title: Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model.
abstract: Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination.
authors.affiliation: Neuroscience Institute, University Miguel Hernández - Spanish Council for Scientific Research (UMH-CSIC), Alicante, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Cruz-Martinez
authors.affiliation: Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: González-Granero
authors.affiliation: Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, Spain.
authors.forename: M M
authors.initials: MM
authors.lastname: Molina-Navarro
authors.affiliation: Neuroscience Institute, University Miguel Hernández - Spanish Council for Scientific Research (UMH-CSIC), Alicante, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pacheco-Torres
authors.affiliation: Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: García-Verdugo
authors.affiliation: Neuroscience Institute, University Miguel Hernández - Spanish Council for Scientific Research (UMH-CSIC), Alicante, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Geijo-Barrientos
authors.affiliation: Neuroscience Institute, University Miguel Hernández - Spanish Council for Scientific Research (UMH-CSIC), Alicante, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.affiliation: Neuroscience Institute, University Miguel Hernández - Spanish Council for Scientific Research (UMH-CSIC), Alicante, Spain.|IMIB-Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Martinez
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003337:Corpus Callosum / Q000378:metabolism / Q000648:ultrastructure; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid / Q000235:genetics; D020547:Lateral Ventricles / Q000378:metabolism / Q000648:ultrastructure; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D003471:Cuprizone