Combined Treatment with Methylprednisolone and Human Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Experimental Autoimmune Encephalomyelitis.
10.1007/s13770-017-0101-y
- Author:
Mi Jin KIM
1
;
Chung Heon RYU
;
Seong Muk KIM
;
Jung Yeon LIM
;
Won Shik KIM
;
Sin Soo JEUN
Author Information
1. Department of Biomedicine and Health Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. ssjeun@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Methylprednisolone;
Bone marrow mesenchymal stem cells;
Experimental autoimmune encephalomyelitis
- MeSH:
Animals;
Apoptosis;
Central Nervous System;
Clinical Protocols;
Cytokines;
Demyelinating Diseases;
Encephalomyelitis, Autoimmune, Experimental*;
Flow Cytometry;
Glucocorticoids;
Humans*;
Immunization;
Injections, Intraperitoneal;
Injections, Intravenous;
Mesenchymal Stromal Cells*;
Methylprednisolone*;
Mice;
Multiple Sclerosis;
Myelin-Oligodendrocyte Glycoprotein;
Spleen;
Stem Cells;
T-Lymphocytes;
T-Lymphocytes, Regulatory;
Therapeutic Uses
- From:
Tissue Engineering and Regenerative Medicine
2018;15(2):183-194
- CountryRepublic of Korea
- Language:English
-
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.
