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Topic Name: Protective Pouch to Enhance Cell Therapy
Category: Biodesign
Research persons: Tom Link, Sutter of Alpharetta, Ga.;Daniel Chung of Vienna, Va.; Benjamin Kline of St. Louis, Mo.; Kerim Eken of NewYork, N.Y.; Nicholas Gil of Columbus, Ohio; and Joshua Crist of Macedonia, Ohio.Gill and Crist are freshmen.
Location: Johns Hopkins University School of Medicine,733 North Broadway,Baltimore, MD 21205, United States
Details
Johns Hopkins undergraduates have
invented a device to improve cell therapy for diabetes patients by anchoring
transplanted insulin-producing cells inside a major blood vessel.A team of 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 these cells.
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."
Along with other undergraduate
projects, this prototype was unveiled May 2 at the university's Biomedical
Engineering Design Day showcase. The Johns Hopkins Technology Transfer staff
has applied for a provisional patent. Animal testing is expected to begin this
summer. If it is 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 bio- reactor inside the
vein to produce insulin and other proteins that the body needs. The students
have built a housing in which the bio-reactor can operate. I'm pretty optimistic
that it will work in living subjects."
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," said Link, 22, of Holbrook, N.Y. "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 semi-permeable alginate microcapsules - tiny
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 of 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 university's 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 of 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 through.
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
pouch. They also demonstrated that the device causes no pressure drop in the
model blood vessels and that the microcapsules can easily be injected and
withdrawn.
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 of Alpharetta, Ga.; Daniel Chung of Vienna, Va.; Benjamin
Kline of St. Louis, Mo.; Kerim Eken of New York, N.Y.; Nicholas Gil of Columbus,
Ohio; and Joshua Crist of Macedonia, Ohio. Link, Sutter, Chung, Kline and Eken
are seniors. Gill and Crist are freshmen.
Robert H. Allen, an associate research
professor in the Department of Biomedical Engineering, was technical advisor for
this project and director of the design course.
About Researchers:
Aravind Arepally
Dr. Aravind
Arepally is an Assistant Professor of Radiology and Surgery at the Johns Hopkins
University School of Medicine. Dr. Arepally obtained his undergraduate
degree from the Mercer University with a degree in Mathematics. He
subsequently graduated from the Emory University School of Medicine in 1993. He
received his diagnostic radiology training at Emory University Hospital. He
continued his training at Johns Hopkins Medical Institutes where he was a fellow
in Cardiovascular and Interventional Radiology. Upon completion of his
training, he joined the department as full time faculty.His research interests
include basic science research, clinical research, and device development. In
the basic science arena, he is investigating the use of MRI to perform novel
vascular procedures. He hopes to be able to develop new therapies utilizing MRI
that are currently not feasible with current technology. His clinical research
interests include problems related to the cardiovascular system, in particular,
new pharmacologic drugs available for the treatment of vascular disease. He
is also working with the Johns Hopkins School of Biomedical Engineering on
projects related to new minimally invasive devices.
Jeff W. M. Bulte
Staff
Scientist, F.M. Kirby Research
Center for Functional Brain Imaging
Kennnedy Krieger Institute
Professor,
Dept. of Radiology, Johns Hopkins University
Director
of Cellular Imaging, Institute for Cell Engineering
Affiliations: International
Society of Magnetic Resonance in Medicine,
Robert H. Allen
Robert Allen , Ph.D. is a senior
lecturer in biomedical engineering at Johns Hopkins University, where he directs
a university based corporation called Homewood Biomedical Design Associates (HBDA).
Within HBDA, teams of biomedical engineering students enrolled in design courses
serve as project engineers by designing and developing practical prototypes for
customers, which include Hopkins faculty, medical researchers and handicapped
individuals.A professional engineer in three states, Allen taught team based
design courses at the University of Houston and the University of Delaware prior
to coming to Hopkins. His research interests include birth mechanics and
modeling; he has authored or co-authored over thirty journal publications and a
number of book chapters, and has generated more than $800K in external support
for research and teaching. More than two dozen of Allen’s students or advisee
teams of students have garnered national design awards for projects they have
developed.
In the Images:
1.The students tested their cell therapy pouch after inserting
it in latex tubing that represented the portal vein, where the device may
someday be implanted in humans to treat diabetes.
Photo by Will Kirk
2.The student-designed cell therapy pouch is formed by two
concentric stents, similar to the ones used to keep clogged blood vessels open.
A band of nylon mesh surrounds the inner stent and holds the microcapsules
containing helpful cells.
Photo by Will Kirk
.3.Johns Hopkins undergraduates developed a device, at right,
to anchor therapeutic cells within a blood vessel, where they can release
insulin and other proteins. The cells live within protective microcapsules, seen
floating in the vial at left.
Photo by Will Kirk
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