Adult olfactory bulb neural precursor cell grafts provide temporary protection from motor neuron degeneration, improve motor function, and extend survival in amyotrophic lateral sclerosis mice

Lee J Martin, Zhiping Liu

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis is a fatal disease caused by degeneration of motor neurons (MNs). We transplanted multipotent neural precursor cell (NPC)-neurospheres from mouse olfactory bulb (OB) into the spinal cord of transgenic mice that develop MN degeneration because of human mutant superoxide dismutase-1 (mSOD1). Adult NPCs were isolated from the OB core of transgenic mice expressing green fluorescent protein, human wild-type SOD1, or human mSOD1. mSOD1 mice received lumbar spinal cord transplants of OB-NPC neurospheres at preclinical stages of disease (70 days old). Control mSOD1 mice received dead cells or recombinant green fluorescent protein. OB-NPCs attenuated the loss of motor function and wasting. They delayed disease onset to ∼117 days, compared with control onset at ∼90 days. The lifespan of NPC recipient mice was extended (∼170 days) compared with the lifespan of controls (∼140 days). Transplanted OB-NPCs differentiated into large spinal neurons positive for choline acetyltransferase, interneurons, and glial cells. Loss of endogenous MNs was attenuated in mSOD1 mice with transplants. New neurons formed myelinated axons and synapses. NPC-derived neurons issued axons that grew into peripheral nerve. OB-NPCs also differentiated into oligodendrocytes and astrocytes that contacted neuronal processes. We conclude that transplantation of adult OB-NPCs is therapeutic for mouse amyotrophic lateral sclerosis.

Original languageEnglish (US)
Pages (from-to)1002-1018
Number of pages17
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number11
DOIs
StatePublished - Nov 2007

Fingerprint

Nerve Degeneration
Olfactory Bulb
Amyotrophic Lateral Sclerosis
Motor Neurons
Transplants
Survival
Spinal Cord
Green Fluorescent Proteins
Neurons
Transgenic Mice
Axons
Choline O-Acetyltransferase
Oligodendroglia
Interneurons
Peripheral Nerves
Recombinant Proteins
Neuroglia
Astrocytes
Synapses
Transplantation

Keywords

  • Adult stem cell
  • Motor neuron disease
  • Motor neuron replacement
  • Mutant superoxide dismutase-1 (SOD1)
  • Spinal cord injury
  • Stem cell therapy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

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abstract = "Amyotrophic lateral sclerosis is a fatal disease caused by degeneration of motor neurons (MNs). We transplanted multipotent neural precursor cell (NPC)-neurospheres from mouse olfactory bulb (OB) into the spinal cord of transgenic mice that develop MN degeneration because of human mutant superoxide dismutase-1 (mSOD1). Adult NPCs were isolated from the OB core of transgenic mice expressing green fluorescent protein, human wild-type SOD1, or human mSOD1. mSOD1 mice received lumbar spinal cord transplants of OB-NPC neurospheres at preclinical stages of disease (70 days old). Control mSOD1 mice received dead cells or recombinant green fluorescent protein. OB-NPCs attenuated the loss of motor function and wasting. They delayed disease onset to ∼117 days, compared with control onset at ∼90 days. The lifespan of NPC recipient mice was extended (∼170 days) compared with the lifespan of controls (∼140 days). Transplanted OB-NPCs differentiated into large spinal neurons positive for choline acetyltransferase, interneurons, and glial cells. Loss of endogenous MNs was attenuated in mSOD1 mice with transplants. New neurons formed myelinated axons and synapses. NPC-derived neurons issued axons that grew into peripheral nerve. OB-NPCs also differentiated into oligodendrocytes and astrocytes that contacted neuronal processes. We conclude that transplantation of adult OB-NPCs is therapeutic for mouse amyotrophic lateral sclerosis.",
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