Liver Cells Converted into Pancreatic Ones

Scientific coaxing holds promise for diabetes

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By
HealthDay Reporter

FRIDAY, Jan. 31, 2003 (HealthDayNews) -- Scientists have succeeded in transforming liver cells into pancreatic cells, a feat that holds enormous promise for the 150 million people worldwide who are living with diabetes.

The research is detailed in the Jan. 21 issue of the journal Current Biology.

"This is very, very important work," says Dr. Robert Fisher, professor of surgery and director of liver transplantation and transplantation research at Virginia Commonwealth University Medical Center in Richmond. "It's a beautiful experiment and very well done."

The pancreas, which produces the hormone insulin, holds the key to curing diabetes. In healthy human beings, insulin is released after we eat to ferry glucose out of the bloodstream. People with type I diabetes produce no insulin at all and have to self-administer injections timed with their eating. People with type II diabetes, by far the most prevalent form of the disease, keep their condition under control with a combination of diet, exercise and, in some cases, medication and insulin as well.

Scientists have been experimenting for years with different ways to boost the functioning of the pancreas, including transplanting the islet cells that produce insulin. Although exciting advances have been made, no widely available therapy has yet emerged.

Here, the scientists used an approach called transdifferentiation, which involves converting one type of cell to another (in this case, liver cells to pancreatic cells).

"Other people have tried to convert cells with gene therapy, but a lot of times one single protein isn't enough. You need a combination of different factors," explains Marko Horb, lead author of the study and a postdoctoral research officer at the Centre for Regenerative Medicine at the University of Bath in England.

Horb and his colleagues basically engineered a souped-up version of a gene called Pdx1, which is necessary for fashioning the pancreas out of undifferentiated embryonic or stem cells.

The idea was to introduce the super-Pdx1 into liver cells to see if they would produce pancreatic cells.

The theory worked in two different tests, one using human cells and the other using tadpoles of the African clawed frog.

When the Pdx1 gene was added to human liver cells in the laboratory, the cells acquired characteristics of pancreas cells and some even produced insulin.

When added to tadpole liver cells, again, the Pdx1 seemed to produce all of the cell types usually found in a pancreas.

This is somewhat different from stem cell research in that the tadpole cells were in the process of differentiating into pancreatic cells, though the cells were far from mature. Other researchers were able to create, out of mouse stem cells, organs that not only produced insulin but also produced in response to the presence of glucose in the bloodstream. In other words, it functioned like a normal pancreas.

The current research leaves much to be done.

"The experiment they really need to do is take a mature animal and show that, again, they can get some transformation," Fisher says.

"They didn't do a functional study," adds Dr. Lijun Yang, assistant professor of pathology at the University of Florida College of Medicine in Gainesville. "Whether the cell can respond [to glucose] by releasing insulin is very important. In order to be useful, you have to be regulated by glucose. You don't want cells to continuously release insulin. It's exciting but the next question is can these cells really function and in response to glucose, respond to changes in the external environment."

The authors fully agree with the statements. "All we've done at this stage is to show, that with the gene we put in, a certain proportion of cells that received it became part of the pancreas," Horb says. "They produced insulin and amylase but we haven't shown they work in response. The important thing is to show they respond to glucose."

Jonathan Slack, who led the research team, believes that, if future research goes well, the method could start helping diabetics in a decade.

And the approach could have other applications. "The article is also important in understanding pancreatic cancer," Fisher says. "Some of the things they are exploring may be important in why cells become malignant."

More information

For more on islet cell transplantation, visit the Mayo Clinic or the National Diabetes Information Clearinghouse.

The American Diabetes Association has more on living with diabetes.

SOURCES: Marko Horb, Ph.D., postdoctoral research officer, Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, England; Robert Fisher, M.D., professor of surgery and director of liver transplantation and transplantation research, Virginia Commonwealth University Medical Center, Richmond; Lijun Yang, M.D., assistant professor of pathology, University of Florida College of Medicine, Gainesville; Jan. 21, 2003 Current Biology

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