Experimental autoimmune encephalomyelitis reduces the immunomodulatory properties of mesenchymal stem cells

Abstract

Abstract Introduction: The impact of disease conditions on the differentiation capability of mesenchymal stem cells (MSCs) has been studied well. However, how disease-related alterations in MSCs affect the immune response has not been reported. Materials & Methods: MSCs were isolated from adipose tissue of healthy and experimental autoimmune encephalomyelitis (EAE) mice and cultured in DMEM media with or without lipopolysaccharides (LPS, 10 ng/mL) preconditioning. The effects of MSC-conditioned media (CM) on the recall responses of splenocytes isolated from EAE mice were evaluated in vitro. Results: MSCs obtained from healthy mice produced more IL-10 than those isolated from EAE mice, but no difference in TGF-β production was observed. The expression of Foxp3 and Gata3 transcription factors, as well as IL-10 and NO levels in the splenocytes of EAE mice that were treated with MSC-CM of EAE mice, were significantly lower than in cells treated with MSC-CM of healthy mice. Moreover, results showed that the mRNA level of RORγt and production of IL-17a by splenocytes of EAE mice after treatment with MSC-CM of EAE mice was significantly higher in comparison to splenocytes that were treated with healthy MSC-CM. However, the mRNA expression level of T-bet and the concentration of IFN-γ were statistically similar in splenocyte culture after treatment with MSC-CM of healthy and EAE mice. Conclusion: Results revealed that MSCs of EAE mice had a lower ability to upregulate Foxp3 mRNA and down-modulate recall immune responses of EAE splenocytes that were restimulated with MOG35-55 than healthy MSCs.