Georgia Tech engineers and Emory
University clinicians have successfully
engrafted insulin-producing cells into a
diabetic mouse model, reversing diabetic
symptoms in the animal in as little as 10
days.
The research team engineered a
biomaterial to protect the cluster of
insulin-producing cells -- donor pancreatic
islets -- during injection. The material also
contains proteins to foster blood vessel
formation that allow the cells to
successfully graft, survive and function
within the body.
"It's very promising," said Andrés Garcia,
Georgia Tech professor of mechanical
engineering. "There is a lot of excitement
because not only can we get the islets to
survive and function, but we can also cure
diabetes with fewer islets than are
normally needed."
The research article -- a partnership with
Emory's Dr. Robert Taylor and Dr. Peter
Thule that was funded in part by the
JDRF, the leading global organization
funding Type 1 diabetes research -- will
be published in the June issue of the
journal Biomaterials.
Organizations such as JDRF are dedicated
to finding a cure for Type 1 diabetes, a
chronic disease that occurs when the
pancreas produces little or no insulin, a
hormone that allows the transport of
sugar and other nutrients into tissues
where they are converted to energy
needed for daily life.
Pancreatic islet transplantation re-
emerged as a promising therapy in the
late 1990s. Patients with diabetes
typically find it difficult to comply with
multiple daily insulin injections, which
only partially improve long-term
outcomes. Successful islet transplantation
would remove the need for patients to
administer insulin. While islet
transplantation trials have had some
success, and control of glucose levels is
often improved, diabetic symptoms have
returned in most patients and they have
had to revert to using some insulin.
Unsuccessful transplants can be attributed
to several factors, researchers say. The
current technique of injecting islets
directly into the blood vessels in the liver
causes approximately half of the cells to
die due to exposure to blood clotting
reactions. Also, the islets -- metabolically
active cells that require significant blood
flow -- have problems hooking up to blood
vessels once in the body and die off over
time.
Georgia Tech and Emory researchers
engineered a hydrogel, a material
compatible with biological tissues that is a
promising therapeutic delivery vehicle.
This water-swollen, cross-linked polymer
surrounds the insulin-producing cells and
protects them during injection. The
hydrogel containing the islets was
delivered to a new injection site on the
outside of the small intestine, thus
avoiding direct injection into the blood
stream.
Once in the body, the hydrogel degrades
in a controlled fashion to release a growth
factor protein that promotes blood vessel
formation and connection of the
transplanted islets to these new vessels.
In the study, the blood vessels effectively
grew into the biomaterial and successfully
connected to the insulin-producing cells.
Four weeks after the transplantation,
diabetic mice treated with the hydrogel
had normal glucose levels, and the
delivered islets were alive and
vascularized to the same extent as islets
in a healthy mouse pancreas. The
technique also required fewer islets than
previous transplantation attempts, which
may allow doctors to treat more patients
with limited donor samples.
Currently,
donor cells from two to three cadavers
are needed for one patient.
While the new biomaterial and injection
technique is promising, the study used
genetically identical mice and therefore
did not address immune rejection issues
common to human applications. The
research team has funding from JDRF to
study whether an immune barrier they
created will allow the cells to be accepted
in genetically different mice models. If
successful, the trials could move to larger
animals.
"We broke up our strategy into two
steps," said Garcia, a member of Georgia
Tech's Petit Institute for Bioengineering
and Bioscience. "We have shown that
when delivered in the material we
engineered, the islets will survive and
graft. Now we must address immune
acceptance issues."
Most people with Type 1 diabetes
currently manage their blood glucose
levels with multiple daily insulin injections
or by using an insulin pump. But insulin
therapy has limitations. It requires
careful measurement of blood glucose
levels, accurate dosage calculations and
regular compliance to be effective.
This work was also funded by the
Regenerative Engineering and Medicine
Center at Georgia Tech and Emory, and
the Atlanta Clinical and Translation
Science Institute under PHS grant UL
RR025008 from the Clinical and
Translational Science Award Program.
The Center for Pediatric Healthcare
Technology Innovation at Georgia Tech,
the Department of Veterans Affairs Merit
Review Program and the National
Institutes of Health's National Institute of
Diabetes and Digestive and Kidney
Diseases (Grant R01 DK076801-01)
helped fund the project as well.
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