Encapsulation of bryostatin-1 by targeted exosomes enhances remyelination and neuroprotection effects in the cuprizone-induced demyelinating animal model of multiple sclerosis

Abstract

Demyelinating disease is a critical neurological disease, and there is still a lack of effective treatment methods. In the past two decades, stem cells have emerged as a novel therapeutic...

High-efficiency brain-targeted intranasal delivery of BDNF mediated by engineered exosomes to promote remyelination

“…Upon CPZ withdrawal, myelination can be repaired gradually. 41,42 Therefore, CPZ mice have been widely used in the study of demyelination and remyelination in MS. 20 A CPZ mouse model was constructed by feeding a mouse with rodent chow containing 0.2% CPZ for 6 weeks to induce complete demyelination. Then, the mouse was fed with a normal diet and checked for the demyelination of the corpus callosum (Fig.…”

“…Previous studies have proved that BDNF can promote the proliferation of OPCs. 17–20 In this study, the effect of engineered exosome-mediated BDNF on OPCs in the corpus callosum of CPZ model mice was studied by PDGFRα immunofluorescence staining. The results indicated that RVG/BDNF-Exo significantly promoted the increase in the number of PDGFRα + OPCs in the corpus callosum region, which plays a positive role in remyelination (Fig.…”

“…Intravenously administered exosomes can enter the brain through the BBB, even though most of the exosomes are still taken up by the liver, while brain-targeted modifications of exosomes can significantly increase their chance of entering the brain. 19,20 The rabies virus glycoprotein (RVG) peptide can specifically bind to the acetylcholine receptor (nAchR) expressed by neurons. 21,22 RVG peptide-modified exosomes have brain targeting effects and can enhance drug delivery and treatment efficiency in CNS diseases after intravenous administration.…”

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

“…Exosomes derived from neural stem cells were targeted using a lentivirus-armed PDGFR-alpha ligand capable of anchoring the membrane [ 116 ]. Exosomes modified in this manner appeared to be capable of targeting oligodendrocyte progenitor cells in the neural lesion area.…”

“…This novel exosome-based delivery method significantly enhanced the myelin sheath’s ability to protect integrity and promote remyelination. Additionally, it inhibited astrogliosis and axon damage as well as pro-inflammatory microglia [ 116 ].…”