Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
American Association for Cancer Research

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

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
Prev | Table of Contents | Next

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.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells.
H. Nishikii, K. Eto, N. Tamura, K. Hattori, B. Heissig, T. Kanaji, A. Sawaguchi, S. Goto, J. Ware, and H. Nakauchi (2008)
J. Exp. Med. 205, 1917-1927
   Abstract »    Full Text »    PDF »
Get With the (Re)Program: Cardiovascular Potential of Skin-Derived Induced Pluripotent Stem Cells.
N. L. Tulloch, L. Pabon, and C. E. Murry (2008)
Circulation 118, 472-475
   Full Text »    PDF »
Generation of Functional Murine Cardiac Myocytes From Induced Pluripotent Stem Cells.
C. Mauritz, K. Schwanke, M. Reppel, S. Neef, K. Katsirntaki, L. S. Maier, F. Nguemo, S. Menke, M. Haustein, J. Hescheler, et al. (2008)
Circulation 118, 507-517
   Abstract »    Full Text »    PDF »
Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy.
M. S. Penn and A. A. Mangi (2008)
Circ. Res. 102, 1471-1482
   Abstract »    Full Text »    PDF »
Development of single mouse blastomeres into blastocysts, outgrowths and the establishment of embryonic stem cells.
C. Lorthongpanich, S.-H. Yang, K. Piotrowska-Nitsche, R. Parnpai, and A. W S Chan (2008)
Reproduction 135, 805-813
   Abstract »    Full Text »    PDF »
Androgenetic Embryonic Stem Cells Form Neural Progenitor Cells In Vivo and In Vitro.
T. C. Dinger, S. Eckardt, S. W. Choi, G. Camarero, S. Kurosaka, V. Hornich, K. J. McLaughlin, and A. M. Muller (2008)
Stem Cells 26, 1474-1483
   Abstract »    Full Text »    PDF »
Reprogrammed Mouse Fibroblasts Differentiate into Cells of the Cardiovascular and Hematopoietic Lineages.
K. Schenke-Layland, K. E. Rhodes, E. Angelis, Y. Butylkova, S. Heydarkhan-Hagvall, C. Gekas, R. Zhang, J. I. Goldhaber, H. K. Mikkola, K. Plath, et al. (2008)
Stem Cells 26, 1537-1546
   Abstract »    Full Text »    PDF »
Stem Cells and Transplant Arteriosclerosis.
Q. Xu (2008)
Circ. Res. 102, 1011-1024
   Abstract »    Full Text »    PDF »
The Management of Heart Failure: The Past, the Present, and the Future.
E. Braunwald (2008)
Circ Heart Fail 1, 58-62
   Full Text »    PDF »
Generation of isogenic pluripotent stem cells.
J. A. Byrne (2008)
Hum. Mol. Genet. 17, R37-R41
   Abstract »    Full Text »    PDF »
Seminal discoveries in regenerative medicine: contributions of the male germ line to understanding pluripotency.
N. Geijsen and D. L. Jones (2008)
Hum. Mol. Genet. 17, R16-R22
   Abstract »    Full Text »    PDF »
Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease.
M. Wernig, J.-P. Zhao, J. Pruszak, E. Hedlund, D. Fu, F. Soldner, V. Broccoli, M. Constantine-Paton, O. Isacson, and R. Jaenisch (2008)
PNAS 105, 5856-5861
   Abstract »    Full Text »    PDF »
Towards the genetic treatment of {beta}-thalassemia: new disease models, new vectors, new cells.
P. Moi and M. Sadelain (2008)
Haematologica 93, 325-330
   Full Text »    PDF »
A New Dawn for Stem-Cell Therapy.
D. R. Higgs (2008)
N. Engl. J. Med. 358, 964-966
   Full Text »    PDF »
The See-saw of Differentiation: Tipping the Chromatin Balance.
K. Muegge, S. Xi, and T. Geiman (2008)
Mol. Interv. 8, 15-18
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)