Abstract
ALS is a devastating disease resulting in degeneration of motor neurons (MNs) in the brain and spinal cord. The survival of MNs strongly depends on surrounding glial cells and neurotrophic support from muscles. We previously demonstrated that boundary cap neural crest stem cells (bNCSCs) can give rise to neurons and glial cells in vitro and in vivo and have multiple beneficial effects on co-cultured and co-implanted cells, including neural cells. In this paper, we investigate if bNCSCs may improve survival of MNs harboring a mutant form of human SOD1 (SOD1G93A) in vitro under normal conditions and oxidative stress and in vivo after implantation to the spinal cord. We found that survival of SOD1G93A MNs in vitro was increased in the presence of bNCSCs under normal conditions as well as under oxidative stress. In addition, when SOD1G93A MN precursors were implanted to the spinal cord of adult mice, their survival was increased when they were co-implanted with bNCSCs. These findings show that bNCSCs support survival of SOD1G93A MNs in normal conditions and under oxidative stress in vitro and improve their survival in vivo, suggesting that bNCSCs have a potential for the development of novel stem cell-based therapeutic approaches in ALS models.
Highlights
Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder affecting primarily upper and lower motor neurons (MNs), and usually leading to the death of the patient, most commonly due to respiratory failure
We show that boundary cap neural crest stem cells (bNCSCs) exert a significant survival promoting effect on SOD1G93A MN in vitro as well as after co-implantation to the spinal cord
For this reason we have tested if bNCSCs are susceptible to oxidative stress and found that they are resistant to exposure to hydrogen peroxide in concentrations which significantly impair survival of SOD1G93A MNs
Summary
Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder affecting primarily upper and lower motor neurons (MNs), and usually leading to the death of the patient, most commonly due to respiratory failure. Riluzole acts by attenuating excitotoxic impact on endangered MNs, and is currently the only available approved ALS treatment, but offers not more than a few months extended life expectancy [1]. About 10% of ALS cases are familial and several genetic mutations linked to this group of patients have been identified. Mutations in superoxide dismutase (SOD) are found in about 20% of familial cases and in a few percent of sporadic ALS cases [3]. More than 150 SOD1 mutations have been identified and SOD1G93A is the most widely studied model for ALS pathogenesis [3]
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