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a Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan;
b Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe, Japan
Key Words. Fluorescence-activated cell sorting • Embryonic stem cell • Sox1 • Teratoma • Transplantation • Dopaminergic neuron
Correspondence: Jun Takahashi, M.D., Ph.D., Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54, Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Telephone: #81-75-751-3450; Fax: #81-75-752-9501; e-mail: jbtaka{at}kuhp.kyoto-u.ac.jp
Received March 29, 2005;
accepted for publication October 2, 2005.
The differentiation of dopaminergic (DA) neurons from mouse embryonic stem cells (ESCs) 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 ESC transplantation is the propensity of ESC-derived grafts to form tumors in vivo. To address this problem, we used fluorescence-activated cell sorting to purify mouse ESC-derived neural precursors expressing the neural precursor marker Sox1. ESC-derived, Sox1+ 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– cells that expressed ESC markers frequently formed tumors in vivo. These results indicate that Sox1-based cell sorting of neural precursors prevents graft-derived tumor formation after transplantation, providing a promising strategy for cell transplantation therapy of neurodegenerative disorders.
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