A team of Johns Hopkins undergraduates has invented a
device to improve cell therapy for diabetes patients by
anchoring transplanted insulin-producing cells inside a
major blood vessel.
The five seniors and two freshmen, working with Johns
Hopkins doctors and engineers, devised a protective "pouch"
that should fit inside the portal vein, which feeds into
the liver. This pouch would keep microcapsules of
therapeutic cells in one place, allowing them to thrive and
send out needed insulin. The inventors say the same
approach could be used in cell therapy for other ailments,
including liver disease.
"I think it's a brilliant idea," said one of the
project's sponsors, Jeff W.M. Bulte, director of the
Cellular Imaging Section in the Johns Hopkins Institute
for Cell Engineering.
The pouch is formed by sandwiching a porous band of
nylon mesh between two concentric metal stents, similar to
the ones used to keep clogged blood vessels open. Once the
stents are in place, microcapsules filled with helpful
cells are injected into the gap between the stents, where
they become trapped within the nylon mesh. Blood flowing
through the vessel should nourish the encapsulated cells
and circulate the proteins, such as insulin, produced by
The project is important because it could lead to
better results from cellular therapy, in which live cells
are injected to repair or replace damaged or depleted
tissue. "It's a device," Bulte said, "that allows the
microcapsules to be removed and reinserted if additional
therapy is needed — a 'yearly refill,' for example
— and the
students have provided an ideal environment in which the
encapsulated cells can thrive."
This prototype was unveiled, along with other
undergraduate projects, at the university's Biomedical
Engineering Design Day showcase on May 2. The Johns Hopkins
Technology Transfer staff has applied for a provisional
patent. Animal testing is expected to begin this summer
and, if successful, human trials would follow.
"It's very impressive," said Aravind Arepally, an
interventional radiologist, who served as the project's
other sponsor. "We're basically creating a small bioreactor
inside the vein to produce insulin and other proteins that
the body needs. The students have built a housing in which
the bioreactor can operate. I'm pretty optimistic that it
will work in living subjects."
The outer stent is made of
stainless steel. The inner one, made of nitinol, is covered
by a band of nylon mesh. The cell therapy "pouch" is
created in the gap between the two stents.
Photo by Will Kirk / HIPS
The leader of the student design team, Tom Link, said
he selected this project because it has the potential to
benefit many people. "It could provide an important new way
to treat diabetes and fulminant liver failure," Link said.
"I know about the health problems associated with diabetes
because my grandmother has it, and she has to give herself
several shots a day. If it works, this cell therapy could
eliminate the need for that."
Progress in cell therapy has been slow for several
reasons. First, the injected cells are often attacked by a
patient's immune system. Also, the injected cells cannot
survive long without plentiful oxygen and nutrients, which
are not available throughout the body. Finally, once they
are inside the patient, the injected cells need to settle
in a place where they can provide effective treatment
without interfering with healthy body functions.
Arepally and Bulte have overcome some of these hurdles
by working with semipermeable alginate microcapsules
spheres that surround the injected cells and protect them
from the body's immune system. At the same time, the
spheres allow beneficial proteins to flow out and oxygen
and glucose to flow freely in. Arepally and Bulte, both
faculty members in the Russell H. Morgan
Department of Radiology and Radiological Science in the
Johns Hopkins School of Medicine, also have developed ways,
covered by a pending patent, to track the microcapsules
with various imaging technologies.
They and researchers elsewhere have struggled,
however, to keep these encapsulated cells alive within the
body, mainly because the cells often situate themselves
where they do not have access to a plentiful blood supply.
To address this challenge, the radiologists last year asked
undergraduates in the BME Design Team course to devise a
way to keep the microcapsules in one place where their
cells could thrive and deliver effective therapy.
During the past school year, the engineering students
researched the topic, tested biomaterials and constructed
the prototype, designed to fit inside the portal vein. This
large blood vessel, about the diameter of an index finger,
carries blood from the digestive system into the liver.
The pouch components are made to be compressed and
inserted with catheters that a physician can snake into the
abdomen through the femoral vein in the leg. Using
real-time imaging technology, an interventional radiologist
can view and guide the minimally invasive procedure as it
takes place. First, the doctor would insert the stainless
steel outer stent, which would push out harmlessly on the
elastic interior of the vein. Next, the doctor would insert
the inner stent, surrounded by the porous nylon mesh. The
inner stent is made of nitinol, a metal that snaps back
into its original shape after being compressed for
insertion. The inner stent matches the interior diameter of
the vein. When all the pieces are inserted, the nylon mesh
is held snugly against the inner stent. A gap forms between
the mesh and the outer stent, allowing blood to pass
At this point, the physician would use another
catheter to inject the encapsulated cells between the
stents, where the mesh would hold them in place. The tiny
openings in the mesh, each about 250 microns in diameter,
would allow blood to pass through to nourish the cells and
disperse helpful proteins. But the openings are too small
to allow the microcapsules to escape.
In lab tests using latex tubing to represent a vein,
the students used ultrasound imaging to confirm that fluid
can flow smoothly through the mesh and can spread the
microcapsules throughout the pouch. They also demonstrated
that the device causes no pressure drop in the model blood
vessels and that the microcapsules can easily be injected
Link said he and his team members appreciated the
chance to solve a real-world engineering challenge while
drawing on the expertise of prominent researchers such as
Arepally and Bulte. "I don't think I could have found an
opportunity like this anywhere else," he said. "That's one
of the major strengths of Johns Hopkins." Link plans to
continue working on the project in the university's
biomedical engineering master's degree program.
The other student design team members were Edward
Sutter, Daniel Chung, Benjamin Kline, Kerim Eken, Nicholas
Gill and Joshua Crist. Link, Sutter, Chung, Kline and Eken
were seniors. Gill and Crist were freshmen.
Robert H. Allen, an associate research professor in
the Department of
Biomedical Engineering, was technical adviser for this
project and director of the design course.