Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors

Frank Soldner, Dirk Hockemeyer, Caroline Beard, Qing Gao, George W. Bell, Elizabeth G. Cook, Gunnar Hargus, Alexandra Blak, Oliver Cooper, Maisam Mitalipova, Ole Isacson, Rudolf Jaenisch

Research output: Contribution to journalArticle

1152 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)964-977
Number of pages14
JournalCell
Volume136
Issue number5
DOIs
StatePublished - Mar 6 2009
Externally publishedYes

Keywords

  • DEVBIO
  • HUMDISEASE
  • STEMCELL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G. W., Cook, E. G., Hargus, G., Blak, A., Cooper, O., Mitalipova, M., Isacson, O., & Jaenisch, R. (2009). Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors. Cell, 136(5), 964-977. https://doi.org/10.1016/j.cell.2009.02.013