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November 22nd, 2009
Experts agree that islet encapsulation is a promising concept for making the benefits of islet transplantation available to people suffering from diabetes without the use of immunosuppressant drugs. The capsules come in two types. A capsule containing a single islet is called a microcapsule; one that contains many islets is a macrocapsule. The macrocapsule is safer, because it is easier to retrieve a larger device such as the macrocapsule than a smaller one such as the microcapsule, should the islets fail. But most successful encapsulation islet transplants have used microcapsules, not macrocapsules. Why?
In short, because macrocapsules need to be extremely thin in order to keep the enclosed islets alive, and achieving sufficient thinness is difficult.
All cells are naturally bathed in nutrients delivered by blood circulation. The smallest blood vessels are capillaries, so small that red blood cells can only just squeeze through. The clear liquid part of blood, plasma, delivers soluble nutrients like sugars and amino acids and carries away cell secretions like insulin. Oxygen is delivered by red blood cells because it does not dissolve very well in water, but instead is highly soluble in the iron-bearing hemoglobin that fills red blood cells.
Capillaries that deliver the oxygen are found throughout the body, delivering nutrients to hungry cells. The more oxygen a tissue consumes, the closer together you find capillaries. The islets of Langerhans are unusually active, and need more nutrients than the surrounding tissue. It is estimated that islets consume more than 10% of the nutrients in the pancreas even though they make up less than 2% of the mass.
There are no capillaries in encapsulated islets, so it would seem that no nutrients are delivered into them. Without blood circulation, oxygen levels fall and the islets starve and die. However, oxygen in the tissue surrounding the capsules diffuses to the hungry islets cells inside the capsule.
Diffusion always occurs down a gradient, that is, from a place of high concentration to a place of low concentration. If you spot a big drop of blood onto white fabric you can watch the red color move out to a large drop. That is what diffusion is like.
Fortunately, diffusion is a well-understood physical process, and can be modeled in computer simulations. In a capsule (micro or macro), the greatest oxygen level is found right at the surface. Oxygen level declines as your move through the outer membrane toward the islet in the capsule; when you reach the living tissue the oxygen level begins to plunge. This is because the cells are consuming the oxygen and there is less available for the cells at the center of the islets, farther from the surface of the capsule.
The photograph shows the dramatic effect of diffusion on the islets. This islet was suspended in a gel to simulate the environment of a capsule. The top picture shows the islet immediately after encapsulation. The lower one shows the islet six days later. The black sphere at the center of the islet is dead islet cells. The limited oxygen available by diffusion has all been used by the cells near the edge of the islet; the cells at the core have died of oxygen starvation. Showing that if the protecting capsule is too thick it will not allow proper diffusion.
Computer models show that oxygen can diffuse about ¼ of a millimeter (250 microns) into living tissue, and it is no coincidence that capillaries are less than 250 microns apart in living tissue. This means that a microcapsule must be less than 400 microns in diameter to keep all the islet cells alive. Making micro capsules that size is not difficult. But making a macro capsule, which also needs to be thinner than 400 microns, is a huge challenge.
Cerco Medical’s product—a macrocapsule— is called the Islet Sheet; the scientific name is thin sheet macrocapsule (TSM). The Islet Sheet is about 4cm in length, about the size of a business card. With a thickness of 400 microns (0.04 cm) our thin sheet macrocapsule is a hundred times wider than it is thick. And to ensure biocompatibility, its surface is ultra-smooth.
The Islet Sheet is unique and patented. It is the only microcapsule that is sufficiently thin and smooth as well as big enough to hold enough islets. We believe that our Islet Sheet TSM is the only capsule that is both retrievable and fully functional, making it superior to microencapsulation.