Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA41 neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model

Monica Nizzardo, Chiara Simone, Federica Rizzo, Margherita Ruggieri, Sabrina Salani, Giulietta Riboldi, Irene Faravelli, Chiara Zanetta, Nereo Bresolin, Giacomo P. Comi, Stefania Corti

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of motor neurons. Currently, there is no effective therapy for ALS. Stem cell transplantation is a potential therapeutic strategy for ALS, and the reprogramming of adult somatic cells into induced pluripotentstemcells (iPSCs) represents a novel cell source. In this study, we isolated a specific neural stem cell (NSC) population from human iPSCs based on high aldehyde dehydrogenase activity, low side scatter and integrin VLA4 positivity. We assessed the therapeutic effects of these NSCs on the phenotype of ALSmice after intrathecal or intravenous injections. Transplanted NSCs migrated and engrafted into the central nervous system via both routes of injection. Compared with control ALS, treated ALS mice exhibited improved neuromuscular function and motor unit pathology and significantly increased life span, in particular with the systemic administration of NSCs (15%). These positive effects are linked to multiple mechanisms, including production of neurotrophic factors and reduction of micro-and macrogliosis. NSCs induced a decrease in astrocyte number through the activation of the vanilloid receptor TRPV1. We conclude that minimally invasive injections of iPSC-derived NSCs can exert a therapeutic effect in ALS. This study contributes to advancements in iPSC-mediated approaches for treating ALS and other neuro degenerative diseases.

Original languageEnglish
Pages (from-to)342-354
Number of pages13
JournalHuman Molecular Genetics
Volume23
Issue number2
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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