Bing Tan1, Weixin Yuan1, Jinying Li1, Pengjie Yang1, Zhen Ge2, Jia Liu1, Chen Qiu1, Xiaolong Zhu1, Cong Qiu1, Dongmei Lai3, Lihe Guo4, Liang Wang5, Luyang Yu6. 1. Institute of Genetics and Regenerative Biology, College of Life Sciences, Hangzhou, China; College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Hangzhou, China; Center for Stem Cell and Regenerative Medicine, Hangzhou, China. 2. Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, China. 3. International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China. 4. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai iCELL Biotechnology Co Ltd, Shanghai 200333, China. 5. Center for Stem Cell and Regenerative Medicine, Hangzhou, China; The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: 2196042@zju.edu.cn. 6. Institute of Genetics and Regenerative Biology, College of Life Sciences, Hangzhou, China; College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Hangzhou, China; Center for Stem Cell and Regenerative Medicine, Hangzhou, China. Electronic address: luyangyu@zju.edu.cn.
Abstract
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-Faslpr 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.
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-Faslpr 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. SLEmice 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 SLEmice, by downregulating the ratios of Th17/Treg cells in both EAT and SLEmice 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 SLEmice, 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 SLEmurine models. The current study may provide a novel therapeutic strategy for these autoimmune diseases in clinic.
Authors: Marta Magatti; Alice Masserdotti; Anna Cargnoni; Andrea Papait; Francesca Romana Stefani; Antonietta Rosa Silini; Ornella Parolini Journal: Int J Mol Sci Date: 2021-03-26 Impact factor: 5.923
Authors: Patrick Ming-Kuen Tang; Haiyong Chen; Ying Tang; David J Nikolic-Paterson; Hui Yao Lan Journal: Front Physiol Date: 2022-01-25 Impact factor: 4.566