Ary hypertension, indicating that MSC-derived EVs exert equivalent effects as MSCs [648]. As a consequence of their high stability inside the bloodstream as well as the capacity to penetrate blood-brain barrier (BBB), MSC-derived EVs possess a excellent possible for the remedy of neurological and neurodegenerative GS-626510 Epigenetics diseases, which has been experimentally confirmed as EVs administration by way of each intravenous and intranasal routes [25,692]. Furthermore, an inflammatory state in AD or Parkinson’s disease (PD) makes the BBB far more vulnerable to facilitate EVs transport from the peripheral circulation to the brain [735]. Consequently, it could reasonably be anticipated that MSC-derived EVs manifest advantageous effects in AD treatments. MSC-derived EVs have shown promise in improving the cognitive deficits induced by A12 aggregates and promoting neurogenesis in the hippocampus and subventricular zone (SVZ), that are of excellent significance inside the transition from short-term memory to long-term memory [70,76]. In vitro final results have addressed that MSC-derived EVs safeguard neurons from oxidative tension and synapse harm induced by A oligomers [77,78]. Wang et al. and our lab demonstrated the optimistic effect of employing MSC-derived EVs (BMMSCs and WJ-MSCs, respectively) each in vitro and in vivo [71,79]. BM-MSC-derived EVs considerably decreased As induced inducible nitric oxide synthase (iNOS) expression in cultured main neurons. Administration of BM-MSC-derived EVs intracerebroventricularly was shown to enhance cognitive behavior, rescue synaptic transmission in hippocampal CA1 regions and long-term potentiation (LTP) in APP/PS1 Thromboxane B2 MedChemExpress transgenic mice. In our analysis, the human neuroblastoma cell line overexpressing FAD mutations and J20 transgenic mice have been utilized to investigate the therapeutic effect of WJ-MSC-derived EVs. Reduced A expression and restored expression of neuronal memory/synaptic plasticity-related genes had been observed in the cell model. In vivo studies demonstrated enhanced cognitive function, restored glucose metabolism, and inhibited astrocytes/microglia activation in mice that had been administrated with WJ-MSC-derived EVs via an intravenous injection [71]. Moreover, an option delivery of MSC-derived EVs for therapeutic intervention in AD by means of the intranasal route has been used in recent research owing to the safety, lowMembranes 2021, 11,5 ofinvasive procedure plus a larger amount of EVs reaching the brain [70,80,81]. Similarly, MSC-derived EVs exhibit neuroprotective and immunomodulatory potential, evidenced by elevated dendritic spine density and decreased microglia activation in treated mice [80]. An additional current study has demonstrated that MSC-derived EVs can lower A plaque burden and reduce the colocalization involving A plaque and glial fibrillary acidic protein (GFAP, a reactive astrocyte marker) in the brain [81]. The therapeutic effects of MSC-derived EVs obtained from the cell and animal models of AD are summarized in Table 1.Table 1. A summary of preclinical research of MSC-derived EVs-based therapy each in vitro and in vivo models of AD. Model Supply of EVs Protocol Administration Route Reported Effects Ref.In vitro models Decreased extracellular and intracellular As levels Decreased extracellular and intracellular As levels Decreased As expression and restored the expression of neuronal memory/synaptic plasticity-related genes Lowered A levels along with the A 42/40 ratio, enhanced neurite development and alleviated cell apoptosis Decreased As induced iNOS expre.
