Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-04

AUTHORS

Jean-Pyo Lee, Mylvaganam Jeyakumar, Rodolfo Gonzalez, Hiroto Takahashi, Pei-Jen Lee, Rena C Baek, Dan Clark, Heather Rose, Gerald Fu, Jonathan Clarke, Scott McKercher, Jennifer Meerloo, Franz-Josef Muller, Kook In Park, Terry D Butters, Raymond A Dwek, Philip Schwartz, Gang Tong, David Wenger, Stuart A Lipton, Thomas N Seyfried, Frances M Platt, Evan Y Snyder

ABSTRACT

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 beta-hexosaminidase levels, reduced ganglioside storage and diminished activated microgliosis. Additionally, when oral glycosphingolipid biosynthesis inhibitors (beta-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. More... »

PAGES

439-447

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm1548

DOI

http://dx.doi.org/10.1038/nm1548

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049016158

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17351625


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