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Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells
Christine Varela, … , Marc Peschanski, Nathalie Lefort
Christine Varela, … , Marc Peschanski, Nathalie Lefort
Published January 24, 2012
Citation Information: J Clin Invest. 2012;122(2):569-574. https://doi.org/10.1172/JCI46268.
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Research Article

Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

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Abstract

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines.

Authors

Christine Varela, Jérôme Alexandre Denis, Jérôme Polentes, Maxime Feyeux, Sophie Aubert, Benoite Champon, Geneviève Piétu, Marc Peschanski, Nathalie Lefort

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Figure 1

Characterization of the neural derivatives of the VUB03-DM1 cell line.

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Characterization of the neural derivatives of the VUB03-DM1 cell line.
(...
(A) Morphological features of NSCs at passage 48 derived from VUB03-DM1. (B and C) VUB03-DM1 passage 48 NSCs expressed the neural marker SOX2. Note that cells did not express the neuron-specific ELAV/Hu family members HuC, HuD (HuCD) (B) and TUBB3 (C). (D) Morphological features of neurons derived from VUB03-DM1 passage 48 NSCs. (E and F) Neurons expressing the neuronal markers HuCD (E) and TUBB3 (F) generated after 20 days of differentiation from VUB03-DM1 passage 48 NSCs. Scale bars: 20 μm.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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