title: 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.affiliation: Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fukuhara
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kitazawa
authors.forename: Masumi
authors.initials: M
authors.lastname: Inagaki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Motomichi
authors.initials: M
authors.lastname: Kosuga
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Shimazaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000201:enzymology / Q000473:pathology; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000378:metabolism / Q000637:transplantation; D015316:Genetic Therapy; D005966:Glucuronidase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006309:Hearing / Q000235:genetics; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016538:Mucopolysaccharidosis VII / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D033581:Stem Cell Transplantation; D013687:Telencephalon / Q000503:physiopathology*
chemical_list: D005966:Glucuronidase