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Stem cells derived from the skin of an 82-year-old patient with amyotrophic lateral sclerosis (ALS) could provide a novel model for studying the degenerative motor disease and for screening new treatment drugs; eventually, it could pave the way for cell-replacement therapies. The findings, published today online in Science, were made possible by new techniques to reprogram adult cells to become pluripotent–able to become any type of cell in the body.

Researchers have long wanted to make stem cells from actual patients to better understand the diseases from which they suffer. “Because the cells harbor genes that led to the disease in that patient, we might be able to use them in the laboratory to understand certain aspects of disease,” says Kevin Eggan, a stem-cell scientist at the Harvard Stem Cell Institute, who led part of the research.

To create the stem cells, researchers used a novel technique, recently developed by scientists in Japan, that doesn’t require human eggs or the creation or destruction of embryos, and thus bypasses major ethical and technical hurdles that have plagued the field of embryonic stem-cell research. Eggan’s team exposed the patient’s skin cells to four genetic factors found in the developing embryo. The procedure turned back the clock on the cells, triggering them to look and behave like embryonic stem cells.

While scientists had already used these reprogramming techniques to create stem cells from skin cells, this is the first time that these cells–called induced pluripotent stem cells, or IPS cells–have been generated from a patient. The ability to do so is key to creating models for studying complex genetic diseases, such as Alzheimer’s. The findings also confirm that it’s possible to use reprogramming techniques in older people and in those with a serious disease. “It was unclear if the fact that the patient had been sick for many years would interfere with our ability to reprogram [the cells],” says Eggan.

The researchers prodded the stem cells to differentiate into motor neurons by exposing them to another series of chemicals. Motor neurons are the primary cell type destroyed in ALS, a progressive neurodegenerative disease. While animal models of the disease exist, they can’t capture the complexity of human biology.

The new research allows scientists to generate an endless supply of motor neurons that are genetically identical to those of the cell donor, which should allow them to study the molecular events that trigger the disease. “Now we can see if they behave in a manner that mimics the disease,” says Chris Henderson, codirector of the Motor Neuron Center at Columbia University, in New York, who led part of the research. “For example, do they tend to die and degenerate in the culture dish? If so, we can try to understand more about the mechanism of degeneration.” Scientists also hope to use the cells to screen for new drugs that protect against neurodegeneration in ALS.

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Credits: Kit Rodolfa and John Dimos at Harvard University

Tagged: Biomedicine, stem cells, diseases, reprogramming, ALS, degenerative diseases

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