title: Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis.
abstract: Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Center, Multiple Sclerosis Research Center, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Coleman
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Center, Multiple Sclerosis Research Center, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Ronika
authors.initials: R
authors.lastname: Leang
authors.affiliation: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Ha
authors.initials: H
authors.lastname: Tran
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Center, Multiple Sclerosis Research Center, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kopf
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Center, Multiple Sclerosis Research Center, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Walsh
authors.affiliation: Reeve-Irvine Research Center, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Ilse
authors.initials: I
authors.lastname: Sears-Kraxberger
authors.affiliation: Reeve-Irvine Research Center, Departments of Anatomy & Neurobiology, Neurobiology & Behavior, and Neurosurgery, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Oswald
authors.initials: O
authors.lastname: Steward
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
authors.affiliation: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: Loring
authors.affiliation: Department of Molecular Biology and Biochemistry, Sue and Bill Gross Stem Cell Center, Multiple Sclerosis Research Center, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lane
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000628:therapy*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2