Researchers transform pancreas cells into insulin-producing cells

NBC Nightly News (8/27, story 9, 0:30, Williams) reported that "biologists at Harvard [University] say they’ve transformed one type of fully developed adult cell into another type."
On its front page, the Washington Post (8/28, A1, Stein) reports that in a study published online in the journal Nature, Douglas A. Melton, of the Harvard Stem Cell Institute, and colleagues, used a process called “direct reprogramming” to transform ordinary pancreas cells into cells that produce insulin, “a startling advance that could lead to cures for a variety of illnesses and sidestep the political and ethical quagmires associated with embryonic stem cell research.” Mice experiments allowed esearchers to pinpoint “three crucial molecular switches that, when flipped, completely” reprogrammed the cells. This finding raises "the prospect that patients suffering from not only diabetes but also heart disease, strokes, and many other ailments could eventually have some of their cells reprogrammed to cure their afflictions without the need for drugs, transplants, or other therapies."
For their study, the researchers “identified nine key genes that are active in mature beta cells and their close relatives,” the Los Angeles Times (8/28, Kaplan) adds. "Then they started turning them on and off in every possible combination to determine which were necessary to make insulin-producing cells. They ultimately determined that only three were essential to the process, and they were activated by the proteins Ngn3, Pdx1, and Mafa."
The researchers then “infected the pancreases of dozens of two-month-old mice with a virus that contained three genes active in insulin-producing beta cells,” USA Today (8/28, Vergano) notes. “More than 20 percent of the infected pancreas cells turned into beta cells, a rate hundreds of times better than past attempts to turn embryonic stem cells into such specialized tissues.” The transformed “cells made the beta cell switch in only three days” because they did not first divide “into less-specialized embryo-like tissues, which take weeks to develop into specific organ tissues.”
“Besides producing insulin, the transformed exocrine cells looked like beta cells and ceased making proteins typical of exocrine cells,” the New York Times (8/28, A20, Wade) explains. But, the reprogrammed cells "did not organize themselves into the pancreatic structures known as islets where beta cells usually cluster."
The AP (8/28, Ritter) points out that the cells also "didn’t fully replenish the insulin supply, but maybe there were too few of them, or they were hampered by not forming clusters like ordinary beta cells do, researchers said."
Similarly, Carolyn Y. Johnson wrote in the Boston Globe’s (8/27) White Coat Notes blog that "the researchers did not cure diabetes in a mouse model."
The Financial Times (8/28, Cookson) reports, however, that the cells did “produce insulin for the lifetime of the mice, reducing diabetes symptoms in the animals.” Still, obstacles lie ahead. Researchers must "find a way to reprogram human cells with safe chemicals rather than the virus used to carry transcription factors into the laboratory mice."
Instead of using viruses, the researchers “will be exploring two different strategies for using the technique as a treatment,” according to Bloomberg (8/28, Waters). The first method “would involve directly injecting the genes into a human pancreas.” In the second method, researchers "would take exocrine cells from the cadavers of organ donors, convert them in the laboratory to beta cells, coax them to congregate into clusters known as islets, and transplant those into patients. This may be the safest way to proceed, Melton said."
Although Melton theorized in a Milwaukee Journal Sentinel (8/27, Fauber) report that direct reprogramming “might be used to treat both Type 1 diabetes and insulin-dependent Type 2 diabetes,” his team was unable to stop “the immune attack that kills beta cells” in Type 1 diabetes. It is also unclear whether this “approach [will] work in the brain and the heart.” Melton’s team is not sure whether the process “will be able to produce enough cells.” As a result, “embryonic stem cells still will be needed, said Timothy Kamp,” of the University of Wisconsin.
MedPage Today (8/27, Gever) echoed that sentiment, noting that “Melton emphasized that research on stem cells would continue to be important and would remain a major focus of the Harvard institute.” He said that direct reprogramming "‘could be a kind of parallel approach for how to make cells for regenerative medicine,’ alongside the use of embryonic or artificially induced pluripotent stem cells."
AHN (8/28, Sharma), Wired’s (8/27, Keim) Science blog, the U.K.'s Daily Mail (8/28, Derbyshire), the U.K.'s Press Association (8/28), and the UPI (8/28) also cover the story.

Endocrine Daily Briefing