Table 3.
The Immunosuppressive Effect of Pretreated MSCs and Extracellular Vesicles Secreted by MSCs in SCI
| Source | Pretreatment | Dose (Number) | Model | Way | Infusion time | Secretion of MSCs | Immunomodulatory Mechanism | Effect | Refs. |
|---|---|---|---|---|---|---|---|---|---|
| Human umbilical cord | Hypoxia | 1×105 | Rat | Intralesional | N/A | N/A | Up-regulate the levels of regenerative neurotrophic factors, inhibit microglial/macrophage infiltration | Promote functional recovery | [184] |
| Human gingiva | Vesicular moringin nanostructures | 1×106 | Mice | Intravenous | 1h hour after SCI | N/A | Increase the levels of anti‐inflammatory cytokines such as IL‐10 and TGF‐β | Promote functional recovery | [185] |
| Rat bone marrow | Hypoxia | 1×106 | Rat | Intralesional | The day following SCI | N/A | Down-regulate the levels of pro‐inflammatory cytokines such as TNF-α, IL-1β and IL-6 | Improve motor and sensory function | [186] |
| Human umbilical cord | N/A | 1, 2, 3ug | Rat | Intrathecal | 24 h after SCI | EVs | Decrease the expression of caspase-1, IL-1, IL-18 and TNF-α | Improve locomotor function | [187] |
| Human umbilical cord | N/A | 25μg | Mice | Intravenous | 1 h and 7 days after SCI | N-NVs | N-NVs shift the balance from M1 to M2 macrophages | Promote functional recovery | [142] |
| Rat bone marrow | Hypoxia | 200μg | Mice | Intravenous | The day following SCI | Exosome | Promote microglia/macrophage polarization from M1 to M2 phenotype, inhibit the TLR4 pathway | Promote functional recovery | [188] |
| Rat bone marrow | N/A | 2.5×109 | Rat | Intravenous | 1 week after SCI | Exosome | Increase the production of anti-inflammatory cytokines, block M2 macrophages from converting to an M1 pro-inflammatory activation state | N/A | [189] |
| Rat bone marrow | N/A | N/A | Rat | Intravenous | 7 consecutive days after SCI | Exosome | Increase the expression levels of anti-inflammatory factors such as IL-10 and IL-4, decrease the levels of TNF-a, IL-1b and MCP-1 | Promote functional recovery | [190] |
| Human umbilical cord | Overexpression of NT-3 | 1×106 | Rat | Intralesional | 1 week after SCI | NT-3 | Reduce the accumulation of immunoreactive macrophages/microglia | Promote functional recovery | [191,192] |
| Mice bone marrow | Overexpression of IGF-1 | 1×106 | Mice | Intralesional | N/A | IGF-1 | Up-regulate antioxidant defense genes and the expression levels of Mrc1, Nfe2L2, reduce the levels of MDA, nitrite | Promote functional recovery | [193] |
| Rat bone marrow | N/A | 200μg | Rat | Intravenous | The day following SCI | Exosome | Suppress the activation of microglia and A1 astrocytes, decrease the levels of TNF-a, IL-1b and IL-6 | Promote functional recovery | [194] |
| Rat bone marrow | N/A | 40μg | Rat | Intravenous | 30 minutes after SCI | Exosome | Reduce the proportion of A1 astrocytes and the levels of TNF-α, IL-1α and IL-1β | Promote functional recovery | [161] |
Abbreviations: EVs, extracellular vehicles; N-NVs, normal MSC-derived nanovesicles; NT-3, neurotrophin-3; IGF-1, insulin-like growth factor 1; Mrc1, recombinant mannose receptor C type 1; Nfe2L2, recombinant nuclear factor erythroid 2 like protein 2; MDA, malondialdehyde; N/A, not applicable.