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ES cell model could provide clues to causes, cures for diabetes

cursor cells and islet cells producing four types of hormones, including insulin and glucagon.

But the study goes beyond confirming the ability of embryonic stem cells to form cells critical to regulating the body's blood sugar. The researchers say it offers a much-needed model for studying normal pancreatic development.

"In the process of identifying differentiated cell types, we carefully characterized the stages of their development," says Odorico. "These stages appear to recapitulate many aspects of normal development." In other words, islet and pancreatic precursor cells that were differentiated from embryonic stem cells in vitro, or outside the body, developed in ways similar to those differentiated in vivo, or inside the body.

For example, the cultured cells, just like those in the body, began to show features of early embryonic pancreas cells, such as the expression of specialized early transcription factors important for the formation of the pancreas. They also showed similar patterns of islet hormones, expressed genes that help regulate islet cells and ultimately generated insulin-producing cells.

"If human embryonic stem cells can be shown to differentiate to islets in this way with this culture system, then we can use this system to compare mouse and human pancreas developmental pathways for the first time," explains Odorico. Because access to fetal pancreatic material is limited, he adds, "most of what we think we know about human pancreatic development is merely extrapolated from mouse studies."

This model based on mouse embryonic stem cells that identifies their differentiation into pancreatic precursor cells and islet cell types, says Odorico, "should provide a valuable tool to study normal islet and pancreatic development. One could potentially use this model to identify novel genes and learn how islets form."

From all this, he adds, researchers could gain better insight into the causes of pancreas-
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Contact: Jon Odorico
jon@tx.surgery.wisc.edu
608-265-6471
University of Wisconsin-Madison
28-Jul-2003


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