Neural stem cells LewisX + CXCR4 + modify disease progression in an amyotrophic lateral sclerosis model

Stefania Corti, Federica Locatelli, Dimitra Papadimitriou, Roberto Del Bo, Monica Nizzardo, Martina Nardini, Chiara Donadoni, Sabrina Salani, Francesco Fortunato, Sandra Strazzer, Nereo Bresolin, Giacomo P. Comi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1289-1305
Number of pages17
JournalBrain
Volume130
Issue number5
DOIs
Publication statusPublished - May 2007

Keywords

  • Amyotrophic lateral sclerosis
  • Motor neuron
  • Neural stem cell
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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