| Literature DB >> 16199167 |
Serena Pellegatta1, Patrizia Tunici, Pietro Luigi Poliani, Diego Dolcetta, Laura Cajola, Cristina Colombelli, Emilio Ciusani, Stefano Di Donato, Gaetano Finocchiaro.
Abstract
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.Entities:
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Year: 2005 PMID： 16199167 DOI： 10.1016/j.nbd.2005.07.016
Source DB: PubMed Journal: Neurobiol Dis ISSN： 0969-9961 Impact factor: 5.996