Disease-corrected haematopoietic progenitors from Fanconi anemia induced pluripotent stem cells

Abstract

The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and/nprovided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great/ntherapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect,/nsomatic 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.