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Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice
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Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice
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Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice
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Journal Article
Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice
2009
Overview
Amyotrophic lateral sclerosis (ALS) is the most common adult onset motoneuron disease. The etiology and precise pathogenic mechanisms of the disease remain unknown, and there is no effective treatment. Vascular endothelial growth factor (VEGF) has recently been shown to exert direct neurotrophic and neuroprotective effects in animal models of ALS. Here we show that intrathecal transplantation of immortalized human neural stem cells (NSCs) overexpressing human VEGF gene (HB1.F3.VEGF) significantly delayed disease onset and prolonged the survival of the SOD1G93A mouse model of ALS. At 4 weeks, post-transplantation grafted cells were found within the gray matter of the spinal cord. Furthermore, transplanted F3.VEGF cells that express neuronal phenotype (MAP2+) were found in the anterior horn of the spinal cord gray matter indicating that the transplanted human NSCs migrated into the gray matter, took the correct structural position, integrated into the spinal cord anterior horn and differentiated into motoneurons. Intrathecal transplantation of F3.VEGF cells provides a neuroprotective effect in the diseased spinal cord by concomitant downregulation of proapoptotic proteins and upregulation of antiapoptotic proteins. Our results suggest that this treatment modality of intrathecal transplantation of human NSCs genetically modified to overexpress neurotrophic factor(s) might be of value in the treatment of ALS patients without significant adverse effects.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Amyotrophic Lateral Sclerosis - physiopathology
/ Amyotrophic Lateral Sclerosis - therapy
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Animals
/ Applied cell therapy and gene therapy
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Etiology
/ Fundamental and applied biological sciences. Psychology
/ Health. Pharmaceutical industry
/ Humans
/ Industrial applications and implications. Economical aspects
/ Mice
/ Rodents
/ Stem Cell Transplantation - methods
/ Transfusions. Complications. Transfusion reactions. Cell and gene therapy
/ Vascular endothelial growth factor
