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.
Bibliographical noteFunding Information:
Acknowledgements The authors are indebted to FA patients and their families for their cooperation. We are grateful to I. Badell, J. Couselo, A. Almeida and D. Schindler for collaboration in providing samples from FA patients, J.A. Casado for subtyping studies, M. Edel, J. Bilic, V. Pekarik and members of the laboratory for comments on the manuscript, J. M. Andrés-Vaquero for assistance with flow cytometry, R. Pujol for assistance with cytogenetics, M. J. Ramirez for immunofluorescence studies, B. Arán, M. Carrió and Y. Muñoz for assistance with cell culture techniques, E. Melo, L. Mulero and M. Martífor bioimaging assistance, and Y. Richaud, T. Lopez Rovira and M. L. Lozano for technical assistance. I.R.-P. and E.S. were recipients of pre-doctoral fellowships from MEC and DIUE, respectively. M.J.B. and G.T. were partially supported by the Ramón y Cajal program, and J.S. by the ICREA-Academia program. This work was partially supported by the Ministerio de Educación y Ciencia grants BFU2006-12251, SAF2005-00058, SAF2006-3440, and Genoma España (FANCOGENE), European Commission ‘Marie-Curie Reintegration Grant’ MIRG-CT-2007-046523 and European Program CONSERT LSHB-CT-2004-5242, the Fondo de Investigaciones Sanitarias (RETIC-RD06/ 0010/0016, PI061897, PI061099), Marató de TV3 (063430), the G. Harold and Leila Y. Mathers Charitable Foundation, Fundación Marcelino Botín, and Fundación Cellex.
ASJC Scopus subject areas