Immunosuppressive potential of human amnion epithelial cells in the treatment of experimental autoimmune encephalomyelitis

Journal of Neuroinflammation

Claude C.A. Bernard¹  Graham Jenkin⁴  Euan M. Wallace⁴  Rebecca Lim⁴  Christopher Siatskas²  Leon Moussa¹  Guizhi Sun¹  Natalie L. Payne¹  Courtney A. McDonald³ 

[1] Australian Regenerative Medicine Institute, Monash University, Clayton 3800, Australia;Department of Anatomy and Developmental Biology, Monash University, Clayton 3800, VIC, Australia;The Ritchie Centre, MIMR-PHI Institute of Medical Research, Clayton 3800, VIC, Australia;Department of Obstetrics and Gynaecology, Monash University, Clayton 3800, VIC, Australia

关键词: Stem cells;    Demyelination;    Neurodegeneration;    Immunoregulation;    Multiple sclerosis;    Amnion epithelial cells;   

Others  :  1221964
DOI  :  10.1186/s12974-015-0322-8

 received in 2014-12-17, accepted in 2015-05-14,  发布年份 2015

【 摘 要 】

Background

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). In recent years, it has been found that cells such as human amnion epithelial cells (hAECs) have the ability to modulate immune responses in vitro and in vivo and can differentiate into multiple cell lineages. Accordingly, we investigated the immunoregulatory effects of hAECs as a potential therapy in an MS-like disease, EAE (experimental autoimmune encephalomyelitis), in mice.

Methods

Using flow cytometry, the phenotypic profile of hAECs from different donors was assessed. The immunomodulatory properties of hAECs were examined in vitro using antigen-specific and one-way mixed lymphocyte proliferation assays. The therapeutic efficacy of hAECs was examined using a relapsing-remitting model of EAE in NOD/Lt mice. T cell responsiveness, cytokine secretion, T regulatory, and T helper cell phenotype were determined in the peripheral lymphoid organs and CNS of these animals.

Results

In vitro, hAECs suppressed both specific and non-specific T cell proliferation, decreased pro-inflammatory cytokine production, and inhibited the activation of stimulated T cells. Furthermore, T cells retained their naïve phenotype when co-cultured with hAECs. In vivo studies revealed that hAECs not only suppressed the development of EAE but also prevented disease relapse in these mice. T cell responses and production of the pro-inflammatory cytokine interleukin (IL)-17A were reduced in hAEC-treated mice, and this was coupled with a significant increase in the number of peripheral T regulatory cells and naïve CD4+ T cells. Furthermore, increased proportions of Th2 cells in the peripheral lymphoid organs and within the CNS were observed.

Conclusion

The therapeutic effect of hAECs is in part mediated by inducing an anti-inflammatory response within the CNS, demonstrating that hAECs hold promise for the treatment of autoimmune diseases like MS.

【 授权许可】

   
2015 McDonald et al.

【 图 表 】

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