Prior dexamethasone exposure attenuates the therapeutic efficacy of mouse bone marrow-derived mesenchymal stem cells in experimental autoimmune encephalomyelitis by fostering a hostile immunological microenvironment

Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for treating autoimmune diseases like multiple sclerosis (MS) due to their ability to differentiate into multiple lineages and their immunomodulatory properties. However, the immunomodulatory capacity of BMSCs is highly adaptable, and primarily regulated by inflammatory factors. In this study, we evaluated the therapeutic effectiveness of BMSCs in dexamethasone (DEX)-pretreated experimental autoimmune encephalomyelitis (EAE) mice. Our results demonstrated a significant interaction between DEX and BMSCs. In contrast to their effect in non-pretreated mice, BMSCs administration in DEX-pretreated EAE mice resulted in a significant increase in infiltrating CD4⁺ T cells and a concomitant decrease in regulatory T (Treg) cell populations in the central nerves system, which likely resulted from DEX-induced changes in the peripheral immune microenvironment. Our findings in the EAE model indicate that the immune microenvironment established by DEX pretreatment is detrimental to the efficacy of BMSC therapy. This preclinical evidence suggests that evaluating the peripheral immune status may be a critical consideration for future clinical studies of MSC treatment in MS.