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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

The therapeutic potential of neural stem/progenitor cells in murine globoid cell leukodystrophy is conditioned by macrophage/microglia activation.

Twitcher (GALC(twi/twi)) is the murine model of globoid cell leukodystrophy (GLD or Krabbe disease), a disease caused by mutations of the lysosomal enzyme galactocerebrosidase (GALC). To verify the therapeutic potential on twitcher of neural stem/progenitor cells (NSPC), we transduced them with a GALC lentiviral vector. Brain injection of NSPC-GALC increased survival of GALC(twi/twi) from 36.1 +/- 4.1 to 52.2 +/- 5.6 days (P < 0.0001). Detection of GALC activity and flow cytometry showed that NSPC-GALC and NSPC expressing the green fluorescent protein were attracted to the posterior area of twitcher brain, where demyelination occurs first. GALC(twi/twi) microglia, also more abundant in posterior regions of the brain, released significant amounts of the cytotoxic cytokine TNF-alpha when matched with NSPC-GALC. Thus, in murine GLD, and possibly in other demyelinating diseases, NSPC are attracted to regions of active demyelination but have limited survival and therapeutic potential if attacked by activated macrophages/microglia.[1]

References

  1. The therapeutic potential of neural stem/progenitor cells in murine globoid cell leukodystrophy is conditioned by macrophage/microglia activation. Pellegatta, S., Tunici, P., Poliani, P.L., Dolcetta, D., Cajola, L., Colombelli, C., Ciusani, E., Di Donato, S., Finocchiaro, G. Neurobiol. Dis. (2006) [Pubmed]
 
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