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: Tomo Sawada, Akemi Tanaka, Katsumi Higaki, Ayumi Takamura, Eiji Nanba, Toshiyuki Seto, Mitsuyo Maeda, Etsuko Yamaguchi, Junichiro Matsuda, Tunekazu Yamano
• Journal: Brain & development (Brain Dev) Vol. 31 Issue 10 Pg. 717-24 (Nov 2009) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 19118961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• beta-Galactosidase

Topics

• Animals
• Blotting, Western
• Brain Tissue Transplantation
• Cells, Cultured
• Cerebral Cortex (transplantation)
• Fetal Tissue Transplantation
• Gangliosidosis, GM1 (genetics, therapy)
• Humans
• Mesenchymal Stem Cell Transplantation
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• beta-Galactosidase (genetics, metabolism)