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Retracing Stem Cell Development Leads to Insulin-Producing Cells

beta cells



E. E. BAETGE, Novocell
Mimicking the series of steps by which an embryo develops has led to a significantly more efficient way of creating insulin-secreting cells. A team of researchers reports that by applying a sequence of chemicals to human embryonic stem cells in a culture dish, it has grown layers of cells similar to pancreatic tissue in a young embryo. Such cells may eventually be suitable for treating diabetes.

Embryonic stem cells are a gold mine for medical research because they could potentially replace nearly any type of failed or damaged tissue. In a prime example, research groups have shown that embryonic stem cells can morph into the pancreatic cells that produce insulin, called beta cells. In people with diabetes these cells have stopped working properly. Prior instances of the transformation were sporadic and inefficient, though, appearing in cells transplanted into animals or in embryolike jumbles of cells, says Emmanuel Baetge, chief scientific officer at Novocell, a San Diego biotech company. The key to making pancreatic cells at will, Baetge says, is going to the source--so-called definitive endoderm, the layer of embryonic tissue that gives rise to all the organs of the gut, including the pancreas. "You cannot make pancreatic cells without it," he says.

Novocell researchers had already published a method for growing endoderm from cultured embryonic stem cells by applying a chemical that is known to stimulate endodermal development in growing embryos. In a paper published online October 19 in Nature Biotechnology, the group describes taking the next steps: They added four more sets of growth factors to the endoderm they had created, still following the pathway deciphered in growing embryos. An average of 7 percent of the resulting cells produced all five pancreatic hormones, including insulin, and contained nearly as much insulin as adult beta cells, the researchers report. "What we've really done is taken developmental biology and applied it to stem cell biology," says Baetge. "These cells really can do it; you just have to have to understand how to work with them."

The cells are still immature, however. So unlike adult cells, they do not make insulin in response to glucose, and they would need further prodding to reach the mature state. Nevertheless, "a lot of people are excited about this paper," says beta cell biologist Ole Madsen of the Hagedorn Research Institute in Gentofte, Denmark. "The big novelty is that everything is controlled. It's sort of a defined procedure." Novocell's method for making endoderm has been reproduced in other labs, Madsen notes. Assuming the same holds for the new work, he says, "it has given people hope for much quicker progress than was anticipated."

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