Table 1.
Some MSC derived EVs as potential therapy for neurodegenerative diseases
| Source of MSC-EVs | Disease / Conditions | In vitro model | In vivo model | Molecular mechanism | Therapeutic application | References |
|---|---|---|---|---|---|---|
| Bone marrow | AD | APP/PS1 mice and their non-transgenic littermates | EVs from MSCs affected iNOS expression by lowering Aβ levels | Enhanced synaptic plasticity and cognitive performance in a mouse model of AD. | 182 | |
| bone marrow | AD | AD Rat model | BACE1 was targeted by miR-29c-3p, which activated the Wnt/β-catenin pathway | Wnt/β-catenin pathway inhibition impaired EV therapeutic effects on AD | 183 | |
| bone marrow | AD | APPswe/PS1dE9 AD mice | BM-MSC-EVs are effective at reducing the Aβ plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. | The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct β-amyloid degrading action. | 184 | |
| bone marrow | AD | C57BL/6 mice | NLRP3-activated inflammasomes and mitochondrial damage-associated apoptosis in neuronal cells were significantly reduced by MSC-EVs-SHP2 | EV-engineering can be used to induce mitophagy in AD patients, providing an effective treatment option | 186 | |
| bone marrow | AD | Microglial cells | Triple-transgenic AD mice (3xTg-AD) | MSC-EVs induced dendritic spine density in the brain and dampened microglia activation. | MSC-EVs might be able to be administered in a non-invasive way and demonstrate anti-inflammatory properties, which could enhance their translational potential in AD | 187 |
| bone marrow | AD | Microglial cells | MSC-EVs prevented proinflammatory mediators from gaining influence, such as tumor necrosis factor (TNF)-α and nitric oxide (NO). | The use of MSC-EVs as a promising therapeutic tool to treat neuroinflammatory diseases | 188 | |
| Human umbilical cord | Ischemic stroke | bend.3 cell line | C57BL/6 N mice | By inhibiting tPA-induced astrocyte activation and inflammation, MSC-EVs also attenuated disruption of the BBB. | MSC-EVs were found to be non-invasive thrombolytic adjuvants following tPA treatment for ischemic strokes | 169 |
| Human umbilical cord | AD | SH-SY5Y cells | hucMSC-EVs were significantly dephosphorylated at Thr181 (p181-tau), which is elevated in AD. SH-SY5Y cells were also reduced in oxidative stress by hucMSC-EVs after being treated with OA | Novel approach for treating AD with MSC-EVs with abundant mitochondria | 189 | |
| bone marrow | ALS | Mouse SOD1G93A astrocytes and iAstrocytes | B6SJL-TgN SOD1/G93A1Gur mice | Argocytes' reactive phenotype and neurotoxicity are modulated by MSC-EVs' anti-inflammatory and antioxidant-shuttled miRNAs, which represents a therapeutic strategy in ALS | MSC-EVs may be therapeutically effective across different subtypes of ALS, beyond SOD1 as a model. | 190 |
| hMSCs | AD | HMC3 cells | Male C57BL/6 mice | EVs from MSC inhibited microglia and astrocyte activation, amyloid deposition, demyelination, memory loss, and anxiety-like behavior more than non-MSC EVs. | MiRNAs released by MSC enhanced immunity regulation when combined with activation microglia secretomes | 191 |
| bone marrow | Status epilepticus (SE) | Male C57BL/6J mice | MSC-EVs reached the hippocampus and decreased glutamatergic and GABAergic neuron loss and inflammation | MSC-EV administration helps prevent SE-induced memory impairment and reduces cognitive impairment due to SE in the hippocampus, according to these results | 192 | |
| Human ADMSCs | Multiple sclerosis | Female SJL/J mice | A significant reduction in plasma cytokine levels is observed in TMEV mice treated with EVs, mainly in Th1 and Th17 phenotypes, confirming EVs' immunomodulatory potential | he effects of EV administration on motor deficits were observed as a result of reduced brain atrophy and promoting remyelination through immunomodulatory effects | 193 | |
| bone marrow | Neuroinflammation | Murine microglial cell line N9 | B6SJL-TgN SOD1/G93A1Gur mice | In activated N9 microglia cells, as well as in primary microglia isolated from ALS-prone SOD1G93A mice, miR-467f and miR-466q have been shown to downregulate TNF and Il1b expression. | MSC-EVs manipulate neuroinflammation by modulating the immune response mediated by microglia | 194 |
| chorionic villus tissue | MS | SH-SY5Y neuroblastoma cell line | C57BL/6J mice | MSC-EVs stimulate the differentiation of endogenous oligodendrocyte precursors into mature myelinating oligodendrocytes to promote myelin regeneration | They have shown potential in animal models of MS as an alternative to cell-based therapies | 195 |
| bone marrow | hypoxia-ischemia (HI) | C57BL/6 mice | A significant reduction in TNFa expression occurs when MSC-EVs are used, while an increase in YM-1 and TGFb expression occurs when MSC-EVs are used. | Neonatal brain injury may benefit from MSC-EV treatment instead of risk-associated cell therapies | 196 | |
| bone marrow | AD | 5XFAD mice and NT mice | hMSC-EVs treated 5XFAD mice performed significantly better than those treated with saline. Hippocampus plaque loads were also reduced in mice treated with hMSC-EV | MSC EVs could have a beneficial effect on AD progression | 197 |