Objective: Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). The current treatments available for MS patients are predominantly non-specific immunomodulators, which are only effective in 30% of relapsing-remitting (RR) patients, have no long-term beneficial effects and are often associated with significant side effects. In recent years it has been found that stem cells, such as mesenchymal stromal cells (MSC), and more recently human amnion epithelial cells (hAEC), have the ability to suppress immune responses in vitro and in vivo and can differentiate into many cell lineages in vitro. These properties make them very attractive candidates for MS in that they may dampen CNS inflammation, reduce damage and may have neuroregenerative potential. Accordingly, we have investigated the potential immunoregulatory effects of hAECs as a possible therapy for an MS-like disease, EAE (experimental autoimmune encephalomyelitis) in mice.
Results: We found that in vitro hAECs can suppress both specific and non-specific T-cell proliferation and decrease the amount of pro-inflammatory cytokines produced by T-cells. We also found that hAECs inhibited the upregulation of CD25 (an activation marker) on stimulated T-cells and T-cells retained their naïve phenotype in the presence of hAECs. In vivo studies have also revealed that hAECs not only suppress the development of RR-EAE but also prevent relapse in these mice. Mice protected from EAE by hAEC administration had reduced MOG-specific T-cell responses and produced less pro-inflammatory cytokines upon antigen specific and non-specific stimulation. Further investigations also revealed that hAEC treated mice had increased percentages of Th2 cells in the peripheral lymphoid organs and, most importantly, within the CNS.
Conclusion: These results imply that hAECs produce their immuno-egulatory effect in part by initiating an anti-inflammatory response directly within the CNS and by suppressing the activation of T-cells. Collectively this work suggests that hAECs hold promise for the treatment of autoimmune diseases, like MS.