Exosomes are thought to promote brain restoration and induce reparative effects, including neurovascular remodeling and anti-apoptosis and anti-inflammatory effects. Recent reports have focused on the clinical application of exosomes as a possible method of drug delivery. NSC exosomes have been shown to improve function and reduce infarct volume more than MSC exosomes, which has been associated with a stronger effect in polarizing macrophages towards the M2 phenotype and inhibiting inflammation. The basic principle of exosome targeting is to fuse a specific peptide that originates in tissues or cells with proteins in the exosome membrane, such as the Lamp2b.
In several studies, exosome-mediated miRNA transfer has explained the interaction of the neurovascular unit (NVU) in brain remodeling and cerebral ischemic protection. They also confirmed that astrocyte exosomes treated with an OGD Sema-3A inhibitor further promoted neuronal axonal growth than normal astrocyte and OGD exosomes. In one study, exosomes loaded with rhodamine 123 were injected into zebrafish embryos and examined the fluorescence of rhodamine 123 in brain tissue. In addition, after a stroke, exosomes can also be synthesized and released from brain cells, which cross the blood-brain barrier (BBB), and can be detected in peripheral blood or cerebrospinal fluid. Priming with miR-132-3p enhances the effects of exosomes derived from mesenchymal stromal cells in improving ischemic brain injury.
Exosome biogenesis involves the formation of multivesicular bodies (MVB) from early endosomes, the production of intraluminal vesicles (ILV) in MVB, and transport and fusion with the plasma membrane to release ILVs from MVB. Exosomes derived from human mesenchymal stem cells alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and alleviating beta cell destruction. Compared to other techniques, NTA guarantees the original state of the exosomes and allows for faster detection. There was still a substantial amount of exosomes retained in the brain after intranasal administration, while an almost negligible amount after intravenous administration 24 hours after administration.
Intravenously injected GAPDH exosomes loaded with siRNA and fused with RVG specifically reduce GAPDH expression in the striatum, midbrain and cortex, but not in the liver, muscles, heart and other organs. Exosomes derived from human neural stem cells stimulated by interferon gamma improve therapeutic capacity in the ischemic stroke model. These modified exosomes were then loaded with exogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) short interfering RNA (siRNA) by electroporation.
