Introduction: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system affecting more than 2 million people worldwide. Clinically, MS occurs as a relapse-remitting or progressive disease course, and the progressive form currently lacks treatment. The pathophysiology underlying MS is mostly unknown, but inflammatory immune cells and exhaustion of neuronal protective mechanisms play pivotal roles. Advanced medical therapies for progressive MS should therefore include multiple modes of action. Perinatal cells, and Amniotic Epithelial Cells (AEC) in particular, have a plethora of pro-regenerative and anti-inflammatory effects. In women affected by autoimmune disorders, pregnancy reverses such conditions, and the disease flares back once the baby is delivered, underlying the protective role of the placental cells. Human AECs are multipotent stem cells, characterized by active paracrine and trophic effects, supporting angiogenesis, reverse inflammation and fibrosis, but more relevantly, AECs are immunomodulatory cells that modify rather than suppress immune responses.

Methods: We profiled surface molecules (FACS) and secreted mediators (Luminex) in several AEC donors, and measured their effects in vivo. We induced experimental autoimmune encephalitis (EAE) in mice and implanted human AECs once neurological symptoms developed. We measured immune cell phenotypes ex vivo.

Results: Constitutive expression of immunomodulatory molecules (such as HLA-1b, ectonucleotidases) on the surface, as well as paracrine mediators (including HLA-G, IL-2, TWEAK, M-CSF), were confirmed in every batch of AEC we tested. Injection of 0.5 x 106 human AEC resulted in reduced EAE disease scores in mice. In addition, AEC treatment diminished the secretion of pro-inflammatory cytokines from lipopolysaccharide (LPS)-stimulated primary macrophages/microglia and MOG-peptide-stimulated T cells in vitro.

Conclusions: Our data suggest that allogeneic AEC-based cell therapy can effectively reduce the inflammatory burden in the CNS, and may be beneficial for treating a range of neuroinflammatory diseases. Adjunct strategies based on trophic, anti-inflammatory, and immuno-modulatory perinatal stem cells, rather than immune suppression, could improve current cell-based treatments. Human AEC will abet normal immune response towards eventual infective agents and extend cellular therapies to patients commonly not considered due to risks of side effects (e.g. pediatric). Our therapeutic paradigms are applicable MS, and potentially be expanded to a variety of autoimmune disease states.