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Published Online July 31, 2008
Science DOI: 10.1126/science.1158799

Reports

Submitted on April 7, 2008
Accepted on July 2, 2008

Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons

John T. Dimos 1{dagger}, Kit T. Rodolfa 2{dagger}, Kathy K. Niakan 1, Laurin M. Weisenthal 1, Hiroshi Mitsumoto 3, Wendy Chung 4, Gist F. Croft 5, Genevieve Saphier 1, Rudy Leibel 6, Robin Goland 7, Hynek Wichterle 5, Christopher E. Henderson 5, Kevin Eggan 1*

1 Harvard Stem Cell Institute, Stowers Medical Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
2 Harvard Stem Cell Institute, Stowers Medical Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
3 Eleanor and Lou Gehrig MDA-ALS Research Center, Neurological Institute, Columbia University Medical Center, New York, NY 10032, USA.; Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA.
4 Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA.; Division of Molecular Genetics and Naomi Barrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
5 Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA.; Departments of Pathology, Neurology and Neuroscience, Columbia University Medical Center, New York, NY 10032, USA.
6 Division of Molecular Genetics and Naomi Barrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
7 Department of Medicine and Naomi Barrie Diabetes Center, Columbia University Medical Center, New York, NY 10032, USA.

* To whom correspondence should be addressed.
Kevin Eggan , E-mail: eggan{at}mcb.harvard.edu

{dagger}These authors contributed equally to this work.

The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell-types affected by that patient’s disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell-replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.


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