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[IPp] Scientists Generate Human Islet Precursor Cells In Culture

Generate Human Islet Precursor Cells In Culture
 Scientists at the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), one of the National Institutes of Health (NIH), have induced
human insulin-producing cells of the pancreas to revert to islet precursor
cells. These precursor cells are capable of expansion and appear to naturally
and efficiently differentiate into clusters of islet-like cells. This work may
help to clarify the natural lifecycle of the beta cell and may eventually have
applications for diabetes treatment. The study appears on-line today in Science
Express, the rapid publication web site of the journal Science.


 Insulin-producing beta cells exist in spherical clusters, called islets, in the
pancreas. Research shows that beta cells are born, die, and are replaced by
other beta cells throughout a person's lifetime, but little is known about the
process. When the body cannot produce or replace beta cells, insulin levels fall
causing blood glucose levels to rise and diabetes results. This study's findings
may eventually have implications for islet transplantation, an experimental
treatment for type 1 diabetes.

 "This is a step forward in the field, but we're still a long way from using
this knowledge to develop a therapy for diabetes," says lead author, Marvin C.
Gershengorn, M.D., Scientific Director of NIDDK's Division of Intramural
Research and Chief of the institute's Clinical Endocrinology Branch. "For one
thing these differentiated cells do not function as well as the original cells.
They don't produce as much insulin and they are not as adaptable to changes in
the environment. For another thing, we grew these cells in a culture that is not
optimal for use in humans, so we are not ready to transplant these cells into
people. Still, I am encouraged."

 The researchers removed islets from human cadaver pancreata, as is done before
islet transplantation, and exposed these islets to a medium containing fetal
bovine serum. Over 17 days the cells in the clusters migrated out until the
original islets were depleted. These migrating islet cells, identified as
insulin-expressing cells, then transformed into more primitive precursor cells
that do not produce insulin.

 These new cells, called human islet-derived precursor cells (hIPCs), reproduce
easily. The researchers observed that the hIPCs showed substantial proliferative
potential, doubling in number about every 60 hours, and by 90 days had expanded
by almost a billion fold. Not stem cells, these precursor cells are transitional
cells since they originated from insulin-producing islets. The authors note,
however, that this finding does not preclude the possible existence of islet
stem cells, as yet undiscovered.

 "We knew that islets regenerate," says Gershengorn. "When old islets die out,
the pancreas produces new ones to take their place. So, we thought, there must
be cells within the pancreas that can reproduce and efficiently differentiate
into hormone-producing cells or even intact islets. The challenge was to
identify them and make them work."

 After isolating significant numbers of hIPCs and showing that they are highly
proliferative, the researchers wanted to see if they could reverse the process
and induce the new cells to become insulin-producing again. In the second stage
of their study, the researchers exposed cultures of hIPCs to a serum-free
medium. They saw a highly efficient, gradual transition from precursor hIPCs to
epithelial islet-like cell aggregates over a period of several weeks. The cell
aggregates produced insulin and other hormones, but at much lower levels than
that of human islets  about 0.02 percent of the level of insulin produced by
healthy islets. Still, the islet-like cells did show many of the characteristics
of the original beta cells. "It appears, therefore, that hIPCs are
pre-determined to transition back into hormone-producing cells under minimal
conditions in culture," added Gershengorn.

 One of NIDDK's goals for long-term diabetes research is to better understand
the beta cell and how it regenerates. These findings may eventually have
implications for diabetes treatments, including islet transplantation. Islet
transplantation involves the infusion of islets derived from donor pancreata
into a person with complicated type 1 diabetes. The hope is that some of the
transplanted cells will survive in the pancreas and continue producing insulin.
A major obstacle to the wider use of islet transplantation as a treatment for
type 1 diabetes is the small number of donor pancreata that become available for
use each year and the large number of islets needed for transplantation. The
NIDDK is focusing its research on understanding the beta cell and its
regeneration and on efforts to develop alternative sources of beta cells.

 The researchers hope that future studies will corroborate their findings and
address some of the unanswered questions. For example, the researchers plan to
conduct studies to try to define the optimal environmental conditions to grow
precursor cells and to stimulate them to differentiate into hormone-producing
cells. Their goal is to design a cellular environment as close as possible to
the natural environment of a healthy human pancreas. Another challenge is to
develop a culture medium that does not rely on animal serum, so cells grown in
the lab can be transplanted back into people with a minimum risk of side


 More information on islet transplantation can be found on the NIDDK web site:

Editor's Note: The original news release can be found here.

Rachel - email @ redacted
"Foolproof systems don't take into account the ingenuity of fools." 

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