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New data from NIH lab confirms protocol
to reverse type 1 diabetes in mice
Data also support role for adult
spleen cells in regeneration of beta cells
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BOSTON - November 23, 2006 - New data published in the Nov.
24 issue of Science provide further support for a protocol
to reverse type 1 diabetes in mice and new evidence that adult precursor
cells from the spleen can contribute to the regeneration of beta
cells. In 2001 and 2003, researchers at Massachusetts General Hospital
(MGH) demonstrated the efficacy of a protocol to reverse of type
1 diabetes in diabetic mice. Three studies from other institutions
published in the March 24, 2006 issue of Science confirmed
that the MGH-developed protocol can reverse the underlying disease
but were inconclusive on the role of spleen cells in the recovery
of insulin-producing pancreatic islets. The new data from a study
performed at the National Institutes of Health (NIH), published
as a technical comment, provides additional confirmation of the
ability to reverse type 1 diabetes and on the role of the spleen
cells in islet regeneration.
"This data from the NIH and the earlier studies have added
significantly to the understanding of how diabetes may be reversed,"
says Denise Faustman, MD, PhD, director of the Immunobiology Laboratory
at Massachusetts General Hospital, primary author of the 2001 and
2003 studies and co-corresponding author of the current report.
"It is still early, but it appears that there are multiple
potential sources for regenerating islets. As a research community
we should pursue all avenues. We're excited to see what will happen
in humans."
In the 2001
and 2003
studies, Faustman and colleagues treated end-stage nonobese diabetic
(NOD) mice with Freund's complete adjuvant, a substance that suppresses
the activity of the immune cells that destroy islets in type 1 diabetes.
They also introduced donor spleen cells to retrain the immune system
not to attack islets and found that the protocol not only halted
the immune destruction caused by diabetes but also allowed the insulin-producing
pancreatic islet cells to regenerate. Evidence indicated that the
spleen cells were the source of at least some of the regenerated
islet cell and hastened the restoration of blood sugar levels.
The direct contribution of spleen cells to islet recovery, first
described in the 2003 study, is confirmed in the current work. NIH
researchers used cell lineage tracking in the form of Y-chromosomal
fluorescence in situ hybridization (FISH), in combination with insulin
staining, to follow the fate of male spleen cells transplanted into
female recipients. The female mice that received male donor cells
consistently showed Y-chromosome-positive insulin-producing islet
cells, indicating that the introduced spleen cells contribute to
islet recovery. The current study also showed that the degree of
spleen cell contribution is influenced by mouse age at the start
of treatment. Spleen cells appear to contribute to islet recovery
more in mice who are older and with more advanced diabetes compared
with younger mice with less advanced diabetes, in which regeneration
of remaining islets may be the dominant mechanism.
The research to support the new data was conducted at the NIH laboratory
of Eva Mezey, MD, PhD, co-corresponding author of the report. It
was funded by the Sjogren's Syndrome Foundation, National Institutes
of Health/NIDCR intramural program, Canadian Institutes of Health
Research and Canada Research Chair. The three studies published
in March 2006 were supported by the Juvenile Diabetes Research Foundation.
Faustman's research at Massachusetts General Hospital and an upcoming
clinical trial have been supported by The Iacocca Foundation and
other donors.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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