Liver
Cells Converted into Pancreatic Ones
Scientific
coaxing holds promise for diabetes
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 a recent 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."
Pancreas
Holds the Key to Curing Diabetes
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 1 diabetes
produce no insulin at all and have to self-administer injections timed
with their eating. People with type 2 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.
The
Transdifferentiation Approach
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 determine 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.
Additional
Research Is Necessary
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 persons with diabetes 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."
Always
consult your physician for more information.
Online
Resources
American
Diabetes Association
American
Heart Association
Centers
for Disease Control and Prevention (CDC)
Current
Biology
Diabetes
Care
Journal
of Nutrition
National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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