Researchers at Johns Hopkins have found a way to
overcome a major stumbling block to developing successful
insulin-cell transplants for people with type I
diabetes.
Traditional transplant of the cells, accompanied by
necessary immune-suppressing drugs, has had highly variable
results, from well- to poorly tolerated. Part of the
problem, the researchers say, is an inability to track the
cells — so-called pancreatic beta cells — once
they're inside the body.
Now a new technique encloses the insulin-producing
cells in magnetic capsules, using an FDA-approved iron
compound with an off-label use, that can be tracked by
magnetic resonance imaging. The product, tested in swine
and diabetic mice, also simultaneously avoids rejection by
the immune system, likely a major reason for transplant
failure. The work was published online July 29 in Nature
Medicine.
"We're really excited because we can track where we
put the cells and make sure their protective housing stays
intact and that the cells don't move. This could solve the
mystery of why current transplantation techniques work only
for so long," said Aravind Arepally, assistant professor of
radiology and surgery
and one of the study's authors.
Type I diabetes — the most common childhood sort
— causes a person's immune system to destroy the
pancreatic beta cells that make insulin. Without insulin,
blood sugar levels can become dangerously high and lead to
complications that include blindness or kidney failure.
Careful monitoring of blood sugar levels paired with
insulin injections can manage the condition, but
transplanting healthy beta cells holds more promise for the
moment-to-moment fine-tuning of insulin levels, Arepally
says.
Current experimental cell transplantation techniques
are done "naked and blind," only lasting a short period of
time, according to co-author Jeff Bulte, a professor of
radiology and
chemical and biomolecular engineering. The unprotected
transplanted cells are vulnerable to attack by the
recipient's immune system, and researchers cannot see the
cells to figure out why they stop making insulin after a
while.
To address both of these challenges, the research team
captured beta cells in tiny porous capsules made from a
mixture of alginate, a gooey material made from seaweed,
and Feridex, a magnetic iron-containing material visible
under MRI. They then used a machine that oozes droplets of
this mixture to surround and encapsulate individual islet
clusters, each containing about 500 to 1,000
insulin-producing beta cells. Once the cells were
encapsulated, the shell hardened, creating a
"magnetocapsule" that measures less than 1/128 of an inch
across.
"They're tiny spheres with nano-scale pores just big
enough to let the good stuff out but keep the bad from
getting in," said lead author Brad Barnett, a medical
student and Howard Hughes fellow at Johns Hopkins. The
openings in the magnetocapsule are so small that the body's
immune system sentinels cannot reach and attack the
transplanted cells.
The team first transplanted magnetocapsules into the
abdomens of mice engineered to develop diabetes. Blood
sugar levels in the animals returned to normal within a
week and stayed that way for more than two months. In
contrast, more than half of untransplanted diabetic mice
died, and the rest had very high blood sugar levels.
To mimic human transplantation, the researchers then
implanted magnetocapsules into the livers of swine with the
help of MRI fluoroscopy, special reflective screens and a
computer monitor that provides real-time imaging. The liver
— rather than the usual pancreatic home of beta cells
— was chosen because it contains many blood vessels
that can deliver insulin quickly to the rest of the body.
The team threaded a long needlelike tube into a large vein
near the upper thigh and guided the tube upward, across and
into a neighboring blood vessel, ending in the body of the
liver.
The pigs underwent MRI and blood tests three weeks
after magnetocapsule transplantation. MRI showed that the
magnetocapsules remained intact in the liver, and blood
tests revealed that the cells were still secreting insulin
at levels considered functional in people.
"We hope that our magnetocapsules will make
tissue-type matching and immunosuppressive drugs problems
of the past when it comes to cell-based therapies for type
1 diabetes," Bulte said.
The research was funded by the National Institutes of
Health and the Howard Hughes Medical Institute.
Authors on the paper are Barnett, Arepally, Parag
Karmarkar, Di Qian, Wesley Gilson, Piotr Walczak, Valerie
Howland, Leo Lawler, Cal Lauzon, Matthias Stuber, Dara
Kraitchman and Bulte, all of Johns Hopkins.
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