YSM Issue 91.1

FEATURE biomedical engineering
Defeating
Diabetes
Advances in Cell Encapsulation
Technology
By EMMA HEALY
Art by ANUSHA BISHOP
A young boy is rushed into the Emergency Department after
being discovered unconscious. He’s with his mother, who reports
that earlier that evening, her son had been thirsty, nauseous, and
urinating frequently. He’s now gasping for air, and his breath smells
fruity and sweet, like a sugary pear candy. It’s the smell of ketone
bodies, molecules produced by the liver that cells use as fuel, and
their presence is indicative of ketoacidosis—a dangerous complication
of diabetes. Ketone bodies are acidic, so as they accumulate,
the blood’s pH drops, leading to hyperventilation, nausea, and, in
extreme cases, severe neurological and cardiac complications.
Given his symptoms, the boy likely suffers from type 1 diabetes,
an autoimmune disease in which the patient’s immune system
destroys islet cells in his pancreas. These cells are responsible for
producing insulin, a hormone that helps your body absorb glucose
from the bloodstream. Without sufficient insulin, blood sugar levels
increase and contribute to disease. Diabetic ketoacidosis is a
rapid-onset complication of type 1 diabetes that occurs because
glucose is trapped in the bloodstream, so cells need an alternative
source of energy—the ketone bodies—to keep functioning.
Diabetes treatments focus on maintaining normal insulin levels
with daily injections, which sound easier than they are. These insulin
injections can be uncomfortable, and remembering to keep
to a schedule can be stressful and tiring. Furthermore, figuring out
correct doses can be challenging, as these injections serve multiple
purposes: patients must inject to maintain background levels of insulin,
prepare for meals, and correct high blood sugar. Complicating
the issue, different insulin products act on different time scales,
and each person’s insulin sensitivity is unique. There is always the
risk of overdose, especially after a missed meal, which could lower
blood sugar beyond safe levels. For these reasons, researchers at
Cornell University are improving designs on an alternative treatment
for type 1 diabetes: cell transplantation. “Instead of delivering
insulin through injection, we are trying to develop a technology to
deliver cells, which can sense the glucose concentration and secrete
insulin autonomously,” said Duo An, the PhD candidate at Cornell
who led the research.
As with any transplant procedure, islet cell transplantation has
risks. Since the cells are foreign to the host, the body recognizes
them as invaders and launches an immune response. To prevent
transplant rejection, patients must take immunosuppressive medications
for the remainder of their lives, decreasing their ability to
fight infectious diseases. Despite its dangers, immunosuppression
is often a necessity unless the transplanted cells can be protected
against the host’s immune system, as Cornell’s team is trying to do
with cell encapsulation, a technique where they deliver cells within
special membranes.
Cell encapsulation is not a new procedure. Attempts to coat
transplanted materials with protective membranes occurred in as
early as the 1960s; however, the technology is far from perfect. Even
a current and promising cell encapsulation system, called hydrogel
microcapsules, has a critical flaw: the microcapsules are difficult
to retrieve completely after implantation. “To cure type 1 diabetes
patients, we estimate that 500,000 pancreatic cell aggregates are
required, which means you need to put tens of thousands of these
microcapsules into the patients,” said An. “Because they are individual
microcapsules, it’s almost impossible to retrieve all of the
materials.” Without a better way to remove the microcapsules from
a patient, clinical application of these devices has been restricted. If
the membrane failed or the cells died and the microcapsules could
not be safely removed, the situation could be dangerous to the recipient.
Recognizing this obstacle to cell encapsulation technology,
the Cornell research team sought to design an encapsulation
32 Yale Scientific Magazine March 2018 www.yalescientific.org