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Sertoli cells improve survival of motor neurons in SOD1 transgenic mice, a model of amyotrophic lateral sclerosis.
- Source :
-
Experimental neurology [Exp Neurol] 2005 Dec; Vol. 196 (2), pp. 235-43. Date of Electronic Publication: 2005 Oct 18. - Publication Year :
- 2005
-
Abstract
- Cell replacement therapy has been widely suggested as a treatment for multiple diseases including motor neuron disease. A variety of donor cells have been tested for treatment including isolated preparations from bone marrow and embryonic spinal cord. Another cell source, Sertoli cells, have been successfully used in models of diabetes, Parkinson's disease and Huntington's disease. The ability of these cells to secrete cytoprotective proteins and their role as 'nurse cells' supporting the function of other cell types in the testes suggest their potential use as neuroprotective cells. The current study examines the ability of Sertoli cells injected into the parenchyma of the spinal cord to protect motor neurons in a mouse model for amyotrophic lateral sclerosis. Seventy transgenic mice expressing the mutant (G93A) human Cu-Zn superoxide dismutase (SOD1) received a unilateral spinal injection of Sertoli-enriched testicular cells into the L4-L5 ventral horn (1 x 10(5) cells total) prior to the onset of clinical symptoms. The animals were euthanized at the end stage of the disease. Histological and morphometric analyses of the transplant site were performed. A significant increase in the number of surviving ChAT positive motor neurons was found ipsilateral to the injection compared with contralateral and uninjected spinal cord. The ipsilateral increase in motor neuron density was dependent upon proximity to the injection site. Sections rostral or caudal to the injection site did not display a similar difference in motor neuron density. Implantation of a Sertoli-cell-enriched preparation has a significant neuroprotective benefit to vulnerable motor neurons in the SOD1 transgenic model. The therapeutic benefit may be the result of secreted neurotrophic factors present at a critical stage of motor neuron degeneration in this model.
- Subjects :
- Animals
Blotting, Western methods
Cell Count
Cell Survival physiology
Cells, Cultured
Choline O-Acetyltransferase metabolism
DNA analysis
Female
Functional Laterality
GATA4 Transcription Factor metabolism
Gene Expression Regulation physiology
Humans
Immunohistochemistry methods
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motor Neurons transplantation
Nerve Growth Factors metabolism
Spinal Cord cytology
Spinal Cord surgery
Superoxide Dismutase genetics
Amyotrophic Lateral Sclerosis surgery
Disease Models, Animal
Motor Neurons physiology
Sertoli Cells physiology
Sertoli Cells transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 0014-4886
- Volume :
- 196
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 16242126
- Full Text :
- https://doi.org/10.1016/j.expneurol.2005.07.025