Aptamer Conjugated MSC-Derived Exosomes for In-ducing Remyelination in Multiple Sclerosis Model

Background: One of the well-known classes of secreted bio-logical nanovesicles are exosomes, released by various cells. Some studies indicated that multiple sclerosis (MSC) secretome could be a capable therapeutic agent for the inflammatory and degenerative diseases such as MS and rheumatoid arthritis.Materials and Methods: In the current study, we isolated and implemented the exosomes-derived MSC as a potent carrier to deliver therapeutic LJM-3064 aptamer. In this regard, the carboxylic acid-functionalized LJM-3064 aptamer was cova-lently conjugated to the amine groups on the exosome surface through EDC/NHS chemistry. Then the effects of MSC-derived exsosomes decorated with LJM-3064 aptamer (Exo-APT) was evaluated on remeylination processes and immunomodulatory activity in myelin oligodendrocyte glycoprotein (MOG35-55)-induced mouse MS model (EAE).Results: Our results demonstrated that surface functionaliza-tion of exosomes with LJM-3064 aptamer produced synergistic immunomodulatory properties and remyelination effect.In this regard, it was confirmed that prophylactic administra-tion of Exo-APT significantly decreased the ameliorating dis-ease severity by reducing Th1 response and increasing Treg population leading to the lowest inflammation and recruitment of inflammatory cells into the CNS. The obtained results were further supported by significant reduction in demyelination and pathological scores.Conclusion: The prepared platform employing exosome-based nanomedicine as a novel approach for managing MS would hopefully pave the way to introduce a versatile approach to-ward an effective clinical reality.

کلیدواژه ها:

Multiple Sclerosis (MS) ، Mesenchymal Stem Cell ، Exosome ، Aptamer