Raya, A, Rodríguez-Pizà, I, Guenechea, G, Vassena, R, Navarro, S, Barrero, MJ et al.. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460: 53-59

Center for Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain.
Nature (Impact Factor: 41.46). 06/2009; 460(7251):53-9. DOI: 10.1038/nature08129
Source: PubMed


The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.

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Available from: Antonella Consiglio
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    • "Multiple studies have proved the utility of this approach (reviewed in Hanna et al., 2010; Han et al., 2011; Bellin et al., 2012; Imaizumi and Okano, 2014). Moreover, recent studies showed that mutations in patient-derived iPSCs can be corrected by genomic manipulations (Raya et al., 2009; Zou et al., 2009; Howden et al., 2011). However, many ASD-and schizophrenia-associated mutations exhibit incomplete penetrance, suggesting that genetic background effects significantly influence the clinical presentation and could contribute to the observed phenotypes. "
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    • "Because hiPSCs are developed from a patient’s own somatic cells, it is believed that hiPSCs-based therapy would be very poorly or non-immunogenic, whereas hESCs are not (125–128). The use of these cells provides an accessible, genetically tractable, and homogenous starting cell population to efficiently study human blood cell development among others (100, 103, 108, 111, 129). hESCs and hiPSCs can provide important starting cell populations to develop new cell-based therapies that have the potential to treat both malignant and non-malignant diseases. "
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    • "Efficient generation of disease-free iPSCs from FA fibroblasts corrected by gene targeting To generate disease-free FA-iPSCs, FA fibroblasts subjected to gene editing (geFA-123, geFA-52 and geFA-52T) were first enriched for EGFP + cells by cell sorting and then reprogrammed using a polycistronic excisable LV expressing the human SOX2, OCT4, KLF4, and cMYC transgenes from the EF1A promoter (STEMCCA vector; Somers et al, 2010). Consistent with previous observations (Raya et al, 2009), uncorrected FA fibroblasts did not generate iPSCs after reprogramming, even after transduction with the TERT-LV (data not shown). Although several iPSC-like colonies were generated from gene-edited FA-123 fibroblasts (115 AP + cells/100,000 fibroblasts ), no stable iPSC lines could be generated from FA fibroblasts simply subjected to gene editing, most probably because of the pro-senescence nature of these cells. "
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