TY - JOUR
T1 - Regeneration of the central nervous system using iPS cell-technologies
AU - Okano, Hideyuki
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2009
Y1 - 2009
N2 - Induced pluripotent stem (iPS) cells are pluripotent stem cells directly reprogrammed from cultured mouse fibroblast by introducing Oct3/4, Sox2, c-Myc, and Klf4. Cells obtained using this technology, which allows the ethical issues and immunological rejection associated with embryonic stem (ES) cells to be avoided, might be a clinically useful source for cell replacement therapies. We found that secondary neurospheres (SNSs) generated from various mouse iPS cell showed their neural differentiation capacity and teratoma formation after transplantation into the brain of immunodeficient NOD/SCID mice. We found that origin (source of somatic cells) of the iPS cells are the crucial determinant for the potential tumorigenicity of iPS-derived neural stem/progenitor cells and that their tumorigenicity results from the persistent presence of undifferentiated cells within the SNSs. Surprisingly, SNSs derived from c-Myc minusiPS cells generated without drug selection showed robust tumorigenesis, in spite of their potential to contribute adult chimeric mice without tumor formation. Furthermore, we examined whether the transplantation of non-tumorigenic Nanog-iPS-derived SNSs into mouse spinal cord injury (SCI) model could promote locomotor function recovery. As a result, we found that properly pre-evaluated iPS clone-derived neural stem/progenitor cells may be a promising cell source for future transplantation therapy of SCI.
AB - Induced pluripotent stem (iPS) cells are pluripotent stem cells directly reprogrammed from cultured mouse fibroblast by introducing Oct3/4, Sox2, c-Myc, and Klf4. Cells obtained using this technology, which allows the ethical issues and immunological rejection associated with embryonic stem (ES) cells to be avoided, might be a clinically useful source for cell replacement therapies. We found that secondary neurospheres (SNSs) generated from various mouse iPS cell showed their neural differentiation capacity and teratoma formation after transplantation into the brain of immunodeficient NOD/SCID mice. We found that origin (source of somatic cells) of the iPS cells are the crucial determinant for the potential tumorigenicity of iPS-derived neural stem/progenitor cells and that their tumorigenicity results from the persistent presence of undifferentiated cells within the SNSs. Surprisingly, SNSs derived from c-Myc minusiPS cells generated without drug selection showed robust tumorigenesis, in spite of their potential to contribute adult chimeric mice without tumor formation. Furthermore, we examined whether the transplantation of non-tumorigenic Nanog-iPS-derived SNSs into mouse spinal cord injury (SCI) model could promote locomotor function recovery. As a result, we found that properly pre-evaluated iPS clone-derived neural stem/progenitor cells may be a promising cell source for future transplantation therapy of SCI.
KW - Embryonic stem cells (ES cells)
KW - Induced pluripotent stem cells (iPS cells)
KW - Neural stem cells
KW - Spinal cord injury
KW - Tumorigenicity
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U2 - 10.5692/clinicalneurol.49.825
DO - 10.5692/clinicalneurol.49.825
M3 - Article
C2 - 20030221
AN - SCOPUS:77956220303
VL - 49
SP - 825
EP - 826
JO - Clinical Neurology
JF - Clinical Neurology
SN - 0009-918X
IS - 11
ER -