Neural stem cell implantation extends life in Niemann-Pick C1 mice
In order to evaluate the phenotypic effects of implanted neural stem cells (NSCs) in the mouse model of Niemann-Pick C (NPC) disease, we injected a well-characterized clone of murine NSCs into the cerebella of neonatalNpc1 − /− and control mice. The implanted cells survived and were abundant in some regions of the cerebellum. Life span was lengthened in NPC mice with the implanted NSCs. However, the rate of weight gain and subsequent weight loss, resulting from neurodegeneration, was not significantly different from un-injected controls. Ataxia was measured by Rota-Rod performance. The overall rate of decline in time on the Rota-Rod was not significantly slowed down. Thus, in this small group of NPC mice, a single administration in the neonatal period of the NSCs (which were not engineered to over-express the missing gene and not directed into the parenchyma) was only partially therapeutic.
Keywordscerebellum disease neurodegeneration neurons neuroprotection Niemann-Pick Purkinje cells stem cells stem cell transplantation type C
Unable to display preview. Download preview PDF.
- Ko DC, Milenkovic L, Beier SM, Manuel H, Buchanan J, Scott MP, 2005. Cell-autonomous death of cerebellar Purkinje neurons with autophagy in Niemann-Pick type C disease. PLOS Genet 1e7: 0082–0095.Google Scholar
- Rosario CM, Yandava BD, Kosaras B, Zurakowski D, Sidman RL, Snyder EY, 1997. Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action. Development 124: 4213–4224.PubMedGoogle Scholar
- Taylor RM, Lee JP, Palacino JL, Bower KA, Li J, Vanier MT, et al. 2006. Intrinsic resistance of neural stem cells to toxic metabolites may make them well suited for cell non-autonomous disorders: evidence from a mouse model of Krabbe leukodystrophy. J Neurochem 97: 1585–1599.CrossRefPubMedGoogle Scholar