Histopathological and behavioral improvement of murine mucopolysaccharidosis type VII by intracerebral transplantation of neural stem cells

Yasuyuki Fukuhara, Xiao Kang Li, Yusuke Kitazawa, Masumi Inagaki, Kentaro Matsuoka, Motomichi Kosuga, Rika Kosaki, Takuya Shimazaki, Hitoshi Endo, Akihiro Umezawa, Hideyuki Okano, Takao Takahashi, Torayuki Okuyama

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The therapeutic efficacy of neural stem cell transplantation for central nervous system (CNS) lesions in lysosomal storage disorders was explored using a murine model of mucopolysaccharidosis type VII (MPS VII). We used fetal neural stem cells derived from embryonic mouse striata and expanded in vitro by neurosphere formation as the source of graft materials. We transplanted neurospheres into the lateral ventricles of newborn MPS VII mice and found that donor cells migrated far beyond the site of injection within 24 h, and some of them could reach the olfactory bulb. A quantitative measurement indicated that the GUSB activity in the brain was 12.5 to 42.3% and 5.5 to 6.3% of normal activity at 24 h and 3 weeks after transplantation. In addition, histological analysis revealed a widespread decrease in lysosomal storage in the recipient's hippocampus, cortex, and ependyma. A functional assessment with novel-object recognition tests confirmed improvements in behavioral patterns. These results suggest that intracerebral transplantation of neural stem cells is feasible for treatment of CNS lesions associated with lysosomal storage disorders.

Original languageEnglish
Pages (from-to)548-555
Number of pages8
JournalMolecular Therapy
Volume13
Issue number3
DOIs
Publication statusPublished - 2006 Mar 1

Keywords

  • Intracerebral transplantation
  • Mucopolysaccharidosis type VII
  • Neurosphere

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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