Table 6.
Summary of therapeutic efficacy and safety of MSC-secretome and EVs in preclinical animal models of MS.
| Study | Animal model | Therapeutic agent | Route and dosage | Main outcomes |
|---|---|---|---|---|
| Rajan et al. [116] | Male C57BL/6 mice (12 weeks old) treated with MOG35-55 | Secretome or EVs from hPDL-MSCs | Injection via tail vein | Immunosuppressive action. |
| NALP3 inflammasome inactivation. | ||||
| NF-κB reduction. | ||||
| These effects were exerted both by secretome and EVs. | ||||
| Farinazzo et al. [117] | C57BL/6 mice (6–8 weeks old) treated with MOG35-55 | EVs from mA-MSCs | Intravenous injection of 5 μg of EVs | Reduction of spinal cord inflammation and demyelination. |
| Marginal inhibition of antigen-specific T cell activation. | ||||
| Reduction of microglial activation. | ||||
| Reduction of demyelination in the spinal cord. | ||||
| Clark et al. [118] | Male and female C57BL/6J mice (3 months old) treated with MOG35-55 | EVs from hP- MSCs | Injection via tail vein of 1 × 107 or 1 × 1010 EVs | Improvement of motor function outcomes. |
| Improvement of symptoms. | ||||
| Reduction of DNA damage in oligodendroglia populations. | ||||
| Increase of myelination within the spinal cord. | ||||
| Li et al. [124] | Female rats immunized with guinea pig spinal cord homogenate + Freund's adjuvant containing Mycobacterium tuberculosis H37Ra | EVs from rBM-MSCs | Injection via tail vein of 100 μg or 400 μg of EVs | Decrease of neural behavioral scores. |
| Reduction of inflammatory cell infiltration into the CNS. | ||||
| Regulation of microglia polarization. | ||||
| Decrease of demyelination. | ||||
| Increase IL-10 and TGF-β levels. | ||||
| Reduction of TNF-α and IL-12 levels. | ||||
| Shamili et al. [119] | Female C57BL/6 mice (10–13 weeks) treated with MOG35-55 | EVs from mBM-MSCs conjugated with carboxylic acid-functionalized LJM-3064 aptamer | Intravenous injection of 200 μg of EVs | Reduction of the severity of the disease. |
| Suppression of the inflammatory response. | ||||
| Reduction of demyelination. | ||||
| Jafarinia et al. [120] | C57BL/6 mice (6–8 weeks old) treated with MOG35-55 | EVs from hA-MSCs | Intravenous injection of 60 μgof EVs | Decrease of the maximum mean clinical score. |
| Reduction of inflammation scores. | ||||
| Reduction of the percentage of demyelination areas. | ||||
| Fathollahi et al. [121] | Female C57BL/6 mice (6–8 weeks old) treated with MOG35-55 | EVs from mA-MSCs | Intranasal administration of 10 μg of EVs | Decrease the clinical symptoms. |
| Increase in immunomodulatory responses. | ||||
| Increase of TGF-β levels. | ||||
| Koohsari et al. [122] | Female C57BL/6 mice (6–8 weeks old) treated with MOG35-55 | EVs from hUC-MSCs | Intravenous injection | Reduction of pro-inflammatory cytokines (IL-17a, TNF-α, and IFN-γ). |
| Increase of the anti-inflammatory cytokines (IL-4 and IL-10). | ||||
| Decrease of leukocyte infiltration. | ||||
| Improvement of body weight. | ||||
| Zhang et al. [123] | Female C57BL/6 mice (6–8 weeks old) treated with MOG35-55 | EVs from moMSCs | Injection via tail vein of 5 × 1010 EVs | Improvement of neurological outcome. |
| Increase of myelin basic protein. | ||||
| Decrease of neuroinflammation. | ||||
| Modulation of microglia activation. | ||||
| Modulation of cytokine levels. |
MOG35-55 = oligodendrocyte glycoprotein peptide.
h = human; m = mouse; mo = monkey.
PDL = periodontal ligament; A = adipose; P = placenta; BM = bone marrow; UC = umbilical cord.