Tissue Eng Regen Med.  2018 Apr;15(2):183-194. 10.1007/s13770-017-0101-y.

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

• Kim MJ
• Ryu CH
• Kim SM
• Lim JY
• Kim WS
• Jeun SS

• KMID: 2410513
• DOI: http://doi.org/10.1007/s13770-017-0101-y

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.

Keyword

Methylprednisolone; Bone marrow mesenchymal stem cells; Experimental autoimmune encephalomyelitis

MeSH Terms

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
Cytokines
Glucocorticoids
Methylprednisolone
Myelin-Oligodendrocyte Glycoprotein
Therapeutic Uses