Dual transplantation of human neural stem cells into cervical and lumbar cord ameliorates motor neuron disease in SOD1 transgenic rats
Highlights
► Human NSCs were grafted into cervical and lumbar spinal segments of SOD1 G93A rats. ► Grafted human NSCs survived and differentiated in both cervical and lumbar segments. ► Dual-segment grafts delayed disease onset and prolonged life span of SOD1 G93A rats. ► Dual-segment grafts attenuated motor weakness in SOD1 G93A rats.
Section snippets
Acknowledgments
This work was supported by NIH grant RO1 NS045140-03, the Muscular Dystrophy Association, and the Robert Packard Center for ALS Research at Johns Hopkins.
References (36)
- et al.
ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions
Neuron
(1997) - et al.
Local GDNF expression mediated by lentiviral vector protects facial nerve motoneurons but not spinal motoneurons in SOD1(G93A) transgenic mice
Neurobiol. Dis.
(2004) - et al.
Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis
Neurobiol. Dis.
(2002) - et al.
Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model of ALS
Neurobiol. Dis.
(2006) Interaction between amino acid neurotransmitters and opioid receptors in hyperthermia-induced brain pathology
Prog. Brain Res.
(2007)- et al.
Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis
Neurobiol. Dis.
(2008) - et al.
Activation of programmed cell death markers in ventral horn motor neurons during early presymptomatic stages of amyotrophic lateral sclerosis in a transgenic mouse model
Brain Res.
(2004) - et al.
An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
Neuron
(1995) - et al.
Neuregulin-1 enhances depolarization-induced GABA release
Neuron
(2007) - et al.
Increased survival and function of SOD1 mice after glial cell-derived neurotrophic factor gene therapy
Hum. Gene Ther.
(2002)
Development of a rat model of amyotrophic lateral sclerosis expressing a human SOD1 transgene
Neuropathology
A sensitive and reliable locomotor rating scale for open field testing in rats
J. Neurotrauma
Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis
Ann. Neurol.
Current status of SOD1 mutations in familial amyotrophic lateral sclerosis
Amyotroph. Lateral Scler. Other Motor Neuron Disord.
Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation
Science
Natural history of amyotrophic lateral sclerosis in a database population. Validation of a scoring system and a model for survival prediction
Brain
Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)
Proc. Natl. Acad. Sci. U.S.A.
Single factors direct the differentiation of stem cells from the fetal and adult central nervous system
Genes Dev.
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