Intracerebral cell transplantation therapy for murine GM1 gangliosidosis.
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.
Sawada
Tomo
T
Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Tanaka
Akemi
A
Higaki
Katsumi
K
Takamura
Ayumi
A
Nanba
Eiji
E
Seto
Toshiyuki
T
Maeda
Mitsuyo
M
Yamaguchi
Etsuko
E
Matsuda
Junichiro
J
Yamano
Tunekazu
T
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
D001616:beta-Galactosidase