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Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors
Frank Soldner1,4,Dirk Hockemeyer1,4,Caroline Beard1,Qing Gao1,George W. Bell1,Elizabeth G. Cook1,Gunnar Hargus3,Alexandra Blak3,Oliver Cooper3,Maisam Mitalipova1,Ole Isacson3andRudolf Jaenisch1,2,,
1 The Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology, 31 Ames Street, Cambridge, MA 02139, USA
3 Udall Parkinson Disease Research Center of Excellence, Center for Neuroredegeneration Research, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA
Corresponding author
4 These authors contributed equally to this work
Summary
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.
