Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors
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Author(s) • • • • • • • • •
Soldner, Frank
Hockemeyer, Dirk
Beard, Caroline
Gao, Qing
Bell, George W.
Cook, Elizabeth G.
Hargus, Gunnar
Blak, Alexandra
Cooper, Oliver
Mitalipova, Maisam
Date Issued
March 2009
Journal
Cell
Publisher
Elsevier B.V.
Citation
Soldner, Frank, Dirk Hockemeyer, Caroline Beard, Qing Gao, George W. Bell, Elizabeth G. Cook, Gunnar Hargus, et al. “Parkinson’s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors.” Cell 136, no. 5 (March 2009): 964–977. © 2009 Elsevier Inc.
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Final published version
Abstract
Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients represent a powerful tool for biomedical research and may provide a source for replacement therapies. However, the use of viruses encoding the reprogramming factors represents a major limitation of the current technology since even low vector expression may alter the differentiation potential of the iPSCs or induce malignant transformation. Here, we show that fibroblasts from five patients with idiopathic Parkinson's disease can be efficiently reprogrammed and subsequently differentiated into dopaminergic neurons. Moreover, we derived hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Factor-free hiPSCs maintain a pluripotent state and show a global gene expression profile, more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2009.02.013