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The relative simplicity of the approach–and the fact that it can be supported by federal funding–means that many more scientists are likely to attempt reprogramming than cloning. (In 2001, President Bush limited federal funding for embryonic stem-cell research to embryonic stem-cell lines already in existence.) According to Story Landis, chair of the Stem Cell Task Force at the National Institutes of Health, in Bethesda, MD, the funding agency has already announced two programs to fund reprogramming research and would welcome applications to derive cell lines from patients.

While no one has yet announced that he or she has derived a disease-specific cell model, George Daley’s lab at Harvard may be in the lead. Last month, he and his team published a paper in Nature showing that they can reprogram cells from a skin biopsy from a healthy person, and they are already trying to repeat the feat with tissue from patients. Ultimately, they are interested in developing models of sickle-cell anemia and Fanconi anemia, a hereditary disease in which the bone marrow doesn’t produce enough new cells to replenish the blood.

For example, patients with Fanconi anemia often suffer from skeletal problems, and their cells show an impaired ability to repair DNA. “We don’t have any idea why kids with DNA repair defect would get a blood disease, and why they sometimes get these bone abnormalities,” says Lensch, who works with Daley. But with stem-cell lines developed from a patient, “we could push the cells to develop into bone and blood, and try to learn about the links between the two.”

Such models could also help resolve long-held debates about specific diseases, such as Alzheimer’s. By differentiating reprogrammed cells from Alzheimer’s patients into neurons and comparing them with neurons derived from healthy embryonic stem cells or with cells with mutations that mimic a rare, hereditary form of the disease, scientists will be able to determine how much of Alzheimer’s is due to the environment versus genes, as well as how similar the sporadic form of the disease is to the hereditary form. (Most drugs on the market for Alzheimer’s were developed using models that mimic the hereditary form of the disease and have shown limited efficacy in patients.) “This is a whole new world of investigation,” says Lawrence Goldstein, a neuroscientist at the University of California, San Diego, whose lab is about to begin collecting skin cells from Alzheimer’s patients.

Despite the excitement, Lensch and others caution against abandoning other embryonic stem-cell research, especially therapeutic cloning. “We’re in the early stages of this research, where we’re excited about the possibilities but still need to show it’s both useful and representative of the disease,” says Snyder. In addition, he says, embryonic stem cells and perhaps cloned stem cells will be needed as controls for future studies.

Scientists also say that it’s too soon to tell how easy it will be to generate stem-cell lines from patients: the genetic variations that lead to the disease could also impact the reprogramming process. “With some genetic disease, I think it will be really difficult,” says Lensch.

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Credit: Jon Chase/Harvard News Office

Tagged: Biomedicine, stem cells, Alzheimer’s

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