Effects of Dexamethasone and Tacrolimus on Mesenchymal Stem Cell Characteristics and Gene Expression

Mesenchymal stem cells (MSCs) are frequently used for therapeutic applications in both pre-clinical and clinical settings owing to their capacity for immune modulation and neuroprotective effects. However, transient fever is commonly observed as an adverse event following MSC injection in patients with Alzheimer's disease (AD). In this study, we investigated the potential impact of immunosuppressants such as dexamethasone and tacrolimus on altering the characteristics of human mesenchymal stem cells (hMSCs). Additionally, we examined whether these immunosuppressants affect the persistence of hMSCs or the immune response upon their administration into the brain parenchyma of AD mice. The exposure of hMSCs to high concentrations of dexamethasone and tacrolimus <i>in vitro</i> did not significantly alter the characteristics of hMSCs. The expression of genes related to innate immune responses, such as <i>Irak1, Irf3, Nod1</i>, and <i>Ifnar1</i>, was significantly downregulated by the additional administration of dexamethasone and tacrolimus to the brain parenchyma of AD mice. However, hMSC persistence in the AD mouse brain was not affected. The results of this study support the use of immunosuppressants to mitigate fever during stem cell therapy in patients with AD.