The
Micro/Bio/Nanofluidics Unit at OIST has developed a novel microfluidic platform
that allows to
encapsulate small particles or cells with alginate capsules.
(December 25, 2015) Diabetes
is one of the leading causes of death. Patients with type 1 diabetes have their
insulin secreting cells destroyed by the immune system and require daily
insulin injections. Pancreatic islet transplantation is an effective treatment
that can dramatically reduce daily doses or even eliminate dependence on
external insulin. Insulin producing cells are injected into a recipient liver.
After an adaptation period they start to produce sufficient hormone needed by
diabetic patients.
However, while the transplantation procedure itself has been
greatly improved in recent years, collection, preservation, and transportation
of these cells are still very challenging. Research published in Advanced
Healthcare Materials by the scientists from the Okinawa Institute of Technology
and Science Graduate University (OIST) in collaboration with the University of
Washington and Wuhan University of Technology offers a solution for some of
these problems.
Production and secretion of insulin occur in the pancreas —
an endocrine gland in the digestive system. Cells secreting insulin are
clustered in pancreatic islets. Despite their crucial role in organismal
wellbeing these islets comprise only a few percent of the pancreatic tissue.
The islet transplantation does not require major surgical intervention and is
often done under local anaesthesia. It is also cheaper and might be safer than
transplantation of the entire pancreas. Unfortunately, so far, only human islets
can be transplanted and their supply is but a trickle.
Schematic
representation of the pancreatic islet cryopreservation method
developed by a
multidisciplinary group of researchers led by Prof. Shen.
Cryopreservation, or deep freezing, is the method commonly
used for the islet preservation and transportation. But it is not completely
safe. One might think that storage at temperatures below -190°C is the most
dangerous phase. However, the cells are very good at enduring it. It is the
freezing process (-15 to -60°C) itself that poses the most challenges. As the
cells are cooled, water in and around them freezes. Ice crystals have sharp
edges that can pierce membranes and compromise cell viability. This also
becomes problematic during thawing.
A multidisciplinary group of researchers led by Prof. Amy
Shen, head of the Micro/Bio/Nanofluidics Unit at OIST, developed a novel
cryopreservation method that not only helps to protect pancreatic islets from
ice damage, but also facilitates real-time assessments of cell viability.
Moreover, this method may reduce transplant rejection and, in turn, decrease
use of immunosuppressant drugs, which can be harmful to patient health.
The novel technique employs a droplet microfluidic device to
encapsulate pancreatic islets in hydrogel made of alginate, a natural polymer
extracted from seaweed. These capsules have a unique microstructure: a porous
network and considerable amount of non-freezable water. There are three types
of water in the hydrogel: free water, freezable bound water, and non-freezable
bound water. Free water is regular water: it freezes at 0°C, producing ice
crystals. Freezable bound water also crystallises, but the freezing point is
lower. Non-freezable bound water does not form ice due to the strong
association between water molecules and the hydrogel networks. Hydrogel
capsules with large amounts of non-freezable bound water protect the cells from
the ice damage and reduce the need for cryoprotectants — special substances
that minimise or prevent freezing damage and can be toxic in high
concentrations.
Another innovation, proposed by the group, is the use of a
fluorescent oxygen-sensitive dye in hydrogel capsules. The porous structure of
the capsules does not impede oxygen flow to the cells. And this dye functions
as a real-time single-islet oxygen sensor. Fluorescence indicates whether cells
are consuming oxygen and, therefore, are alive and healthy. It is a simple,
time-efficient, and cheap method of assessing viability, both of individual
islets or populations thereof.