Human neural stem cell-derived cholinergic neurons innervate muscle in motoneuron deficient adult rats

Junling Gao, R. E. Coggeshall, Y. I. Tarasenko, Ping Wu

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Motoneuron damage occurs in spinal cord injury and amyotrophic lateral sclerosis. Current advances offer hope that human embryonic stem cells [Science 282 (1998) 1145] or neural stem cells (NSC) [Exp Neurol 161 (2000) 67; Exp Neurol 158 (1999) 265; J Neurosci Methods 85 (1998) 141; Proc Natl Acad Sci USA 97 (2000) 14720; Exp Neurol 156 (1999) 156] may be donors to replace lost motoneurons. Previously, we developed a priming procedure that produced cholinergic cells that resemble motoneurons from human NSCs grafted into adult rat spinal cord [Nat Neurosci 5 (2002a) 1271]. However, effective replacement therapy will ultimately rely on successful connection of new motoneurons with their muscle targets. In this study, we examined the potential of human fetal NSC transplantation to replace lost motoneurons in an animal model of chronic motoneuron deficiency (newborn sciatic axotomy) [J Comp Neurol 224 (1984) 252; J Neurobiol 23 (1992) 1231]. We found, for the first time, that human neural stem cell-derived motoneurons send axons that pass through ventral root and sciatic nerve to form neuromuscular junctions with their peripheral muscle targets. Furthermore, this new cholinergic innervation correlates with partial improvement of motor function.

Original languageEnglish (US)
Pages (from-to)257-262
Number of pages6
JournalNeuroscience
Volume131
Issue number2
DOIs
StatePublished - 2005

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Cholinergic Neurons
Neural Stem Cells
Motor Neurons
Muscles
Cholinergic Agents
Fetal Stem Cells
Axotomy
Spinal Nerve Roots
Neuromuscular Junction
Amyotrophic Lateral Sclerosis
Stem Cell Transplantation
Sciatic Nerve
Spinal Cord Injuries
Axons
Spinal Cord
Animal Models

Keywords

  • Axotomy
  • Cell therapy
  • Motoneuron disease
  • Neuromuscular junction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Human neural stem cell-derived cholinergic neurons innervate muscle in motoneuron deficient adult rats. / Gao, Junling; Coggeshall, R. E.; Tarasenko, Y. I.; Wu, Ping.

In: Neuroscience, Vol. 131, No. 2, 2005, p. 257-262.

Research output: Contribution to journalArticle

Gao, Junling ; Coggeshall, R. E. ; Tarasenko, Y. I. ; Wu, Ping. / Human neural stem cell-derived cholinergic neurons innervate muscle in motoneuron deficient adult rats. In: Neuroscience. 2005 ; Vol. 131, No. 2. pp. 257-262.
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