Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

Lu Chen; Ronald Coleman; Ronika Leang; Ha Tran; Alexandra Kopf; Craig M. Walsh; Ilse Sears-Kraxberger; Oswald Steward; Wendy B. Macklin; Jeanne F. Loring; Thomas E. Lane

doi:10.1016/j.stemcr.2014.04.005

Stem Cell Reports (Jun 2014)

Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

Lu Chen,
Ronald Coleman,
Ronika Leang,
Ha Tran,
Alexandra Kopf,
Craig M. Walsh,
Ilse Sears-Kraxberger,
Oswald Steward,
Wendy B. Macklin,
Jeanne F. Loring,
Thomas E. Lane

Affiliations

Lu Chen: 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
Ronald Coleman: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Ronika Leang: 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
Ha Tran: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Alexandra Kopf: 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
Craig M. Walsh: 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
Ilse Sears-Kraxberger: Reeve-Irvine Research Center, University of California, Irvine, Irvine, CA 92697, USA
Oswald Steward: Reeve-Irvine Research Center, Departments of Anatomy & Neurobiology, Neurobiology & Behavior, and Neurosurgery, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA
Wendy B. Macklin: Department of Cell and Developmental Biology, School of Medicine, University of Colorado, Aurora, CO 80045, USA
Jeanne F. Loring: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Thomas E. Lane: 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

DOI: https://doi.org/10.1016/j.stemcr.2014.04.005
Journal volume & issue: Vol. 2, no. 6
pp. 825 – 837

Abstract

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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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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