title: Mesenchymal stem cells improve motor functions and decrease neurodegeneration in ataxic mice.
abstract: The main objective of this work is to demonstrate the feasibility of using bone marrow-derived stem cells in treating a neurodegenerative disorder such as Friedreich's ataxia. In this disease, the dorsal root ganglia of the spinal cord are the first to degenerate. Two groups of mice were injected intrathecally with mesenchymal stem cells isolated from either wild-type or Fxntm1Mkn/Tg(FXN)YG8Pook (YG8) mice. As a result, both groups presented improved motor skills compared to nontreated mice. Also, frataxin expression was increased in the dorsal root ganglia of the treated groups, along with lower expression of the apoptotic markers analyzed. Furthermore, the injected stem cells expressed the trophic factors NT3, NT4, and BDNF, which bind to sensory neurons of the dorsal root ganglia and increase their survival. The expression of antioxidant enzymes indicated that the stem cell-treated mice presented higher levels of catalase and GPX-1, which are downregulated in the YG8 mice. There were no significant differences in the use of stem cells isolated from wild-type and YG8 mice. In conclusion, bone marrow mesenchymal stem cell transplantation, both autologous and allogeneic, is a feasible therapeutic option to consider in delaying the neurodegeneration observed in the dorsal root ganglia of Friedreich's ataxia patients.
authors: Neuroscience Institute, University Miguel Hernández (UMH-CSIC), San Juan, Alicante, Spain.
authors: Jonathan
authors: J
authors: Jones
authors: Neuroscience Institute, University Miguel Hernández (UMH-CSIC), San Juan, Alicante, Spain.
authors: Alicia
authors: A
authors: Estirado
authors: Neuroscience Institute, University Miguel Hernández (UMH-CSIC), San Juan, Alicante, Spain.
authors: Carolina
authors: C
authors: Redondo
authors: Neuroscience Institute, University Miguel Hernández (UMH-CSIC), San Juan, Alicante, Spain.
authors: Jesus
authors: J
authors: Pacheco-Torres
authors: 1] Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, Valencia, Spain [2] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: Maria-Salomé
authors: MS
authors: Sirerol-Piquer
authors: 1] Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, Valencia, Spain [2] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: José M
authors: JM
authors: Garcia-Verdugo
authors: 1] Neuroscience Institute, University Miguel Hernández (UMH-CSIC), San Juan, Alicante, Spain [2] IMIB-Hospital Universitario Virgen de la Arrixaca, Univ. Murcia, Murcia, Spain.
authors: Salvador
authors: S
authors: Martinez
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007278:Injections, Spinal; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D000094765:Glutathione Peroxidase GPX1; D000096923:Frataxin
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002374:Catalase; D005979:Glutathione Peroxidase; D033862:Iron-Binding Proteins; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D000094765:Glutathione Peroxidase GPX1; D000096923:Frataxin; C073922:neurotrophin 4; C000722068:Gpx1 protein, mouse