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Reprogrammed: Scientists have genetically modified skin cells so that they behave like embryonic stem cells, which can develop into virtually every tissue type in the body.

On the second floor of a building in one of South San Francisco’s numerous business parks, a new biotech company has set up shop. The walls sport a fresh coat of white paint, and the bench tops are shiny and bare. The tile floors are still glossy, and an expensive new cell-sorting machine sits, untouched, on the loading dock downstairs.

The building’s new inhabitant, iZumi Bio, is pursuing a technology as new and full of promise as the lab itself–a technology that’s moving faster than the company can fill its empty space. It revolves around induced pluripotent stem (iPS) cells: adult cells genetically reprogrammed to act like embryonic stem cells, which can turn into just about any type of cell in the human body.

Scientists have been talking about the medical promise of stem cells for more than a decade, even before human embryonic stem cells were successfully isolated in 1998. Most of the public attention has focused on their regenerative power: since stem cells can renew themselves and differentiate into specialized cell types, they could potentially be used to build replacement organs, heal spinal-cord injuries, or repair damaged brain tissue. But the research world has also pursued another, even broader-reaching goal: using the cells of patients with various illnesses to derive pluripotent stem cells, which can give rise not just to the specialized cells in a particular organ or tissue but to virtually any cell type. Those cells could be used to create laboratory models of disease. For example, a cell from a Parkinson’s patient could be turned into a neuron, which would exhibit the progressive molecular changes at work in the neurodegenerative disorder. This type of tool could capture the details of human disease with unprecedented accuracy, and it could revolutionize the way researchers search for new treatments.

Studying human disease in the lab is an enormously challenging task. It’s difficult to obtain brain tissue from a living Alzheimer’s patient, for example, and impossible to study how that tissue changes as the disease progresses. Animal models can offer only rough approximations of a human illness, capturing at best a few of its symptoms or causes. But iPS cells could yield a much more comprehensive picture. Because each cell line comes from a human patient, the cells reflect the complex array of factors that led to the patient’s disease: the genetic mutations, the effects of environmental history. And because those cells can be prodded to develop into a variety of tissue types, scientists can watch the disease unfold in a petri dish. They can observe, for example, the subtle molecular changes that take place in the neurons of a patient with Alzheimer’s long before the telltale signs of the disease, such as amyloid plaques, can be seen in the brain. It’s the difference between trying to piece together the details of a plane crash from photos of the wreckage and watching a video of the crash from every angle, with the ability to stop, zoom in, and rewind at will.

“The past two years have been nothing short of a revolution,” says John Dimos, a senior scientist at iZumi. “These cells didn’t really exist two years ago. This is all brand-new technology, and it’s opening up the potential for brand-new science.” The company plans to take advantage of that potential by developing a bank of iPS cells from patients with various diseases and using the cells to screen candidates for drug development.

Thousands of other labs are jumping at the chance to use iPS cells as well–whether to create new disease models, to study tissue development, or even to figure out how to build tissue for transplantation. Biologists say the field is charged with a kind of energy not seen since soon after the structure of DNA was discovered. “This is a really rare phenomenon in the biological research community,” says Sheng Ding, a chemist at the Scripps Research Institute in La Jolla, CA. “It’s a sensation, really. Everyone, more or less, is working on using iPS-cell technology for their specific research interest.”

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Credits: Junying Yu/University of Wisconsin-Madison, Technology Review

Tagged: Biomedicine, stem cells, diseases, embryonic stem cells, stem cell therapy

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