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

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.

• Authors: 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
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 13 Issue 3 Pg. 548-55 (Mar 2006) ISSN: 1525-0016 [Print] United States
• PMID: 16316785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucuronidase

Topics

• Animals
• Animals, Newborn
• Behavior, Animal (physiology)
• Brain (enzymology, pathology)
• Embryonic Stem Cells (enzymology, metabolism, transplantation)
• Genetic Therapy
• Glucuronidase (analysis, genetics, metabolism)
• Hearing (genetics)
• Lysosomes (enzymology)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Transgenic
• Mucopolysaccharidosis VII (pathology, physiopathology, therapy)
• Neurons (enzymology, metabolism)
• Protein Transport (genetics)
• Stem Cell Transplantation
• Telencephalon (physiopathology)