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

By F. Soldner, D. Hockemeyer, C. Beard, Qing Gao, George W. Bell, Elizabeth G. Cook, G. Hargus, A. Blak, O. Cooper, M. Mitalipova and 2 more. Cell, 2009

1,590 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/36e2c7d730594e90edf31bb8a8596011406b9ff7

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Citations in the corpus

Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations (2011, positive): “reprogramming (Soldner et al., 2009) and genetic alterations introduced during the reprogramming process (Gore et al.”
Floor plate-derived dopamine neurons from hESCs efficiently engraft in animal models of PD (2011, methodology): “Patterning of neural rosettes represents the currently most widely used strategy for deriving DA neurons from PSC”
Somatic cell reprogramming and transitions between pluripotent states: facts, hypotheses, unresolved issues (2010, positive): “, 2010) represent ‘‘epigenetic memory’’ or simply result from residual transgene induction levels that are specific to the cell of origin and that induce perturbations in gene expression (Soldner et al., 2009), which may subside with silencing of the transgenes upon extended cell passaging.”
Immune Influence on Adult Neural Stem Cell Regulation and Function (2009, positive): “iPSC lines have been created from patients with neurological diseases such as PD, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) (Dimos et al., 2008; Ebert et al., 2009; Soldner et al., 2009).”
Induced pluripotency: history, mechanisms, and applications. (2010, background): “Lentiviral vectors are also more efficient than retroviral vectors at infecting different somatic cell types and can be used to express polycistronic cassettes encoding all four reprogramming factors, thus increasing reprogramming efficiency (Carey et al. 2009; Sommer et al. 2009).”
Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines (2011, positive): “For example, it will be interesting to measure whether the use of integration-free methods for reprogramming (Soldner et al., 2009; Warren et al., 2010) has an effect on the differentiation propensities of iPS cell lines.”