title: Intracerebral cell transplantation therapy for murine GM1 gangliosidosis.
abstract: We performed a cell transplantation study to treat the brain involvement in lysosomal storage diseases. We used acid beta-galactosidase knock-out mice (BKO) from C57BL/6 as recipients. To minimize immune responses, we used cells derived from transgenic mice of C57BL/6 overexpressing the normal human beta-galactosidase. Fetal brain cells (FBC), bone marrow-derived mesenchymal stem cells (MSC), and mixed FBC and MSC cells were prepared and injected into the ventricle of newborn BKO mouse brain. The mice were examined at 1, 2, 4, and 8 weeks and 6 months after injection. In each experiment, the injected cells migrated into the whole brain effectively and survived for at least 8 weeks. Decrease in ganglioside GM1 level was also observed. FBC could survive for 6 months in recipient brain. However, the number of transplanted FBC decreased. In the brains of MSC- or mixed cell-treated mice, no grafted cells could be found at 6 months. To achieve sufficient long-term effects on the brain, a method of steering the immune response away from cytotoxic responses or of inducing tolerance to the products of therapeutic genes must be developed.
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Tomo
authors.initials: T
authors.lastname: Sawada
authors.forename: Akemi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Katsumi
authors.initials: K
authors.lastname: Higaki
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takamura
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Seto
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Maeda
authors.forename: Etsuko
authors.initials: E
authors.lastname: Yamaguchi
authors.forename: Junichiro
authors.initials: J
authors.lastname: Matsuda
authors.forename: Tunekazu
authors.initials: T
authors.lastname: Yamano
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016380:Brain Tissue Transplantation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000637:transplantation*; D016332:Fetal Tissue Transplantation; D016537:Gangliosidosis, GM1 / Q000235:genetics / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase