Table 1.
Characteristics of included studies.
| References | Country or region | Gender and species | Animal number | Comorbid status | Occlusion method | Occlusion time | Therapy time | Exosomes source | Administration method | Therapy dose | Measure time | Outcome measure |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Xin et al. (2017a) | USA | Male Wistar rats | T:24 C:8 E:8 |
Healthy | Filament insertion | 2 h | 24 h after operation | BMSCs | Intravenous administration | 100 μg | 1, 3, 7, 14, 21, and 28 days after stroke (C:8 and E:8 /timepoint) | 1. Behavioral tests (mNSS, Foot-fault test); 2. Axonal density, phosphorylated NF-H, synaptophysin; 3. Neurite branching, spine density; 4. NeuN/Brdu, NG2/Brdu, MBP/Brdu |
| Zhao et al. (2020) | China | Male SD rats | T:24 C:8 E:8 |
Healthy | Filament insertion | 90 min | 2 h after operation | BMSCs | Tail vein | 120 μg | 1, 3, and 7 days after stroke (C:8 and E:8 /timepoint) | 1. Behavioral tests (NSS, shuttle box test); 2. CD206 and CD86; 3. NO, IL-1β, TNF-α, IL-12, IL-10, TGF-β, BDNF, GDNF (ELISA, brain tissue). |
| Song et al. (2019) | China | Male ICR mice | T:48 C:8 E:8 |
Healthy | Filament insertion | 1 h | Immediately after operation | M2 microglia | Tail vein | 100μg/day,3 days | 3 days after stroke (C:8 and E:8) | 1. Infarct volumes (Cresyl Violet Staining); 2. Behavioral tests (mNSS); 3. Apoptosis (TUNEL) |
| Pei et al. (2019) | China | Male C57BL/6 mice | T:60 C:10 E:10 |
Healthy | Filament insertion | Permanent | 60 min after operation | Astrocytes | Tail vein | 80 μg | 3 days after stroke (C:10 and E:10) | 1. Infarct volumes (TTC); 2. Apoptosis (TUNEL); 3. GFAP, Iba-1; 4. Beclin-1, LC3-I/II, P62; 5. TNF-α, IL-6. IL-1β (ELISA, brain tissue). |
| Safakheil and Safakheil (2020) | Iran | MaleWistar rats | T:60 C:12 E:12 |
Healthy | Filament insertion | 60 min | 24 h after operation | BMSCs | Stereotaxic (brain cortex) | 100 μg | 24 h,7 days after stroke (C:12 and E:12 /timepoint) | 1. Behavioral tests (EBST, Garcia); 2. Infarct volume (TTC); 3. Dead cells (Cresyl Violet Staining); 4. NLRP1, NLRP3; 5. GFAP-positive cells; 6.MDA, SOD |
| Deng et al. (2019) | China | NRC57BL/6 mice | T:40 C:10 E:10 |
Healthy | Filament insertion | 30 min | NR | BMSCs | NR | NR | 4 weeks after treatment (C:10 and E:10) | 1. Infarct volumes (TTC); 2. Apoptosis (TUNEL); 3. LDH, cleaved caspase-3, Bax, Bcl-2; 4. IL-6, IL-1β, TNF-α (WB, brain tissue). |
| Jiang et al. (2018) | China | Male SD rats | T:24 C:6 E:6 |
Healthy | Filament insertion | Permanent | Immediately after operation | ADSCs | Tail vein | 80 μg | 3 h, 72 h after stroke (C:6 and E:6 /timepoint) | 1. Infarct volumes (TTC); 2. Apoptosis (TUNEL); 3. TNF-α, IL-6, IL-4, IL-10 (ELISA, serum). 4. CD206, iNOS, Beclin-1, Atg5, LC3 |
| Zheng et al. (2019) | China | Male SD rats | T:18 C:6 E:6 |
Healthy | Filament insertion | 2 h | Immediately after operation | Macrophages | Tail vein | 2 mg | 6 h (C:6 and E:6), 24 h after stroke (C:3 andE:3) | 1. Infarct volumes (TTC); 2. Behavioral tests (Zea-Longa, Ludmila Belayev); 3. CD 80, CD206, NeuN- positive cells; 4. IL-6, TNF-α, NF-κB p65 (WB, brain tissue). |
| Li et al. (2019) | China | Male C57BL/6 mice | T:42-48 C:14-16 E:14-16 |
Healthy | Bipolar electrocoat-gulation | Permanent | Immediately after operation | RIPC mice plasma | Tail vein | 10 μg/day,14 days | 24 h (C:14-16 and E:14-16) and 3, 7, 14, 21, 28 days after stroke (C:8-10 and E:8-10 /timepoint) | 1. Infarct volumes (TTC); 2. Behavioral tests (rotarod test, adhesive removal test); 3. HIF-1α |
| Li et al. (2019) | China | Male C57BL/6 mice | T:42-48 C:14-16 E:14-16 |
Healthy | Bipolar electrocoat-gulation | Permanent | Immediately after operation | Non-RIPC mice plasma | Tail vein | 10 μg/day,14 days | 24 h (C:14-16 and E:14-16) and 3, 7, 14, 21, and 28 days after stroke (C:8-10 and E:8-10 /timepoint) | 1. Infarct volumes (TTC); 2. Behavioral tests (rotarod test, adhesive removal test); 3. HIF-1α |
| Sun et al. (2019) | United States | Male CB57/B6 mice | T:30 C:15 E:15 |
Healthy | Filament insertion | 1 h | 2 h after operation | NSCs | Internal jugular vein | 10 μg | 24 h, 4 days after stroke (C:15 and E:15 /timepoint) | 1. Infarct volumes (TTC); 2. Behavioral tests (neurologic deficit score) |
| Nalamolu et al. (2019b) | USA | Male SD rats | T:30 C:15 E:15 |
Healthy | Filament insertion | 2 h | Immediately after operation | HUCB-MSCs | Tail vein | 150 μg | 1 (C:15 and E:15), 3, 5, and 7 days after stroke (C:9 and E:9 /timepoint) | 1. Infarct volumes (TTC); 2. Brain swelling; 3. Behavioral tests (mNSS, adhesive removal test, Beam-walking, Rotarod); 4. Body weight changes and mortality |
| Nalamolu et al. (2019a) | USA | Male SD rats | T:36 C:12 E:12 |
Healthy | Filament insertion | 2 h | Immediately after operation | Cocultures of normal and OGD-induced HUCB-MSCs | Tail vein | 150 μg | 1 (C:12 and E:12), 3 (C:10 and E:10), 5, and 7 days after stroke (C:8 and E:8 /timepoint) | 1. Infarct volumes (TTC); 2. Brain swelling; 3. Behavioral tests (mNSS, adhesive removal test, Beam-walking); 4. Body weight changes and mortality |
| Nalamolu et al. (2019a) | USA | Male SD rats | T:36 C:12 E:12 |
Healthy | Filament insertion | 2 h | Immediately after operation | OGD-induced HUCB-MSCs | Tail vein | 150 μg | 1 (C:12 and E:12), 3 (C:10 and E:10), 5, and 7 days after stroke (C:8 and E:8 /timepoint) | 1. Behavioral tests (mNSS, adhesive removal test, Beam-walking); 2. Body weight changes and mortality |
| Li G. et al. (2020) | China | Wild Balc/C mice | T:124 C:20 E:20 |
Healthy | Filament insertion | NR | Immediately after operation | hUCMSCs | Tail vein | 5 μg | 24 h after stroke (C:20 and E:20) | 1. Infarct volumes (TTC); 2. Brain edema; 3. Behavioral tests (Longa) |
| Li S. et al. (2020) | China | Wild Balc/C mice | T:124 C:20 E:20 |
Healthy | Filament insertion | NR | Immediately after operation | hUCMSCs | Tail vein | 50 μg | 24 h after stroke (C:20 and E:20) | 1. Infarct volumes (TTC); 2. Brain edema; 3. Behavioral tests (Longa); 4. TNF-?, IL-6, and CCL-2 (ELISA, brain tissue). 5. iNOS, Arg1, CD38+, CD206− |
| Chen K. H. et al. (2016) | Taiwan | Male SD rats | T:60 C:12 E:12 |
Healthy | Filament insertion | 50 min | 3 h after operation | Xenogenic ADMSCs | Intravenous administration | 100 μg | 1, 3, 14, 28, and 60 days after stroke (C:12 and E:12/timepoint) | 1. Infarct volumes (MRI); 2. Behavioral tests (Corner test); 3. MMP-9, IL-1β, TNF-α, RANTES, PAI-1, NF-κB and iNOS (WB, brain tissue). 4. NOX-1, NOX-2 and oxidized protein; 5. Cleaved caspase 3 and cleaved PARP, Smad3, TGF-β, Smad1/5 and BMP-2; 6. γ-H2AX, cytosolic cytochrome C, CD31, eNOS, VEGF, CXCR4; 7. CD11, CD68, XRCC1/CD90, p53BP1/CD90, GFAP, AQP4 |
| Ling et al. (2020) | China | Male SD rats | T:40 C:10 E:10 |
Healthy | Filament insertion | 2 h | 4 h after operation | hUSCs | Intravenous administration | 1 × 1011 particle | 1, 2, 3, 7, 14, 21, and 28 days after stroke (C:10 and E:10/timepoint) | 1. Infarct volumes (MRI/cresyl violet staining); 2. Behavioral tests (mNSS, foot-fault test); 3. EdU+/Nestin+, EdU+/Sox2+. |
| Xin et al. (2013a) | USA | Male Wistar rats | T:12 C:6 E:6 |
Healthy | Filament insertion | 2 h | 24 h after operation | BMSCs | Tail vein | 100 μg | 1, 3, 7, 14, 21, and 28 days after stroke (C:6 and E:6/timepoint) | 1. Infarct volumes (HE); 2. Behavioral tests (mNSS, Foot-fault test); 3. Axonal density, synaptophysin; 4. DCX/BrdU and vWF/Brdu |
| Venkat et al. (2019) | USA | male BKS.Cg-m+/+Leprdb /J mice | T:25 C:7 E:6 |
T2DM | Photothro-mbotic | Permanent | 3 days after operation | Mouse brain endothelial cells | Intravenous administration | 3 × 1010 | 1, 7, 14, 21, 25, 26, 27, and 28 days after stroke (C:7 and E:6/timepoint) | 1. Infarct volumes (HE); 2. Behavioral tests (adhesive removal test, novel odor recognition test); 3. Axon and Myelin Density, Vascular Density, Arterial Diameter, Vessel Patency; 4. ED1 and CD163 |
| Xin et al. (2017b) | USA | Male Wistar rats | T:24 C:6 E:6 |
Healthy | Filament insertion | 2 h | 24 h after operation | BMSCs | Intra-arterial administration | 100 μg | 1, 3, 7, 14, 21, and 28 days after stroke (C:6 and E:6/timepoint) | 1. Behavioral tests (mNSS, Foot-fault test); 2. Axonal density, synaptophysin, SMI-31 |
TTC, 2,3,5-triphenyl tetrazolium chloride; BMSCs, bone marrow mesenchymal stem cells; EBST, elevated body swing test; LDH, lactate dehydrogenase; NR, not reported; SD, Sprague-Dawley; C, control group; T, treatment group; ADSCs, adipose-derived stem cells; ADMSCs, adipose-derived mesenchymal stem cells; RIPC, remote ischemic pre-conditioning; NSCs, neural stem cells, HUCB-MSCs human umbilical cord blood-mesenchymal stem cells; mNSS, modified neurological severity scores; OGD, oxygen–glucose-deprived, hUCMSCs, human umbilical cord mesenchymal stem cells; hUSCs, human urine-derived stem cells; HE, hematoxylin and eosin; vWF, von Willebrand factor; T2DM, type 2 diabetes mellitus; BDNF, brain-derived neurotrophic factor; GDNF, glial cell-derived neurotrophic factor; TGF, transforming growth factor; ELISA, enzyme-linked immunosorbent assay; WB Western blot analysis; T, total animal in this study; C, control group; E, exosomes treatment group; TUNEL, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling.