Hurt an Organ, Help a Disease?
By Jennifer Couzin
ScienceNOW Daily News
24 January 2008
Researchers report that by injuring an animal's pancreas, they have
found a population of cells that naturally become insulin-producers.
It's not clear whether the find will impact diabetes patients, but
researchers are intrigued by the discovery and what it might reveal
about the transformative ability of pancreatic cells.
In people with diabetes, insulin-producing cells in the pancreas,
called beta cells, have been destroyed or may behave sluggishly. This
leaves the body unable to regulate its blood sugar. Coaxing the
pancreas to make new beta cells is one of the great goals of diabetes
research. Scientists debated for years whether the pancreas holds
stem cells that could replenish beta cells, but in 2004, biologists
led by Douglas Melton at Harvard looked for these stem cells in the
pancreas of mice and failed to find them. His team instead reported
that existing beta cells could multiply to form new ones (ScienceNOW,
5 May 2004).
Harry Heimberg of Vrije Universiteit in Brussels, Belgium, wondered
whether there were additional sources of new beta cells. Earlier
experiments in rats had found that clamping a pancreatic duct and
stopping digestive enzymes from entering the small intestine roughly
doubles the mass of beta cells in the pancreas. But which cells in
the pancreas were generating these extra beta cells?
Heimberg and his colleagues caused the same severe injury in mice.
Then they searched for pancreatic cells that might somehow turn into
beta cells. To do this, they focused on the genetic marker neurogenin
3, which appears in cells slated to become beta cells when they're
just beginning to develop in an embryo. Within 3 days of injury, the
scientists found cells with this gene. Furthermore, preventing the
gene's expression reduced beta-cell proliferation, the group reports
in the 25 January issue of Cell. When these neurogenin 3 cells were
taken from an adult mouse and injected into a pancreas removed from a
mouse embryo, they developed into beta cells and produced insulin,
suggesting that the cells were developing into new beta cells in the
injured animal. Further studies found that the neurogenin 3 cells
weren't making insulin before the injury. That means beta cells
hadn't bolstered the beta-cell supply by themselves, as Melton had
shown was possible in normal animals.
Many questions remain. Where do the cells come from, for example? The
cells sit along the ducts of the organ, so they could originate as
mature ductal cells that revert to an embryonic state after the
injury and then become beta cells. Or, says Heimberg, they could be
progenitor cells, which unlike stem cells cannot self-replenish.
Other big questions are whether the neurogenin 3 cells can be coaxed
to come forward in the normal human pancreas without damaging the
organ, and whether they can be turned into insulin producers.
Melton suspects the cells began as mature pancreatic cells, likely
from the ducts, as they don't have many characteristics of stem
cells. The study, he says, shows that there's another mechanism to
keep beta cells coming, which might offer a new cell source to
consider in the hunt for ways to replenish beta cells.
http://sciencenow.
Elusive Pancreas-Healing Cells Discovered
Mouse finding hints that stemlike cells may yet be found in human
pancreas
By JR Minkel
PROGENITOR POWER: Injections of newly discovered mouse pancreatic
cells (green) into an embryonic mouse pancreas engineered to function
improperly restored its hormone-secreting ability.
Courtesy of Harry Heimberg and Xiaobo Xu
Don't call them stem cells just yet, but researchers say they have
discovered a rare and long-sought class of cell in adult mice that is
responsible for patching up an injured pancreas. If equivalent cells
were found in the human pancreas, the hope is that they would point
the way to therapies for growing new insulin-secreting beta islet
cells, which cause diabetes when they break down.
"That's the far away dream, but the data we find in mice gives us the
hope this kind of reasoning makes sense," says biologist Harry
Heimberg of Vrije University Brussels in Belgium, who the led the
research, published in the journal Cell.
Unlike stem cells, the newly discovered cells, referred to as
progenitors, do not reproduce repeatedly in the lab. But according to
the study, they are capable of differentiating into all cell types of
the islets of Langerhans, pancreatic structures that include beta
cells and cells that secrete hormones such as glucagon and
somatostatin. Heimberg and his co-workers first injured the islets of
adult mice by clamping shut the ducts that carry digestive enzymes
out of the pancreas, causing a destructive backup.
The injured pancreases, forced to repair themselves, soon swelled
with double the normal number of beta cells. The researchers note
that the only previously known source of new beta cells in adult mice
was the slow cell division of preexisting beta cells. Seeking fresh
sources, they looked for cells that express the gene neurogenin 3, a
potential sign of cell differentiation because it is the first gene
to only switch on in pancreatic islets during embryonic development.
The team found an estimated 5,000 such cells, some of which were
isolated and tested for their ability to restore beta cell activity.
The researchers did this by injecting the cells into embryonic
pancreatic tissue taken from mice engineered to lack neurogenin 3.
The embryonic pancreas was incapable of secreting insulin and other
hormones by itself. But the extracted tissue began producing insulin,
glucagon and other hormones after the newly identified cells were
added, indicating that they were indeed progenitors capable of
differentiating into all the islet cell types, including beta cells.
The source of these progenitors, however, remains a mystery. "It's
necessary now to look for the precursors of these progenitors,
Heimberg says, which may be more like true stem cells.
http://www.sciam.
---
Elusive pancreatic progenitor cells found in mice
January 25, 2008 --New York, NY-- Researchers in Belgium have
significantly advanced the discovery of a pancreatic progenitor cell
with the capacity to generate new insulin-producing beta cells. If
the finding made in mice holds for humans, the newfound progenitor
cells may represent "an obvious target for therapeutic regeneration
of beta cells in diabetes," the researchers report in the Jan. 25
issue of the research journal Cell, a publication of Cell Press. In
people with type 1 diabetes, blood sugar rises due to a loss of the
insulin-producing pancreatic beta cells. Insulin is a hormone that
helps the body use glucose for energy.
"One of the most interesting characteristics of these [adult]
progenitor cells is that they are almost indistinguishable from
embryonic progenitor cells," said Harry Heimberg at the Juvenile
Diabetes Research Foundation Center at Vrije Universiteit Brussel in
Belgium and the Beta Cell Biology Consortium. "In terms of their
structure and gene expression, there are no major differences. They
look and behave just like embryonic beta cell progenitors.
"We at JDRF believe that this new research provides novel insights
that may provide therapeutic potential to regenerate beta cells in
type 1 diabetes," said Patricia Kilian, Regeneration Program Director
at JDRF.
Previous studies have suggested the existence of a beta cell
progenitor in the pancreas after birth, but the identification and
characterization of the progenitor cell has not been fully achieved.
Other studies showing that replication of adult beta cells can
account for beta cell turnover and expansion of beta cells under
normal physiologic conditions and called into question the role or
existence of a progenitor cell in regeneration. "Most people gave up
looking because the cells are so few and so hard to activate," added
Heimberg.
In the new study, Heimberg's team tied off a duct that drains
digestive enzymes from the pancreas, a manipulation that led to a
doubling of beta cell mass in the injured part of the pancreas within
two weeks. The animals' pancreases also began producing more insulin,
evidence that the new beta cells were fully functional. Using a
genetic labeling technique, the researchers found that the new beta
cells were derived from precursor cells that expressed a gene
expressed in embryonic progenitor cells called Neurogenin 3 (Ngn3)
and that production of the new beta cells depended on activity of
this gene. He suspects the regenerative process is sparked by an
inflammatory response in the enzyme-flooded pancreas.
"The most important challenge now is to extrapolate our findings to
patients with diabetes," Heimberg reported. Although he cautioned
that any potential diabetes treatment remains in the future, he
said "our findings reveal the significance of investigating the
feasibility of both isolating facultative beta cell progenitors and
newly formed beta cells from human pancreas in order to expand and
differentiate them in vitro and transplant them in diabetic patients
and also composing a mix of factors able to activate beta cell
progenitors to expand and differentiate in situ in patients with an
absolute or relative deficiency in insulin."
###
About JDRF
JDRF (www.jdrf.org) was founded in 1970 by the parents of children
with juvenile diabetes – a disease that strikes children suddenly,
makes them insulin dependent for life, and carries the constant
threat of devastating complications. Since inception, JDRF has
provided more than $800 million to diabetes research worldwide. More
than 80 percent of JDRF' expenditures directly support research and
education about research. JDRF's mission is constant: to find a cure
for diabetes and its complications through the support of research.
Public release date: 25-Jan-2008
Contact: Susan Sherman
ssherman@jdrf.
212-479-7510
Juvenile Diabetes Research Foundation International
http://www.eurekale
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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