Sertoli cells improve survival of motor neurons in SOD1 transgenic mice, a model of amyotrophic lateral sclerosis.
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.
Hemendinger
Richelle
R
Carolinas Neuromuscular/ALS-MDA Center, Division of Neurology, Carolinas Medical Center, 1000 Blythe Blvd, Charlotte, NC 28203, USA.
Wang
Jay
J
Malik
Saafan
S
Persinski
Rafal
R
Copeland
Jane
J
Emerich
Dwaine
D
Gores
Paul
P
Halberstadt
Craig
C
Rosenfeld
Jeffrey
J
D000690:Amyotrophic Lateral Sclerosis / Q000601:surgery*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D050991:GATA4 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology* / Q000637:transplantation; D009414:Nerve Growth Factors / Q000378:metabolism; D012708:Sertoli Cells / Q000502:physiology* / Q000637:transplantation*; D013116:Spinal Cord / Q000166:cytology / Q000601:surgery; D013482:Superoxide Dismutase / Q000235:genetics
D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D009414:Nerve Growth Factors; D004247:DNA; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase