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Combined Treatment with Methylprednisolone and Human Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Experimental Autoimmune Encephalomyelitis

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although advances have been made in the treatment of MS, such as the use of IFN-β, glucocorticoids and stem cells, the therapeutic effects of these treatments are not sufficient. In the present study, we evaluated whether the combination of methylprednisolone (MP) and human bone marrow-derived mesenchymal stem cells (BM-MSCs) could enhance the therapeutic effectiveness in experimental autoimmune encephalomyelitis (EAE), a model for MS. EAE was induced by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55). The immunized mice received an intraperitoneal injection of MP (20 mg/kg), an intravenous injection of BM-MSCs (1 × 106 cells) or both on day 14 after immunization. Combination treatment significantly ameliorated the clinical symptoms, along with attenuating inflammatory infiltration and demyelination, compared to either treatment alone. Secretion of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17) was significantly reduced, and anti-inflammatory cytokines (IL-4, IL-10) was significantly increased by the combination treatment as compared to either treatment alone. Flow cytometry analysis of MOG-reactivated T cells in spleen showed that combination treatment reduced the number of CD4+CD45+ and CD8+ T cells, and increased the number of CD4+CD25+Foxp3+ regulatory T cells. Furthermore, combination treatment enhanced apoptosis in MOG-reactivated CD4+ T cells, a key cellular subset in MS pathogenesis. Combination treatment with MP and BM-MSCs provides a novel treatment protocol for enhancing therapeutic effects in MS.

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Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2054772, 2016R1D1A1B03931146) and by the Ministry of Science, ICT and Future Planning (2014R1A2A2A01004525).

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Authors and Affiliations

  1. Department of Biomedicine and Health Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Korea

    Mi Jin Kim & Sin-Soo Jeun

  2. Department of Clinical Laboratory Science, Daejeon Health Institute of Technology, 21 Chungjeongno, Dong-gu, Daejeon, 34504, Korea

    Chung Heon Ryu & Won Shik Kim

  3. Department of Neurosurgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Korea

    Seong Muk Kim, Jung Yeon Lim & Sin-Soo Jeun

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  1. Mi Jin Kim
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Correspondence to Chung Heon Ryu or Sin-Soo Jeun.

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All animal experiments in this study were approved by the Institutional Animal Care and Use Committee (IACUC), the Catholic University of Korea (Permit Number; 2015-0147-01).

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Kim, M.J., Ryu, C.H., Kim, S.M. et al. Combined Treatment with Methylprednisolone and Human Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Experimental Autoimmune Encephalomyelitis. Tissue Eng Regen Med 15, 183–194 (2018). https://doi.org/10.1007/s13770-017-0101-y

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