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Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin
Jacob Hanna,1Marius Wernig,1Styliani Markoulaki,1Chiao-Wang Sun,2Alexander Meissner,1John P. Cassady,1,3Caroline Beard,1Tobias Brambrink,1Li-Chen Wu,2Tim M. Townes,2*Rudolf Jaenisch1,3*
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.
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 Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02142, USA.
* To whom correspondence should be addressed. E-mail: Jaenisch{at}wi.mit.edu (R.J.); ttownes{at}uab.edu (T.M.T.)
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