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Originally published in Science Express on 6 December 2007
Science 21 December 2007:
Vol. 318. no. 5858, pp. 1920 - 1923
DOI: 10.1126/science.1152092
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Reports

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,1,3 Caroline Beard,1 Tobias Brambrink,1 Li-Chen Wu,2 Tim M. Townes,2* Rudolf Jaenisch1,3*

It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell–like state by 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 anemia mouse model, we show that mice can be rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. Our results provide proof of principle for using transcription factor–induced reprogramming combined with gene and cell therapy for disease treatment in mice. The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells 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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