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Transplantation of IFN-γ Primed hUCMSCs Significantly Improved Outcomes of Experimental Autoimmune Encephalomyelitis in a Mouse Model

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The aim of this study was to investigate potential therapeutic effects of IFN-γ primed human umbilical cord mesenchymal stem cell (IFN-γ-hUCMSCs) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. In this study, EAE mouse model was established by MOG35-55 immunization method. Outcomes of the EAE mice in terms of body weight and clinical symptoms were analyzed. Electromyography (EMG) was performed to evaluate nerve conduction. ELISA was applied to quantify inflammatory cytokine levels in serum. Our results showed that IFN-γ could up-regulate protein expression of indoleamine 2, 3-dioxygenease 1 (IDO1), an important molecule released by MSCs to exert their immune suppressive activity (p < 0.01). In this study treatment efficacy for EAE was compared between transplantation of hUCMSCs alone and the IFN-γ-hUCMSCs which were cultured in the presence of IFN-γ for 48 h prior to be harvested for transplantation. Compared with hUCMSCs alone and control (PBS transfusion) group, transplantation of the IFN-γ-hUCMSCs could significantly alleviate the body weight loss and clinical symptoms of EAE mice (p < 0.05). Consistently EMG latency was significantly improved in treatment groups (p < 0.001), and the IFN-γ-hUCMSCs group was even better than the hUCMSCs group (p < 0.05). Moreover, the concentrations of IL-17A and TNF-α in serum of the mice treated by IFN-γ-hUCMSCs were significantly lower than hUCMSCs alone and controls, respectively (p < 0.05). In few of the roles of IL-17A and TNF-α in the pathogenesis of EAE, IFN-γ-hUCMSCs treatment associated-suppression of IL-17A and TNF-α expression may contribute in part to their therapeutic effects on EAE. In sum, our study highlights a great clinical potential of IFN-γ-hUCMSCs for multiple sclerosis (MS) treatment.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (81870848); Rong Xiang Regenerative Medicine Foundation; and Youth Talent Fund of the Second Hospital of Shandong University (2018YT37).

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Authors and Affiliations

  1. Department of Neurology Medicine, The Second Hospital of Shandong University, 247th of Beiyuan Rd., Jinan, Shandong, China

    Xiaoyan Zhou, Li Liu, Zhaohong Xie, Xiangtian Liu, Yingying Xu, Fan Li & Jianzhong Bi

  2. Department of Hematology, Institute of Biotherapy for Hematological Malignancies, The Second Hospital of Shandong University, 247th of Beiyuan Rd., Jinan, Shandong, China

    Xiaoli Liu & Chengyun Zheng

  3. Shandong University-Karolinska Institute Collaboration Laboratory for Stem Cell Research, Jinan, Shandong, China

    Xiaoli Liu & Chengyun Zheng

  4. Department of Neurosurgery, The Second Hospital of Shandong University, Jinan, Shandong, China

    Chao Han

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  1. Xiaoyan Zhou
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Zhou, X., Liu, X., Liu, L. et al. Transplantation of IFN-γ Primed hUCMSCs Significantly Improved Outcomes of Experimental Autoimmune Encephalomyelitis in a Mouse Model. Neurochem Res 45, 1510–1517 (2020). https://doi.org/10.1007/s11064-020-03009-y

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