Int J Stem Cells.  2018 Jun;11(1):68-77. 10.15283/ijsc17052.

Therapeutic Efficacy of Mesenchymal Stem Cells and Mesenchymal Stem Cells-derived Neural Progenitors in Experimental Autoimmune Encephalomyelitis

• Nasri F
• Mohtasebi
• Hashemi E
• Zarrabi M
• Gholijani
• Sarvestani EK

• KMID: 2413502
• DOI: http://doi.org/10.15283/ijsc17052

Abstract

BACKGROUND AND OBJECTIVES
The goal of treatment for MS is to reduce the inflammation and induce the regeneration of degenerated axons. Considering the anti-inflammatory and regenerative capacity of mesenchymal stem cell (MSCs), in this study the therapeutic efficacy of allogeneic MSCs and MSCs-derived neural progenitor cells (MSCs-NPs) was investigated in cellular therapy of chronic experimental autoimmune encephalomyelitis (EAE).
METHODS AND RESULTS
MSCs, MSCs-NPs and MSCs+MSCs-NP were administered intravenously to EAE mice on days 22, 29, and 36 post immunization. The levels of cytokines and PGE2 in sera or supernatant of in vitro cultured splenocytes derived from treated mice were measured by ELISA. The results of this study showed that in comparison to MSCs monotherapy, MSCs-NPs administration had a more profound capability of inhibiting the proliferation of pathogenic MOG35-55-specific T cells, decreasing IFN-γ production and increasing anti-inflammatory IL-10 cytokine production. These findings could be explained by higher ability of in vitro cultured MSCs-NPs in production of PGE2 compared to MSCs. In line with these findings, while the administration of MSCs and MSCs-NPs significantly decreased the clinical scores of EAE in comparison with the untreated EAE group, MSCs-NPs were significantly more efficient in reducing clinical score compared to MSCs. Of interest, combined therapy with MSCs and MSCs-NPs did not provide any benefit over monotherapy with MSCs-NPs.
CONCLUSIONS
In comparison to MSCs, allogenic MSCs-NPs are more potent in the attenuation of EAE.

Keyword

Mesenchymal stem cells; Experimental autoimmune encephalomyelitis; Multiple sclerosis; IFN-γ; PGE2; IL-10

MeSH Terms

Animals
Axons
Cytokines
Dinoprostone
Encephalomyelitis, Autoimmune, Experimental*
Enzyme-Linked Immunosorbent Assay
Immunization
In Vitro Techniques
Inflammation
Interleukin-10
Mesenchymal Stromal Cells*
Mice
Multiple Sclerosis
Regeneration
Stem Cells
T-Lymphocytes
Cytokines
Dinoprostone
Interleukin-10

Figure

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  Fig. 1 MSCs and MSCs-NPs characterization. (A) Mice bone marrow derived MSCs at passage 6 (10× or 20×magnification) and MSCs-NPs at the fourth day post-induction (10×magnification) are compared for their morphology and capability in mesodermal differentiation (osteogenesis and adipogenesis). Neurosphere morphology and reduced ability in osteogenesis and adipogenesis was found in MSCs-NPs (lower row). (B) Cell surface phenotyping of MSCs and MSCs-NPs by flow cytometry. Isotype controls are represented by gray filled histograms.

• 

  Fig. 2 Comparison of MSCs and MSCs-NPs for secretion of PGE2 (A) or IL-10 (B) after 24 hours or 48 hours of culture. Bars represent mean±SD from three experiments. *p<0.05, **p<0.01.

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  Fig. 3 Three times intravenous injection of MSCs, MSCs-NPs and co-injection of MSCs+MSCs-derived NPs significantly decreased EAE clinical scores in treated mice compared to control mice. Error bars represent SEM from day 12 onwards. Arrows indicate times of injection. ***p<0.001.

• 

  Fig. 4 Ex vivo effect of MSCs and MSCs-derived NPs on proliferation of MOG35–55-specific splenocytes in [3H]-Thymidine incorporation. *≤0.05, **≤0.01 and NS: nonsignificant.

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  Fig. 5 Cytokine levels in the supernatant of MOG35–55-stimulated splenocytes. (A, B) IFN-γ and IL-17 levels were significantly decreased in the supernatant of activated splenecytes derived from treated mice compared to control group. (C) IL-10 showed significant increases in the supernatant of activated splenecytes derived from treated animals. Bars represent mean±SD from five mice/condition. *p<0.05, **p<0.02, ***p<0.001.

• 

  Fig. 6 Cytokine levels in the sera of treated and untreated mice. (A) IFN-γ and (B) IL-17 levels were significantly decreased in the sera derived from treated mice while (C) IL-10 levels showed significant increase in sera of treated animals in comparison to untreated ones. Bars represent mean±SD from five mice/condition. *p<0.05, **p=0.015, ***p=0.01.

Reference

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