@article{036a15ea2be4487d9ed240a0730f3cc6,
title = "Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors",
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.",
keywords = "DEVBIO, HUMDISEASE, STEMCELL",
author = "Frank Soldner and Dirk Hockemeyer and Caroline Beard and Qing Gao and Bell, {George W.} and Cook, {Elizabeth G.} and Gunnar Hargus and Alexandra Blak and Oliver Cooper and Maisam Mitalipova and Ole Isacson and Rudolf Jaenisch",
note = "Funding Information: We thank Tobias Brambrink for providing the FUGW-loxP plasmid. We thank Raaji Alagappan, Ping Xu, Kristen Lee, and Elizabeth Marlow for technical support and Jessica Daussman, Ruth Flannery, and Dongdong Fu for their help with animal husbandry and processing of teratomas. We would like to thank the members of the Whitehead Genome Technology Core for their help with the microarray expression analysis. We thank all the members of the Jaenisch lab for helpful discussions and comments on the manuscript. D.H. is a Merck Fellow of the Life Science Research Foundation. R.J. was supported by NIH grants R37-CA084198, RO1-CA087869, and RO1-HD045022. This research was supported in part by a Collaborative Innovation Award from the Howard Hughes Medical Institute. O.I. is supported by Udall Parkinson's Disease Center of Excellence grant P50NS39793 and the Michael Stern Foundation. R.J. is an advisor to Stemgent, which has obtained a license from the Massachusetts Institute of Technology (MIT) to distribute some of the reagents used in this paper. F.S., D.H., and R.J. designed the experiments and wrote the paper. C.B. designed and performed Southern blot analysis. Q.G. analyzed all teratomas. G.B. analyzed the gene expression profile. E.G.C. assisted with the methylation analysis. G.H., A.B., O.C., and O.I. performed and analyzed differentiation experiments of Figure 3 B, and C. M.M. provided human ES cell controls. F.S. and D.H. performed all other experiments. ",
year = "2009",
month = mar,
day = "6",
doi = "10.1016/j.cell.2009.02.013",
language = "English (US)",
volume = "136",
pages = "964--977",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}
