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• W1569014323 abstract "DEVELOPMENTAL BIOLOGYIn a boost for scientists who hope to turn the potential of undifferentiated stem cells into medical miracles, researchers have found a way to produce insulin-producing cells from mouse embryonic stem (ES) cells.There is ready-made demand for anyone who can achieve such alchemy in human cells: millions of patients with diabetes. Doctors have reported promising results in transplanting pancreatic cells from cadavers into diabetic patients, enabling a handful of recipients to stop insulin injections indefinitely. But the demand for cells is far greater than the supply. An unlimited source of cells that can produce insulin in response to the body's cues would thus be a hot commodity.But although scientists have transformed ES cells into a range of cell types such as neurons and muscle, pancreatic beta cells—the cells that produce insulin—have been an elusive target. Scientists know relatively little about the genes that control development of the endoderm, the layer of cells in the early embryo that gives rise to many of the internal organs. Nor do they know why ES cells left to differentiate in culture spontaneously produce cells resembling muscle, neurons, and even intestine—but only rarely pancreatic cells.In a paper published online today by Science ([www.sciencexpress.org][1]), Nadya Lumelsky, Ron McKay, and their colleagues at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, describe a five-step culturing technique that can turn mouse ES cells into cell clusters that resemble pancreatic islets. The cells produce small amounts of insulin and seem to behave similarly to normal pancreas cells. “The percentage of cells that become insulin positive is remarkable and way above what others have reported,” says developmental biologist Palle Serup, who studies pancreas development at the Hagedorn Research Institute in Gentofte, Denmark.McKay's team usually focuses on brain development but was drawn to this area by recent papers showing similarities between neural and pancreatic development. For example, Serup and his colleague Ole Madsen demonstrated last year that pancreas cells and neurons use some of the same genetic pathways during differentiation. And two other teams recently reported that some pancreas cells express nestin, a protein typical of developing neural cells.![Figure][2] CREDIT: ILLUSTRATION BY C. SLAYDENThe members of McKay's team already knew how to encourage mouse ES cells to express nestin. They wondered if they could coax their nestin-positive cells to take on characteristics of pancreas cells. When they briefly exposed nestin-positive cells to a growth factor, the cells differentiated not only into neural cells but also into clusters that resemble the insulin-producing islets in the pancreas. The clusters' inner cells produced insulin, while outer cells produced glucagon and somatostatin, two proteins typical of pancreas cells. “It really looks as if you're getting bits of the animal—groups of cells that are assembled together,” McKay says. He says he and his team have grown nestin-positive cells from mouse bone marrow, but they have different properties. They have not yet tried this protocol with these adult cells.The ES-derived cells produce insulin in response to glucose—the fundamental role of beta cells—and they increase their insulin production when exposed to chemicals that prompt insulin secretion in normal pancreas cells.Important caveats remain, however. The clusters produce only about 2% as much insulin as normal islets do. And when the cells were implanted into diabetic mice, the animals' blood sugar did not return to normal, although transplanted mice survived longer than control animals. Moreover, the cells failed to produce insulin in response to a 5-millimolar concentration of glucose, a level that typically triggers a response in beta cells. “The cells are clearly not behaving as normal beta cells,” says Serup, who also notes that the gene PDX1 , a hallmark of mature beta cells, is expressed only at low levels.The low insulin production does not discourage researchers such as molecular biologist Ken Zaret of the Fox Chase Cancer Center in Philadelphia. “The glass is 1/50th full,” says Zaret, who predicts that refinements in the culture technique or drug manipulation will boost insulin production. “The amount of insulin they produce is less than it should be if they're mature beta cells,” agrees developmental biologist Douglas Melton of Harvard University. But he is nevertheless eager to see whether the technique works with human cells. McKay has shared the protocol with him, he says, and he is trying it with human ES cells in his lab. [1]: http://www.sciencexpress.org [2]: pending:yes" @default.
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• W1569014323 date "2001-04-27" @default.
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• W1569014323 title "Stem Cells Are Coaxed to Produce Insulin" @default.
• W1569014323 doi "https://doi.org/10.1126/science.292.5517.615b" @default.
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