Evaluating the Therapeutic Potential of Transplantation of Neural Precursor Cells for Treating the Autoimmune Disease Multiple Sclerosis

Abstract

Abstract Multiple Sclerosis is a chronic, autoimmune disease for which there is currently no cure. Previous studies suggest transplantation of neural precursor cells (NPCs) is a promising therapeutic strategy to treat neurological disorders. Using two mouse models of MS, experimental autoimmune encephalomyelitis (EAE) and murine hepatitis virus (MHV), we have observed remyelination and decreased neuroinflammation when mice received an intra-spinal transplant of syngeneic mouse GFP-NPCs. This recovery was due to replacement of damaged cells and had little effect upon immune responses. In contrast, transplantation of xenogeneic human embryonic stem cell (hESC) derived NPCs (hNPCs) or induced pluripotent stem cell (iPSC) derived NPCs (hiNPCs) modulates the host immune response. Mice receiving intra-spinal transplants of human NPCs displayed less demyelination, decreased neuroinflammation, and an increase in T regulatory cells (Tregs). Recovery was not a result of cell replacement by hNPCs because transplanted cells underwent rapid xenograft rejection. Importantly, ablation of Tregs abrogated clinical and histopathological improvement mediated by hNPC transplantation. Furthermore, hNPCs promote the induction of naïve T cells into Tregs in co-cultures in vitro. However, the mechanisms and factors that propagate Treg induction and function resulting in subsequent endogenous remyelination remain undiscovered. We hypothesize rejection of NPCs plays a role in generation of Tregs in vitro and in vivo. Future experiments will focus on elucidating the factors from hNPCs that are responsible for Treg differentiation and evaluate the ability of syngeneic, allogeneic, and xenogeneic NPCs to generate Tregs.