title: Neural stem cells LewisX+ CXCR4+ modify disease progression in an amyotrophic lateral sclerosis model.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of the motor neurons. We tested whether treatment of superoxide dismutase (SOD1)-G93A transgenic mouse, a model of ALS, with a neural stem cell subpopulation double positive for Lewis X and the chemokine receptor CXCR4 (LeX+CXCR4+) can modify the disease's progression. In vitro, after exposure to morphogenetic stimuli, LeX+CXCR4+ cells generate cholinergic motor neuron-like cells upon differentiation. LeX+CXCR4+ cells deriving from mice expressing Green Fluorescent Protein in all tissues or only in motor neurons, after a period of priming in vitro, were grafted into spinal cord of SOD1-G93A mice. Transplanted transgenic mice exhibited a delayed disease onset and progression, and survived significantly longer than non-treated animals by 23 days. Examination of the spinal cord revealed integration of donor-derived cells that differentiated mostly in neurons and in a lower proportion in motor neuron-like cells. Quantification of motor neurons of the spinal cord suggests a significant neuroprotection by LeX+CXCR4+ cells. Both VEGF- and IGF1-dependent pathways were significantly modulated in transplanted animals compared to controls, suggesting a role of these neurotrophins in MN protection. Our results support the therapeutic potential of neural stem cell fractions through both neurogenesis and growth factors release in motor neuron disorders.
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
authors: Stefania
authors: S
authors: Corti
authors: Federica
authors: F
authors: Locatelli
authors: Dimitra
authors: D
authors: Papadimitriou
authors: Roberto
authors: R
authors: Del Bo
authors: Monica
authors: M
authors: Nizzardo
authors: Martina
authors: M
authors: Nardini
authors: Chiara
authors: C
authors: Donadoni
authors: Sabrina
authors: S
authors: Salani
authors: Francesco
authors: F
authors: Fortunato
authors: Sandra
authors: S
authors: Strazzer
authors: Nereo
authors: N
authors: Bresolin
authors: Giacomo P
authors: GP
authors: Comi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000601:surgery*; D000818:Animals; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D002454:Cell Differentiation; D002999:Clone Cells; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D016256:Lewis X Antigen / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009046:Motor Neurons / Q000473:pathology; D039902:Multipotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D009416:Nerve Regeneration; D019718:Receptors, CXCR4 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D016256:Lewis X Antigen; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D013482:Superoxide Dismutase