Studio di sottopopolazioni cellulari staminali neuronali nello sviluppo di una terapia cellulomediata per le malattie del motoneurone

Neural stem cell subpopulations for cell-mediated therapy of motor neuron diseases Stem cell transplantation is a potential therapeutic strategy for motor neurons disease such as Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA) not only via cell replacement, but also by modification of the extracellular motor neuronal environment, through a trophic and neuroprotective effect, as well as immunomodulation strategies. We investigated the potential of a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase (ALDH) activity or double positive for Lewis X and the chemokine receptor CXCR4 (LeX+CXCR4+) to modify disease progression of nmd mice, an animal model of SMARD1 and SOD1-G93A mice, and animal model of ALS. In vitro, after exposure to morphogenetic stimuli these cells generate cholinergic motor neuron-like cells upon differentiation. ALDH(hi)SSC(lo) and LeX+CXCR4+ stem cells when transplanted in nmd and SOD1G93A mice generate motor neurons properly localized in the spinal cord ventral horns. Transplanted animals presented delayed disease progression, sparing of motor neurons and ventral root axons and increased lifespan. Our results support the therapeutic potential of Neural Stem Cell fractions through both neurogenesis and growth factors release in motor neuron disorders.