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

Serena Pellegatta, Patrizia Tunici, Pietro Luigi Poliani, Diego Dolcetta, Laura Cajola, Cristina Colombelli, Emilio Ciusani, Stefano Di Donato, Gaetano Finocchiaro

Research output: Contribution to journalArticle


Twitcher (GALCtwi/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 GALCtwi/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. GALCtwi/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.

Original languageEnglish
Pages (from-to)314-323
Number of pages10
JournalNeurobiology of Disease
Issue number2
Publication statusPublished - Feb 2006



  • Cell therapy
  • Leukodystrophy
  • Microglia
  • Neural stem cells
  • TNF-alpha

ASJC Scopus subject areas

  • Neurology

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