(N32) Deferoxamine-preconditioned cAT-msc-derived Extracellular Vesicles Alleviate Inflammation in an EAE Mouse Model Through STAT3 Regulation

Abstract:

Background: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have been investigated as a treatment option for autoimmune diseases. Hypoxic stimulation is a strategy to improve the function of MSC-derived EVs.

Methods: DFO, an iron chelator, was used to induce hypoxic conditions. The cAT-MSCs were cultured with DFO for 48 h and EVs were isolated from culture media. EAE mice were divided into different groups based on intranasal administration of EVs or EVDFO. On day 25 post-EAE induction, the mice were euthanized, and the spleen, brain, and spinal cord were analyzed into histopathologic and expression of RNA and protein level.

Results: EVDFO administration resulted in a significant treatment effect in the EAE model. Histologically, in the EV and EVDFO groups, the infiltration of inflammatory cells decreased significantly, and demyelination was alleviated. Immunofluorescence staining showed that the expression of CD206 and Foxp3, markers of M2 macrophages and regulatory T (Treg) cells, respectively, increased significantly in the EVDFO group compared to the EAE and EAE+EV groups. Also, the number of CD4+CD25+Foxp3+ Treg cells in the spleen showed a greater increase in the EAE+EVDFO group than in the EAE+EV group. Following EV treatment, STAT3 expression of brain and spleen decreased compared to the EAE group,

Conclusions: EVDFO treatment has a relatively higher efficacy in reducing inflammation than non-preconditioned EV treatment. Moreover, our findings suggest that STAT3 regulation may play a major role in regulating T cells and that EVDFO can control the STAT3 pathway.