Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy

Stefania Corti, Monica Nizzardo, Martina Nardini, Chiara Donadoni, Sabrina Salani, Dario Ronchi, Francesca Saladino, Andreina Bordoni, Francesco Fortunato, Roberto Del Bo, Dimitra Papadimitriou, Federica Locatelli, Giorgia Menozzi, Sandra Strazzer, Nereo Bresolin, Giacomo P. Comi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3316-3330
Number of pages15
JournalJournal of Clinical Investigation
Volume118
Issue number10
DOIs
Publication statusPublished - Oct 1 2008

ASJC Scopus subject areas

  • Medicine(all)

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