title: Human skeletal muscle stem cell antiinflammatory activity ameliorates clinical outcome in amyotrophic lateral sclerosis models.
abstract: Mesenchymal stem cell (MSC) therapy is considered one of the most promising approaches for treating different neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). We previously characterized a subpopulation of human skeletal muscle-derived stem cells (SkmSCs) with MSC-like characteristics that differentiate into the neurogenic lineage in vitro. In the present study, we evaluated the SkmSC therapeutic effects in the most characterized model of spontaneous motor neuron degeneration, the Wobbler (Wr) mouse. Before evaluating the therapeutic efficacy in the Wr mouse, we followed the route of Skm-SCs at different times after intracerebroventricular injection. Two exogenous tracers, superparamagnetic iron oxide (SPIO) nanoparticles and Hoechst 33258, were used for the in vivo and ex vivo tracking of SkmSCs. We found that the loading of both Hoechst and SPIO was not toxic and efficiently labeled SkmSCs. The magnetic resonance imaging (MRI) system 7 Tesla allowed us to localize transplanted SkmSCs along the whole ventricular system up to 18 wks after injection. The ex vivo Hoechst 33258 visualization confirmed the in vivo results obtained by MRI analyses. Behavioral observations revealed a fast and sustained improvement of motor efficacy in SkmSC-treated Wr mice associated with a relevant protection of functional neuromuscular junctions. Moreover, we found that in SkmSC-treated Wr mice, a significant increase of important human antiinflammatory cytokines occurred. This evidence is in accordance with previous findings showing the bystander effect of stem cell transplantation in neurodegenerative disorders and further strengthens the hypothesis of the possible link between inflammation, cytotoxicity and ALS.
authors.affiliation: Department of Cerebrovascular Disease, IRCCS Foundation, Neurological Institute "C. Besta," Milan, Italy. laura.canzi@istituto-besta.it
authors.forename: Laura
authors.initials: L
authors.lastname: Canzi
authors.forename: Valeria
authors.initials: V
authors.lastname: Castellaneta
authors.forename: Stefania
authors.initials: S
authors.lastname: Navone
authors.forename: Sara
authors.initials: S
authors.lastname: Nava
authors.forename: Marta
authors.initials: M
authors.lastname: Dossena
authors.forename: Ileana
authors.initials: I
authors.lastname: Zucca
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mennini
authors.forename: Paolo
authors.initials: P
authors.lastname: Bigini
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Parati
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000473:pathology; D018482:Muscle, Skeletal / Q000166:cytology*; D013116:Spinal Cord / Q000473:pathology; D033581:Stem Cell Transplantation
chemical_list: D016207:Cytokines
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