Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors
Author(s)Soldner, Frank; Hockemeyer, Dirk; Beard, Caroline; Gao, Qing; Bell, George W.; Cook, Elizabeth G.; Hargus, Gunnar; Blak, Alexandra; Cooper, Oliver; Mitalipova, Maisam; Isacson, Ole; Jaenisch, Rudolf; ... Show more Show less
MetadataShow full item record
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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
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.
Final published version