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

Abstract

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
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2006

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Galactosylceramidase
Globoid Cell Leukodystrophy
Neural Stem Cells
Macrophage Activation
Microglia
Stem Cells
Demyelinating Diseases
Brain
Therapeutics
Green Fluorescent Proteins
Flow Cytometry
Tumor Necrosis Factor-alpha
Macrophages
Cytokines
Mutation
Injections
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Neurology

Cite this

The therapeutic potential of neural stem/progenitor cells in murine globoid cell leukodystrophy is conditioned by macrophage/microglia activation. / Pellegatta, Serena; Tunici, Patrizia; Poliani, Pietro Luigi; Dolcetta, Diego; Cajola, Laura; Colombelli, Cristina; Ciusani, Emilio; Di Donato, Stefano; Finocchiaro, Gaetano.

In: Neurobiology of Disease, Vol. 21, No. 2, 02.2006, p. 314-323.

Research output: Contribution to journalArticle

Pellegatta, Serena ; Tunici, Patrizia ; Poliani, Pietro Luigi ; Dolcetta, Diego ; Cajola, Laura ; Colombelli, Cristina ; Ciusani, Emilio ; Di Donato, Stefano ; Finocchiaro, Gaetano. / The therapeutic potential of neural stem/progenitor cells in murine globoid cell leukodystrophy is conditioned by macrophage/microglia activation. In: Neurobiology of Disease. 2006 ; Vol. 21, No. 2. pp. 314-323.
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