title: Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA), a motor neuron disease (MND) and one of the most common genetic causes of infant mortality, currently has no cure. Patients with SMA exhibit muscle weakness and hypotonia. Stem cell transplantation is a potential therapeutic strategy for SMA and other MNDs. In this study, we isolated spinal cord neural stem cells (NSCs) from mice expressing green fluorescent protein only in motor neurons and assessed their therapeutic effects on the phenotype of SMA mice. Intrathecally grafted NSCs migrated into the parenchyma and generated a small proportion of motor neurons. Treated SMA mice exhibited improved neuromuscular function, increased life span, and improved motor unit pathology. Global gene expression analysis of laser-capture-microdissected motor neurons from treated mice showed that the major effect of NSC transplantation was modification of the SMA phenotype toward the wild-type pattern, including changes in RNA metabolism proteins, cell cycle proteins, and actin-binding proteins. NSC transplantation positively affected the SMA disease phenotype, indicating that transplantation of NSCs may be a possible treatment for SMA.
authors.affiliation: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan and IRCCS Foundation Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.forename: Martina
authors.initials: M
authors.lastname: Nardini
authors.forename: Chiara
authors.initials: C
authors.lastname: Donadoni
authors.forename: Sabrina
authors.initials: S
authors.lastname: Salani
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Saladino
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Fortunato
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.forename: Federica
authors.initials: F
authors.lastname: Locatelli
authors.forename: Giorgia
authors.initials: G
authors.lastname: Menozzi
authors.forename: Sandra
authors.initials: S
authors.lastname: Strazzer
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi