| Co-Investigator(Kenkyū-buntansha) |
YAMANOUCHI Hideo Dokkyo University School of Medicine, Department of Pediatrics, Associate Professor, 医学部, 助教授 (10250226)
NAKAGAWA Eiji National Institute of Neuroscience, National Center of Neurology and Psychiatry, Department of Mental Retardation and Birth Defect Research, Research fellow, 神経研究所・疾病研究第2部, 研究員 (70333002)
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| Research Abstract |
We have generated self-renewing and multipotent human neural stem cells (NSCs) via retrovirus-mediated v-myc transfer into embryonic human brain cells, and have isolated several clonal cell lines. These lines can be maintained in an undifferentiated state, or induced to differentiate by changing the culture conditions. One of these cell lines, HB1/C4, is genetically modified NSCs maintained as a stable cell line in serum-free medium remains uncommited, undifferentiated, multipotent and express phenotypes specific for NSCs such as nestin, musashi and vimentin.
When NB1/C4 cells were grown in a serum containing medium (5% fetal bovine serum and 5% equine serum), several differentiated cell types, which are known as progeny of NSCs such as neurons, astrocytes and oligodendrocytes were induced in culture.
To investigate the fate of HB1/C4 cells in a myelin deficiency structure, we grafted NB1/C4 cells into the brain of adult or neonatal myelin mutant shiverer mouse. HB1/C4 cells were found to migrate extensively from the site of implantation into other anatomical sites and to remyelinate formerly unmyelinated axons. The ability of the HB1/C4 cells, human immortalized NSCs, to respond in vitro to guidance cues and signals that can direct their differentiation along multiple phenotypic pathways suggests that they can providea powerful and virtually unlimitted source of cells for gene cell therapy in the human neurological diseases.
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