Human ESC-Derived MSCs Outperform Bone Marrow MSCs in the Treatment of an EAE Model of Multiple Sclerosis

Summary Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stem cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs) may be better suited for clinical treatment of MS because of their unlimited and stable supply. Here, we show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse experimental autoimmune encephalitis (EAE) model of MS, and that the EAE disease-modifying effect of hES-MSCs is significantly greater than that of human bone-marrow-derived MSCs (BM-MSCs). Our evidence also suggests that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE therapeutic activity of these cells. A distinct ability to extravasate and migrate into inflamed CNS tissues may also be associated with the robust therapeutic effects of hES-MSCs on EAE.
Highlights • hES-MSCs show increased anti-EAE effects relative to adult human BM-MSCs • hES-MSCs express fewer proinflammatory cytokines than BM-MSCs • hES-MSCs enter the CNS more efficiently than BM-MSCs in EAE
Mesenchymal stem cells (MSCs) offer a potential therapy for multiple sclerosis. Xu, Lanza, and colleagues show that MSCs derived from human embryonic stem cells (hES-MSCs) significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse EAE model of multiple sclerosis, and that the disease-inhibitory effect of hES-MSCs is remarkably greater than that of human bone-marrow-derived MSCs.