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Meri Firpo

University stem cell researcher Meri Firpo says a new method of generating stand-ins for human embryonic stem cells gives a big boost to the fight against debilitating diseases.

Good news for stem cell research

Recent advances mean more weapons against intractable diseases, says U researcher Meri Firpo

By Deane Morrison

November 30, 2007

Last week, University stem cell researcher Meri Firpo heard the same news as the rest of the world: Research teams at Kyoto University, Japan, and the University of Wisconsin-Madison had separately "reprogrammed" cells taken from human skin to become what appear to be embryonic stem cells (ESC's). The advance broke a barrier to research on conditions like Huntington's disease, Alzheimer's disease, and type I diabetes. Led by Shinya Yamanaka in Japan and James Thomson in Wisconsin, the work gives Firpo and other stem cell researchers another tool to generate stem cells from large numbers of people suffering from such diseases and to study how they develop, which could well yield clues to designing cures. Firpo, who came to the University in 2005, has developed many human embryonic stem cell lines. She is based in the University's Stem Cell Institute, which has a long history of advances in stem cell biology. And while she welcomed the latest news, she was not too surprised--the surprise had come at a conference in Vancouver early in 2006, when she heard Yamanaka describe essentially the same experiment with mice. His team had inserted just four genes into ordinary adult mouse skin cells, turning them into the apparent equivalent of ESC's. "When Yamanaka spoke, jaws dropped," recalls Firpo. "We couldn't believe it was only four genes."

Behind the headlines

Last week's press attention focused on the political and clinical fallout of Yamanaka and Thomson's work. On one hand, their technology lets researchers sidestep the ethical concerns and federal funding restrictions on ESC's. But because both groups inserted genes by means that could lead to cancer or other cellular malfunctions, the method has a long way to go before it finds clinical applications. Amongst all the euphoria and caveats, the immediate implications for research were nearly drowned out. But for scientists like Firpo, who has a major interest in using stem cells to defeat type I diabetes, the new method means that research material now rare and hard to come by will soon be plentiful.

"We can reprogram [patients' skin cells as stem cells] and look at the development of the pancreas and the immune system and see if we can induce the regeneration of beta cells or prevent their destruction," says Firpo.

Suppose, for example, a researcher has private funding--federal funding is prohibited--to derive new embryonic stem cell lines from human embryos discarded by in vitro fertilization (IVF) clinics. But if the researcher wants to generate and study a line of cells from an embryo destined to develop a certain disease, finding a source is a tall order. "Many diseases, such as diabetes, have no genetic test," Firpo explains. Therefore, there's no way to identify which embryos may exhibit abnormal development that results in diabetes, Alzheimer's disease, or any number of other conditions. Even if embryos could be tested for future disease, a researcher would only be able to test the embryos that were produced by parents undergoing IVF. And for a rare disease like Huntington's, there may be few who both have the disease and choose to go through IVF, which is expensive. A lot of time and effort would be wasted in the search for cells that carry the seeds of the disease. But with the new technology, Firpo can generate stem cells from donors who already have various diseases. Then she and her colleagues can study how the tissues affected by those diseases develop, comparing them to normal cells. The goal is to find abnormalities that suggest ways to cure or control the condition. For example, in type I diabetes the patient's own immune system destroys the insulin-producing beta cells of the pancreas. It may be possible to discover how that happens by generating stem cells from patients and coaxing them to form all the cells and tissues that play roles in the disease. "We can reprogram [patients' skin cells as stem cells] and look at the development of the pancreas and the immune system and see if we can induce the regeneration of beta cells or prevent their destruction," says Firpo. "It's not easy, but now we have tools that will allow us to begin that line of research." Firpo and her colleagues are also working to improve the technology of Yamanaka and Thomson. The two research groups each reprogrammed the skin cells with four genes (two of them were identical); but the Japanese group included a known cancer gene, and both groups ferried the genes into the cells with retroviruses, which also can cause cancer or other disruptions. Furthermore, neither group could control the location in the genome where the inserted genes landed. Random insertion of new genes into chromosomes could cause resident genes to malfunction. "We will replicate the work on [the new method] to make it reversible so cells don't have permanent genetic alterations," says Firpo. While the new stem cell technology is being hailed as a brilliant solution to a thorny political problem, Firpo points out that it was only possible thanks to actual embryonic stem cells. "This would never have happened without embryonic stem cells to compare to. They'll always be the gold standard," she says. "We now have another tool for understanding reprogramming, and, if we can make [the reprogrammed cells] safe, for clinical purposes. "With both [stem cells generated by the new method] and actual embryonic stem cells,we can move forward and bring in more scientists to the field. Ultimately, we will always have to have embryonic stem cells around."