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Human motor neurons generated from neural stem cells delay clinical onset and prolong life in ALS mouse model.

Authors
  • Lee, Hong J1
  • Kim, Kwang S2
  • Ahn, Jin1
  • Bae, Hye M3
  • Lim, Inja3
  • Kim, Seung U4
  • 1 Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea. , (North Korea)
  • 2 Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea; Department of Physiology, Chung-Ang University College of Medicine, Seoul, Korea. , (North Korea)
  • 3 Department of Physiology, Chung-Ang University College of Medicine, Seoul, Korea. , (North Korea)
  • 4 Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea; Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, British Columbia, Canada. , (Canada)
Type
Published Article
Journal
PLoS ONE
Publisher
Public Library of Science
Publication Date
Jan 01, 2014
Volume
9
Issue
5
Identifiers
DOI: 10.1371/journal.pone.0097518
PMID: 24844281
Source
Medline
License
Unknown

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neuron disease. The etiology and pathogenic mechanisms of the disease remain unknown, and there is no effective treatment. Here we show that intrathecal transplantation of human motor neurons derived from neural stem cells (NSCs) in spinal cord of the SOD1G93A mouse ALS model delayed disease onset and extended life span of the animals. When HB1.F3.Olig2 (F3.Olig2) cells, stable immortalized human NSCs encoding the human Olig2 gene, were treated with sonic hedgehog (Shh) protein for 5-7 days, the cells expressed motor neuron cell type-specific phenotypes Hb9, Isl-1 and choline acetyltransferase (ChAT). These F3.Olig2-Shh human motor neurons were transplanted intrathecally in L5-L6 spinal cord of SOD1G93A mice, and at 4 weeks post-transplantation, transplanted F3.Olig2-Shh motor neurons expressing the neuronal phenotype markers NF, MAP2, Hb9, and ChAT were found in the ventral horn of the spinal cord. Onset of clinical signs in ALS mice with F3.Olig2-Shh motor neuron implants was delayed for 7 days and life span of animals was significantly extended by 20 days. Our results indicate that this treatment modality of intrathecal transplantation of human motor neurons derived from NSCs might be of value in the treatment of ALS patients without significant adverse effects.

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