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Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease
Lee, Jean-Pyo,Jeyakumar, Mylvaganam,Gonzalez, Rodolfo,Takahashi, Hiroto,Lee, Pei-Jen,Baek, Rena C,Clark, Dan,Rose, Heather,Fu, Gerald,Clarke, Jonathan,McKercher, Scott,Meerloo, Jennifer,Muller, Franz- Nature Publishing Group 2007 Nature medicine Vol.13 No.4
Intracranial transplantation of neural stem cells (NSCs) delayed disease onset, preserved motor function, reduced pathology and prolonged survival in a mouse model of Sandhoff disease, a lethal gangliosidosis. Although donor-derived neurons were electrophysiologically active within chimeric regions, the small degree of neuronal replacement alone could not account for the improvement. NSCs also increased brain β-hexosaminidase levels, reduced ganglioside storage and diminished activated microgliosis. Additionally, when oral glycosphingolipid biosynthesis inhibitors (β-hexosaminidase substrate inhibitors) were combined with NSC transplantation, substantial synergy resulted. Efficacy extended to human NSCs, both to those isolated directly from the central nervous system (CNS) and to those derived secondarily from embryonic stem cells. Appreciating that NSCs exhibit a broad repertoire of potentially therapeutic actions, of which neuronal replacement is but one, may help in formulating rational multimodal strategies for the treatment of neurodegenerative diseases.