Table 1.
Recent research on the use of naïve extracellular vesicles (EVs) for treatment of ischemic stroke (IS).
| EV Source | Major Cargo Molecules |
In Vitro Stroke Model | In Vivo Stroke Model | Major Targeted Molecules/Pathway | Outcome | Reference | |||
|---|---|---|---|---|---|---|---|---|---|
| Animal Model | Administration Route | Dosage | Time Point of Administration | ||||||
| Rat BM-MSCs | - | - | Rat tMCAO model (2 h) | Tail vein | 100 μg | 24 h | - | Enhanced neurite remodeling Enhanced neurogenesis and angiogenesis |
[23] |
| Human iPSC-derived MSCs | - | OGD/R-HUVECs (8 h) | Rat tMCAO model (2 h) | Tail vein | 1 × 1011 particles | 4 h | STAT3 | Enhanced angiogenesis Reduced autophagy |
[24] |
| HUVECs | miR-1290 | OGD/R-neurons (1.5 h) | Mouse tMCAO model (1 h) | Intracranial (AP: 2.0 mm, ML: 1.7 mm, DV: 1.35 mm) |
5 μg | Immediately (0 h) |
- | Reduced apoptosis | [25] |
| Human NSCs | - | Glucose-free H/R model (1.5 h) | - | - | - | - | - | Reduced apoptosis and oxidative stress Enhanced axonal elongation Enhanced angiogenesis |
[32] |
| Rat BM-MSCs | - | OGD/R-microglia (1–5 h) | Rat tMCAO model (1.5 h) | Tail vein | 120 μg | 2 h | cysLT2R ERK1/2 |
Mitigated microglia M1 polarization | [33] |
| Human BM-MSCs | - | - | Mouse tMCAO model (0.5 h) | Tail vein | Released by 2 × 106 MSCs | Immediately (0 h) |
- | Reduced apoptosis Reduced peripheral immune cell inflitration |
[34] |
| Astrocytes | miR-34c | OGD/R-N2a cells (-) | Rat tMCAO model (-) | Tail vein | - | - | TLR7 NF-κB/MAPK pathway |
Reduced apoptosis and inflammation | [35] |
| Human ESCs | TGF-β and Smad2 and Smad4 |
- | Mouse tMCAO model (1 h) | Tail vein | 1 × 109 particles | 2 h and day 1, 2 (3 times) |
TGF-β/Smad pathway | Reduced apoptosis and inflammation Reduced peripheral immune cell inflitration |
[36] |
| UC-MSCs | circBBS2 | H/R model of SH-SY5Y cells (4 h) | Rat tMCAO model (2 h) | Tail vein | 50 μg | 4 h and day 1, 2 (3 times) |
miR-494 | Reduced ferroptosis by upregulation of SLC7A11 | [37] |
| Mouse AD-MSCs | miR-760-3p | OGD/R-N2a cells (4 h) | Mouse tMCAO model (1 h) | Intranasal | 10 μg | Day 1, 3, 5 (3 times) |
CHAC1 | Reduced ferroptosis | [38] |
| Rat BM-MSCs | - | OGD/R-BV2 and PC12 cells (6 h) | Rat tMCAO model (2 h) | Tail vein | 80 μg (low) 100 μg (medium) 120 μg (high) |
2 h | - | Shift of microglial polarization state toward M2 phenotype Reduced pyroptosis and inflammation |
[39] |
| Mouse AD-MSCs | miR-25-3p | OGD/R-neurons (10 h) | Mouse tMCAO model (1 h) | Femoral vein | 10 μg | Immediately (0 h) or 12 h |
p53-BNIP3 signaling | Reduced autophagy | [40] |
| Human BM-MSCs | - | - | Mouse tMCAO model (0.5 h) | Femoral vein | EVs released by 2 × 106 MSCs | Day 1, 3, 5 (3 times) |
- | Neuroprotection Enhanced neurogenesis and angiogenesis Modulated peripheral immune response |
[41] |