Journal
NEUROBIOLOGY OF DISEASE
Volume 40, Issue 2, Pages 415-423Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.07.001
Keywords
Mesenchymal stem cells; Lurcher mouse; Cerebellar ataxia; Neurotrophic effect; Purkinje cells; Bone marrow; Cell fusion
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Funding
- Generalitat Valenciana [INA-SM-00108, APOSTD/2007/016, 6]
- Consolider-Ingenio [CSD2007-00023]
- ELA Foundation [U01/07]
- TERCEL [RD06/0010/0023]
- Spanish National Research Council [5321617002-B10001A201]
- PROMETEO [/2009/028]
- Ministry of Education and Science [BFU2005-0985]
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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. (c) 2010 Elsevier Inc. All rights reserved.
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