Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation.
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.
Fukuda
Hitoshi
H
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54, Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Takahashi
Jun
J
Watanabe
Kiichi
K
Hayashi
Hideki
H
Morizane
Asuka
A
Koyanagi
Masaomi
M
Sasai
Yoshiki
Y
Hashimoto
Nobuo
N
D000818:Animals; D000943:Antigens, Differentiation; D020295:Brain Stem Neoplasms / Q000209:etiology; D002454:Cell Differentiation / Q000502:physiology*; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry / Q000379:methods; D006609:High Mobility Group Proteins; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D010300:Parkinson Disease / Q000628:therapy; D055748:SOXB1 Transcription Factors; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse