Therapeutic Effect of Human Amniotic Epithelial Cells in Murine Models of Hashimoto's Thyroiditis and Systemic Lupus Erythematosus

Background Aims: The chronic inflammation of autoimmune diseases develops repetitive localized destruction or systemic disorders, represented by Hashimoto's thyroiditis (HT) and Systemic lupus erythematosus (SLE) respectively. Currently, there are no efficient ways to treat these autoimmune diseases. Therefore, it is critically important to explore new therapeutic strategies. The aim of this study was to investigate the therapeutic efficacy of human amniotic epithelial cells (hAECs) in murine models of HT and SLE.

Methods: Experimental autoimmune thyroiditis (EAT) was induced in female CBA/J mice by immunization with porcine thyroglobulin (pTg). hAECs were intravenously administered at different time points during the disease course. MRL-Fas mice, a strain with spontaneously occurring SLE, were intravenously administered hAECs when their sera were positive for both anti-nuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies. Two weeks after the last cell transplantation, blood and tissue samples were collected for histological examination and immune system analysis.

Results: hAECs prevented lymphocytes infiltration into the thyroid and improved the damage of thyroid follicular in EAT mice. Correspondingly, hAECs administration reduced anti-thyroglobulin antibodies (TGAb), anti-thyroid peroxidase antibodies (TPOAb) and thyroid stimulating hormone (TSH) levels. SLE mice injected with hAECs appeared negative for ANAs and anti-dsDNA antibodies and showed reduced immunoglobulin profiles. Mechanically, hAECs modulated the immune cells balance in EAT and SLE mice, by downregulating the ratios of Th17/Treg cells in both EAT and SLE mice and upregulating the proportion of B10 cells in EAT mice. This was confirmed by in vitro assay, in which hAECs inhibited the activation of EAT mice-derived splenocytes. Moreover, hAECs improved the cytokine environment in both EAT and SLE mice, by suppressing the levels of IL-17A and IFN-γ and enhancing TGF-β.

Conclusion: These results demonstrated the immunoregulatory effect of hAECs for inflammation inhibition and injury recovery in HT and SLE murine models. The current study may provide a novel therapeutic strategy for these autoimmune diseases in clinic.