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, 468 (3), 190-4

Dose-dependent Efficacy of ALS-human Mesenchymal Stem Cells Transplantation Into Cisterna Magna in SOD1-G93A ALS Mice

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Dose-dependent Efficacy of ALS-human Mesenchymal Stem Cells Transplantation Into Cisterna Magna in SOD1-G93A ALS Mice

Heejaung Kim et al. Neurosci Lett.

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Although the underlying cause of the disease remains unclear, a variety of pathogenic mechanisms have been proposed. Despite promising preclinical studies showing the modification of the disease progression, most trials have failed to demonstrate any significant improvement in outcome. Stem cell therapy therefore has been proposed as an alternative therapy for ALS. In this study, we evaluated the dose-dependent effects of human bone marrow mesenchymal stem cells (hMSCs) obtained from an ALS patient (ALS-hMSCs) on SOD1 mice via intrathecal injection and showed its practicality for hMSCs. We transplanted different doses (1x10(4), 2x10(5), and 1x10(6)) of ALS-hMSCs into the cisterna magna and performed clinical observations including symptom onset, survival time, and locomotor performance using the rotarod test. Nissl staining was performed to evaluate motor neurons in lumbar spinal cord sections at 109 days, and transplanted cells were evaluated by immuno-fluorescence staining at the end stage. A cell dose of 1x10(6) cells significantly prolonged life span and delayed the decline of motor performance. At this dose, the average number of motor neurons was significantly higher than those of the untreated and 1x10(4) cell treated groups. Most injected hMSCs distributed in the ventricular system and subarachnoid space, while some migrated into the brain and spinal cord. These data suggest that intrathecal injection with an optimized cell number could be a potential route for stem cell therapy in ALS patients.

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