Emergence of T Regulatory Cells and Repair Following Neural Precursor Cell Transplantation in Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis Laura L. McIntyre1, Thomas E. Lane2, Craig M. Walsh1 1Department of Molecular Biology & Biochemistry, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA; 2Division of Microbiology & Immunology, Department of Pathology, University of Utah, School of Medicine, Salt Lake City, UT Multiple Sclerosis (MS) is a chronic, inflammatory, autoimmune disease that affects the central nervous system for which there is no cure. Defects in neurological function are a result of demyelination and axonal loss caused by infiltrating lymphocytes. Transplantation of neural precursor cells (NPCs) is a promising therapeutic strategy to treat neurological diseases. NPCs have been shown to reduce neuroinflammation and promote remyelination in animal models of human neurological disorders, such as Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and spinal cord injury. However, studies evaluating NPC transplantation often utilize a syngeneic donor or immune suppressed subjects. Therefore, it is imperative to consider the immune response transplanted cells may elicit. We report that human neural precursor cells (hNPCs) promote T regulatory cells (Tregs) which influence endogenous repair pathways to promote remyelination in a murine model of MS. Using a murine model of MS, Experimental Autoimmune Encephalomyelitis, we observed a decrease in demyelination and decreased neuroinflammation in mice receiving an intra-spinal transplant of syngeneic mouse NPCs, which replaced damaged cells. Alternatively, mice receiving transplants of xenogeneic human NPCs displayed a decrease in neuroinflammation, remyelination, and an increase in CD4+CD25+FoxP3+ Tregs. Recovery was not a result of direct cell replacement as hNPCs underwent xenograft rejection. Importantly, ablation of Tregs abrogated histopathological improvement mediated by hNPC transplantation. Furthermore, hNPCs promote Tregs in vitro in a contact dependent manner. These findings support an emerging role for Tregs in promoting tissue regeneration, distinct from immune modulation.
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