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“They show that they can make the cells young,” says Lorenz Studer, a physician and scientist at Memorial Sloan-Kettering Cancer Center, in New York, who was not involved in the research. The defect in the telomerase enzyme “seems to be repressed or overridden during reprogramming, which probably explains why patients do reasonably well in the early stages of life,” he says. “Patients still have same mutation whether in the [skin cell] or iPS cell, but the mutation only manifests itself in the differentiated cell.”

The researchers found that reprogramming appeared to activate a specific component of the telomerase enzyme, a discovery that they hope to use to develop new treatments for this and other telomerase-related diseases. Agarwal hopes to search for drugs that boost the enzyme.

“This disease is an ideal case for the clinical application of telomere-rejuvenated adult stem cells or iPS cell therapies, because the primary defect of telomerase deficiency does not need to be corrected if telomerase function can be temporarily stimulated enough to elongate telomeres,” wrote Kathleen Collins, a biologist at the University of California, Berkeley, in an e-mail. “This work shows that the iPS state does exactly that.”

The findings are an early example of the potential of induced pluripotent cell reprogramming, a technology first developed in 2007 as a tool for studying human disease. The technique, in which genetic engineering or chemicals are used to activate genes normally expressed in embryonic cells, allows scientists to create stem cells from patients with different diseases. The hope is that differentiating these cells into the cell type affected by the disease will allow researchers to study the molecular mechanisms that cause it.

Studer points out that the new research could shed light on how the age or telomere status of a cell might affect how it manifests a particular disease. For example, it’s not yet clear whether cells derived from patients with an age-related disease, such as Parkinson’s or Alzheimer’s, will show signs of the disease soon after reprogramming, or if the cells must age–cycling through a number of cell divisions–to more accurately reflect age-related ailments.

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Credit: Suneet Agarwal

Tagged: Biomedicine, stem cells, iPS cells, reprogramming

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