMNC-MSC > UL-MSC vs control (FMNC) 0, 1, 7, 30 d NR NR (+) TuJ1 (+) Lee et al [50 ] MSC XNG 48 IC-CTL 2 × 104 5 M600-MSC vs FC-MSC 1, 5, 12 d NR NR NR (+) MSC XNG 48 IV-tail 2 × 106 500 M600-MSC vs control 5, 12 d NR NR NR (+) Song et al [49 ] NPC XNG 24 IC-IPS 4 × 105 5 FO-NPC vs control 1, 3, 7, 14, 21, 28 d NR NR (+) BrdU; GFAP at 28 d (+) NPC XNG 24 IV-tail 4 × 106 500 FO-NPC vs control 1, 3, 7, 14, 21, 28 d NR NR (+) BrdU; GFAP at 28 d (+) Kim et al [51 ] MSC AuTL 7d IC-IPS/CTL 1 × 105 2 Feridex® -labeled hMSC over time for both vias 2d, 1, 2, 4, 6, 8, 10 wk NR NR (-) GFAP; TH; MAP2; TuJ1; Nestin at 10 wk (+) Guzman et al [52 ] NSC XNG 7d IC-CTL 3 × 105 /5 × 104 NSC-SCns-SPION 3, 9, 12,18 wk NR NR (+) SC121 or SC101; TuJ1; GFAP; MAP2 at 18 wk (+) Syková et al [53 ] rOEC ALG NR IC-CTL NR NR OEC-SPION over time 3-7 wk NR NR (+) NeuN; GFAP at 28 d (+) MSC XNG NR IV-femoral NR NR MSC over time 6-30 d NR NR (+) NeuN; GFAP at 28 d (+) Zhu et al [54 ] NSC AuTL NR IC NR NR Patients treat with NSC and no treat 2 yr (+) SEP and DRS at 6, 9 mo (+) cells uptake by PET at 3, 6 mo NI (+)