Technion researchers cure mice of diabetes in novel trial
New research investigates the use of an autograft of muscle cells engineered to take in sugar at increased rates in mice with type 2 diabetes.
The implanted construct: the engineered muscle fibers (in red) express the GLUT4 (in green)
(photo credit: TECHNION SPOKESPERSON'S OFFICE)
A team of researchers at the Technion-Israel Institute of Science
have used genetically engineered muscle tissue to cure mice of type 2
diabetes, according to a report published in the peer-reviewed journal Science Advances.
Muscle
cells are among the main targets of insulin, and they are supposed to
absorb sugar from the blood. However, in type 2 diabetics, the ability
of these cells to absorb sugar is reduced.
Restoring
the metabolic activity of skeletal muscle could therefore provide a
cure for the disease. But, until now, it has been an unexplored optional
therapy.
For the past five years, Prof. Shulamit Levenberg and doctoral
student Rita Beckerman from the Stem Cell and Tissue Engineering
Laboratory in the Technion’s Faculty of Biomedical Engineering have been
developing and testing the use of an autograft of muscle cells
engineered to take in sugar at increased rates in mice with type 2
diabetes.
Prof. Shulamit Levenberg (credit: TECHNION SPOKESPERSON'S OFFICE)
Specifically,
they isolated muscle cells from mice and then overexpressed the GLUT4
transporter in the cells and created metabolically functional,
engineered muscle tissue – tissue that was seeded on polymeric
biodegradable scaffolds and cultured up to three weeks – and then
ultimately transported back into the abdomen of the diabetic mice.
The
results were that not only did the engineered cells proceed to absorb
sugar correctly, improving blood sugar levels, Levenberg explained, but
they also induced improved absorption in the mice’s other muscle cells
by means of signals sent between them.
Rita Beckerman (credit: TECHNION SPOKESPERSON'S OFFICE)
The mice remained cured of diabetes for the entire four-month period that they were under observation.
“These
cells worked hard and absorbed glucose, and also secreted factors that
systematically affected the metabolism of the mice,” Levenberg said. In
addition to their blood-glucose levels being stabilized, the mice showed
other improvements, like less lipids in their livers.
Prof. Shulamit Levenberg (left) and doctoral student Rita Beckerman (credit: TECHNION SPOKESPERSON'S OFFICE)
She said, “The approach can be used to rescue mice from their
diabtetic situation, and now we hope to be able to use it in the future
as a treatment for humans.”
The
muscle cells could be taken from patients by biopsy, she said, adding
that using cells from the patient itself and then transporting them back
would help eliminate the risk of rejection.
Diabetes
currently affects around 34 million Americans, the Technion said in a
release. Some 90% of them suffer from type 2 diabetes. People with the
disease are often plagued by long-term complications, ranging from heart
disease and strokes to damage to the retina that can cause blindness
and kidney failure, among other challenges. The disease is associated
with up to a 10-year reduction in life expectancy.
There
is currently no cure for type 2 diabetes. It is treated mainly by a
combination of lifestyle and diet changes, medication and insulin
injections.
“An
effective treatment – and one that is a one-time treatment rather than
daily medication – could significantly improve both quality of life and
life expectancy of those who have diabetes,” the Technion release said.
“The same method could also be used to treat various enzyme deficiency
disorders.”
Levenberg
said that the next step is to show that it works using human cells in
the lab. After that, they could move to human trials, though she said
this is still “several years away.”
The
research was funded by Rina and Avner Schneur as part of the Rina and
Avner Schneur Center for Diabetes Research. The foundation had
approached Levenberg’s lab
in search of a team willing to start research in a new direction not
yet in the field. Levenberg said that they decided “to take the
challenge on ourselves.”
“It
was a high risk to take,” she admitted. “This is a totally
out-of-the-box approach. But it shows why sometimes it is important to
get funds for research when it is just an idea.
“If
you have the resources you can go and try,” she continued. “We were
lucky to be able to do it and to show that indeed this might work.”
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