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Submitted on October 23, 2007
Accepted on November 26, 2007
Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin
Jacob Hanna 1,Marius Wernig 1,Styliani Markoulaki 1,Chiao-Wang Sun 2,Alexander Meissner 1,John P. Cassady 3,Caroline Beard 1,Tobias Brambrink 1,Li-Chen Wu 2,Tim M. Townes 4*,Rudolf Jaenisch 3*
1 The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. 2 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Schools of Medicine and Dentistry, Birmingham, AL 35294, USA. 3 The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.; MIT Department of Biology, Cambridge, MA 02142, USA. 4 MIT Department of Biology, Cambridge, MA 02142, USA.
* To whom correspondence should be addressed.
Tim M. Townes , E-mail: ttownes{at}uab.edu Rudolf Jaenisch , E-mail: Jaenisch{at}wi.mit.edu
It has recently been demonstrated that mouse and human fibroblastscan be reprogrammed into an embryonic stem cell–like stateby introducing combinations of four transcription factors. However,the therapeutic potential of such induced pluripotent stem (iPS)cells remained undefined. By using a humanized sickle cell anemiamouse model, we show that mice can be rescued after transplantationwith hematopoietic progenitors obtained in vitro from autologousiPS cells. This was achieved after correction of the human sicklehemoglobin allele by gene-specific targeting. Our results provideproof of principle for using transcription factor–inducedreprogramming combined with gene and cell therapy for diseasetreatment in mice. The problems associated with using retrovirusesand oncogenes for reprogramming need to be resolved before iPScells can be considered for human therapy.
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