Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia
Mesenchymal stem cells have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Of these, cerebellar ataxia is a group of disorders characterized by the degeneration of the cerebellum, particularly the Purkinje cells, respon...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996110002251 |
| _version_ | 1818675626962321408 |
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| author | Jonathan Jones Jesús Jaramillo-Merchán Carlos Bueno Diego Pastor MariCarmen Viso-León Salvador Martínez |
| author_facet | Jonathan Jones Jesús Jaramillo-Merchán Carlos Bueno Diego Pastor MariCarmen Viso-León Salvador Martínez |
| author_sort | Jonathan Jones |
| collection | DOAJ |
| description | Mesenchymal stem cells have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Of these, cerebellar ataxia is a group of disorders characterized by the degeneration of the cerebellum, particularly the Purkinje cells, responsible for motor coordination and control of the motor functions. To analyze the possibility of using bone marrow-derived mesenchymal stem cells in treating ataxia, we transplanted these cells in the cerebellum of newborn Lurcher mutant mice, a very aggressive mouse model characterized by the selective early post-natal death of Purkinje cells in the cerebellum. Two months after the surgical procedure, the treated mice presented significant improvements in the motor behavior tests performed. Histological analysis of the cerebellum indicated that the donor cells had migrated throughout the cerebellum, as well as a significant increase in the number of Purkinje cells. Many grafted stem cells were located adjacent to the Purkinje cell layer, and expressed BDNF, NT-3 or GDNF, neurotrophic factors implicated in Purkinje cell survival. Also, a small percentage of the grafted stem cells had fused with Purkinje cells. Thus, we have shown that mesenchymal stem cells are capable of integrating into the central nervous system, migrate towards the areas where neurodegenerative processes are occurring, and rescue the degenerating cells through cell trophic effects. This is an adequate and feasible model that could be translated into a therapeutic approach for clinical assays in neurodegenerative diseases. |
| first_indexed | 2024-12-17T08:30:35Z |
| format | Article |
| id | doaj.art-9f546ec7ef0a4d4889e605e36f610e6e |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T08:30:35Z |
| publishDate | 2010-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-9f546ec7ef0a4d4889e605e36f610e6e2022-12-21T21:56:38ZengElsevierNeurobiology of Disease1095-953X2010-11-01402415423Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxiaJonathan Jones0Jesús Jaramillo-Merchán1Carlos Bueno2Diego Pastor3MariCarmen Viso-León4Salvador Martínez5Corresponding author. Fax: +34 965919555.; Neuroscience Institute, University Miguel Hernandez (UMH-CSIC), Crtra. Valencia N. 322, San Juan, Alicante, Spain, 03550Neuroscience Institute, University Miguel Hernandez (UMH-CSIC), Crtra. Valencia N. 322, San Juan, Alicante, Spain, 03550Neuroscience Institute, University Miguel Hernandez (UMH-CSIC), Crtra. Valencia N. 322, San Juan, Alicante, Spain, 03550Neuroscience Institute, University Miguel Hernandez (UMH-CSIC), Crtra. Valencia N. 322, San Juan, Alicante, Spain, 03550Neuroscience Institute, University Miguel Hernandez (UMH-CSIC), Crtra. Valencia N. 322, San Juan, Alicante, Spain, 03550Neuroscience Institute, University Miguel Hernandez (UMH-CSIC), Crtra. Valencia N. 322, San Juan, Alicante, Spain, 03550Mesenchymal stem cells have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Of these, cerebellar ataxia is a group of disorders characterized by the degeneration of the cerebellum, particularly the Purkinje cells, responsible for motor coordination and control of the motor functions. To analyze the possibility of using bone marrow-derived mesenchymal stem cells in treating ataxia, we transplanted these cells in the cerebellum of newborn Lurcher mutant mice, a very aggressive mouse model characterized by the selective early post-natal death of Purkinje cells in the cerebellum. Two months after the surgical procedure, the treated mice presented significant improvements in the motor behavior tests performed. Histological analysis of the cerebellum indicated that the donor cells had migrated throughout the cerebellum, as well as a significant increase in the number of Purkinje cells. Many grafted stem cells were located adjacent to the Purkinje cell layer, and expressed BDNF, NT-3 or GDNF, neurotrophic factors implicated in Purkinje cell survival. Also, a small percentage of the grafted stem cells had fused with Purkinje cells. Thus, we have shown that mesenchymal stem cells are capable of integrating into the central nervous system, migrate towards the areas where neurodegenerative processes are occurring, and rescue the degenerating cells through cell trophic effects. This is an adequate and feasible model that could be translated into a therapeutic approach for clinical assays in neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S0969996110002251Mesenchymal stem cellsLurcher mouseCerebellar ataxiaNeurotrophic effectPurkinje cellsBone marrow |
| spellingShingle | Jonathan Jones Jesús Jaramillo-Merchán Carlos Bueno Diego Pastor MariCarmen Viso-León Salvador Martínez Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia Neurobiology of Disease Mesenchymal stem cells Lurcher mouse Cerebellar ataxia Neurotrophic effect Purkinje cells Bone marrow |
| title | Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia |
| title_full | Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia |
| title_fullStr | Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia |
| title_full_unstemmed | Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia |
| title_short | Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia |
| title_sort | mesenchymal stem cells rescue purkinje cells and improve motor functions in a mouse model of cerebellar ataxia |
| topic | Mesenchymal stem cells Lurcher mouse Cerebellar ataxia Neurotrophic effect Purkinje cells Bone marrow |
| url | http://www.sciencedirect.com/science/article/pii/S0969996110002251 |
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