TY - JOUR
T1 - Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation
AU - Fukuda, Hitoshi
AU - Takahashi, Jun
AU - Watanabe, Kiichi
AU - Hayashi, Hideki
AU - Morizane, Asuka
AU - Koyanagi, Masaomi
AU - Sasai, Yoshiki
AU - Hashimoto, Nobuo
PY - 2006/3
Y1 - 2006/3
N2 - 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. ESCderived, 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.
AB - 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. ESCderived, 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.
KW - Dopaminergic neuron
KW - Embryonic stem cell
KW - Fluorescence-activated cell sorting
KW - Sox1
KW - Teratoma Transplantation
UR - http://www.scopus.com/inward/record.url?scp=33745001244&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745001244&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2005-0137
DO - 10.1634/stemcells.2005-0137
M3 - Article
C2 - 16223855
AN - SCOPUS:33745001244
SN - 1066-5099
VL - 24
SP - 763
EP - 771
JO - Stem Cells
JF - Stem Cells
IS - 3
ER -