西亚试剂：Disease-corrected haematopoietic progenitors from Fanconi a

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

ángel Raya1,2,3, Ignasi Rodríguez-Pizà1, Guillermo Guenechea4,5, Rita Vassena1, Susana Navarro4,5, María José Barrero1, Antonella Consiglio1,6, Maria Castellà5,7, Paula Río4,5, Eduard Sleep1,3, Federico González1, Gustavo Tiscornia1, Elena Garreta1,3, Trond Aasen1,3, Anna Veiga1, Inder M. Verma8, Jordi Surrallés5,7, Juan Bueren4,5 & Juan Carlos Izpisúa Belmonte1,9

1 Center for Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain
2 Institució Catalana de Recerca i Estudis Avan?ats (ICREA),
3 Networking Center of Biomedical Research in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN),
4 Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 22, 28040 Madrid, Spain
5 Networking Center of Biomedical Research in Rare Diseases (CIBERER),
6 Department of Biomedical Science and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
7 Department of Genetics and Microbiology, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain
8 Laboratory of Genetics,
9 Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA

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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