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

Abstract

BackgroundMultiple 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.MethodsUsing 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.ResultsIn 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.ConclusionThe 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.

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…In a subsequent study (McDonald et al 2015), the same authors extended previous findings in a relapsing-remitting model of EAE in NOD/Lt mice. They demonstrated that the transplantation of allogenic hAECs at the disease onset significantly ameliorates the degree of disease by inhibiting Th17 and Th1 cells production within the peripheral lymphoid organs and CNS.…”

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

“…Interestingly, the protective effects in the setting of experimental spinal cord injury was profound with hAEC than MSC from umbilical cord. hAEC transplantation also modulated activation of astrocytes and microglia in this model of spinal cord injury .…”

“…In a rat model of PD with 6‐hydroxydopamine lesions, a higher survival rate of dopaminergic neurons was reported, along with an increase in dopaminergic neurons in the substantia nigra and restrained stem cells growth . Transplantation of hAEC into a rat model of spinal cord injury significantly reduced mechanical allodynia , suggesting that hAEC transplantation may be therapeutic for spinal cord injury related neuropathic pain. Interestingly, the protective effects in the setting of experimental spinal cord injury was profound with hAEC than MSC from umbilical cord.…”

Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence

“…Its clinical success was ascribed not only to the enhanced wound-healing properties, but also to the lower inflammatory response that cells or amniotic membranes offered when compared to other available sources. As the signaling mechanisms involved in the innate immunomodulatory activity and anti-inflammatory properties of AECs have been largely elucidated, there is a momentum toward the use of AECs in the resolution of inflammatory diseases [57, 58, 59, 60]. …”