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Original Article |
1 Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
2 Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe, Japan
* To whom correspondence should be addressed. E-mail: jbtaka{at}kuhp.kyoto-u.ac.jp.
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Abstract |
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The differentiation of dopaminergic (DA) neurons from mouse embryonic stem (ES) cells can be efficiently induced, making these neurons a potential source for transplantation as a treatment for Parkinson's disease, a condition characterized by the gradual loss of midbrain DA neurons. One of the major persistent obstacles to the successful implementation of therapeutic ES cell transplantation is the propensity of ES cell-derived grafts to form tumors in vivo. To address this problem, we purified by fluorescence-activated cell sorting (FACS) mouse ES cell-derived neural precursors expressing the neural precursor marker Sox1. ES cell-derived, Sox1-positive cells began to express neuronal cell markers and differentiated into DA neurons upon transplantation into mouse brains, but did not generate tumors in this site. In contrast, Sox1-negative cells that expressed ES cell markers frequently formed tumors in vivo. These results indicate that Sox1-based cell sorting of neural precursors prevents graft-derived tumor formation following transplantation, providing a promising strategy for cell transplantation therapy of neurodegenerative disorders.
Key Words. FACS, ES cell, Sox1, teratoma, transplantation, dopaminergic neuron
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