Diabetes researchers,
investigating how the body supplies itself with insulin, discovered to
their surprise that adult stem cells, which they expected to play a crucial
role in the process, were nowhere to be found. Many researchers had
proposed that adult stem cells develop into insulin-producing cells, called
beta cells, in the pancreas.
Instead, the beta cells themselves divide, although slowly, to
replenish their own population.
"Ultimately, if diabetes researchers learn how to control insulin
production, we can better treat patients who now can't produce insulin --
children and adults with type 1 diabetes," said study leader Jake A.
Kushner, M.D., a pediatric endocrinologist at The Children's Hospital of
Philadelphia. "This research tells us that we need to better understand
what regulates the growth of beta cells, rather than searching for adult
stem cells that give rise to beta cells."
Dr. Kushner's team reported their findings, based on animal studies, in
the May issue of Developmental Cell.
The discovery does not have immediate implications for diabetes
treatment. Rather, it advances basic knowledge of insulin biology that
could form a foundation for eventual therapies.
Currently, patients with type 1 diabetes depend on life-saving insulin
injections or medication. Looking to future techniques, medical researchers
hope to fulfill a promise of regenerative medicine: restoring the body's
ability to produce its own insulin. One solution is to transplant tissues
called the islets of langerhans, small masses within the pancreas
containing the beta cells that normally secrete insulin. Islet transplants
have already been performed experimentally, but typically fail after a few
years in a patient's body.
Moreover, islets are taken from cadavers, and supplies are very
limited, so researchers are seeking ways to grow islets in the laboratory.
Another potential implication of the research is for beta cell
regeneration, a controversial area of diabetes research. Patents with
longstanding type 1 diabetes have small amounts of islets that escape
destruction by the immune system. With sufficient biological knowledge and
the appropriate techniques, it might even be possible to someday stimulate
these residual beta cells inside patients to proliferate and produce
healthy amounts of insulin.
"We expected to find adult stem cells that differentiate into beta
cells," said Kushner. "Such adult stem cells are important in renewing
skin, intestines and other tissues." (Adult stem cells are different from
the embryonic stem cells found in human embryos that are a current focus of
social and political controversies.)
"However," he added, "we found no evidence for adult stem cells that
give rise to beta cells or other pancreatic tissue. We found that all beta
cells can replicate, and are, in a sense, their own stem cells."
Kushner's group found that beta cells renew themselves and grow slowly.
Unexpectedly, the researchers found the beta cells undergo a prolonged
waiting period before dividing. This delay, which they call a replication
refractory period, had never been observed in mammalian development.
The researchers made use of a novel cell labeling technique that allows
them to view the fates of individual cells throughout multiple rounds of
cell divisions. "Although the cell labeling technique had been described
previously by other groups, our group was the first to use it over long
periods of time," said Kushner.
By providing rats with a timed sequence of colored dyes in their
drinking water, the researchers were able to see discrete beta cells in the
rat pancreas, shining in single colors that indicated a sequence of cell
divisions. In contrast, the rapidly dividing cells in the rats' intestine
showed blended colors, indicating that they had divided multiple times from
specialized cells-possibly from adult stem cells.
"We expect that other developmental biologists can use this cell
labeling technique to track the fate of cells in many other tissues, such
as brain and muscle," said Kushner, adding that the technique may also be
useful in following cells in cancer research.
If these findings open up a new avenue of investigation into how
insulin- producing cells develop, diabetes researchers may be a step closer
to manipulating the process to benefit patients. "This research also has
implications for type 2 diabetes, in which the body fails to produce and
respond to insulin," added Kushner. The incidence of type 2 diabetes has
been rising dramatically, especially among children and adolescents.
The study was supported by the Juvenile Diabetes Research Foundation
International, the National Institutes of Health, the March of Dimes and
the Lawson Wilkins Pediatric Endocrine Society.
In addition to his position at The Children's Hospital of Philadelphia,
Dr. Kushner is an assistant professor of Pediatrics at the University of
Pennsylvania School of Medicine. His co-authors, all from the Children's
Hospital Division of Endocrinology and the Penn School of Medicine, are
Monica Teta, Matthew M. Rankin, Simon Y. Long and Geneva M. Stein.
About The Children's Hospital of Philadelphia:
The Children's Hospital
of Philadelphia was founded in 1855 as the nation's first pediatric
hospital. Through its long-standing commitment to providing exceptional
patient care, training new generations of pediatric healthcare
professionals and pioneering major research initiatives, Children's
Hospital has fostered many discoveries that have benefited children
worldwide. Its pediatric research program is among the largest in the
country, ranking third in National Institutes of Health funding. In
addition, its unique family-centered care and public service programs have
brought the 430-bed hospital recognition as a leading advocate for children
and adolescents. For more information, visit chop.
Children's Hospital of Philadelphia
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