Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score.

Mesenchymal stem cell-derived exosome is a safe and effective delivery platform with a potential capacity to exert immunomodulation effect and peripheral tolerance toward auto-reactive cells via bearing regulatory and tolerogenic molecules. Inflammation and neurodegeneration are the clinical manifestation of multiple sclerosis (MS). In order to fight against MS, the efficient choices are the ones, which prevent inflammation and induce remyelination. In this regard, the previously reported LJM-3064 aptamer which showed considerable affinity toward myelin and demonstrated remyelination induction was employed as both targeting ligand and therapeutic agent. Thus, in the current study, the carboxylic acid-functionalized LJM-3064 aptamer was covalently conjugated to the amine groups on the exosome surface through EDC/NHS chemistry. The obtained results showed that the aptamer-exosome bioconjugate could promote the proliferation of oligodendroglia cell line (OLN93) in vitro. Moreover, in vivo administration of the prepared aptamer-exosome bioconjugate in female C57BL/6 mice as a prophylactic measure produced a robust suppression of inflammatory response as well as lowered demyelination lesion region in CNS, resulting in reduced in vivo severity of the disease. The prepared platform employing exosome-based nanomedicine as a novel approach for managing MS would hopefully pave the way to introduce a versatile approach toward an effective clinical reality.