Encapsulated islets being invaded by immune cells.

Electron micrograph of a canine Islet Sheet.

The Bioartificial Pancreas

“Development of a ‘bioartificial pancreas’ that housed islets, protected them from the immune system, and encouraged their growth would be a major step forward for transplantation.”

—Kelly Close, in Targeting a Cure

A bioartificial pancreas—a device that encapsulates and nurtures islets of Langerhans— replaces the islets and beta cells destroyed by type 1 diabetes. Implanted in the peritoneal cavity or under the skin, it contains about a million islets. It responds to changing blood glucose levels by releasing hormones, chiefly insulin.

Any bioartificial pancreas is fabricated from living and nonliving components. The living component is the islets, which sense glucose levels and secrete insulin according to normal physiology. The nonliving component shields the islets from the diabetic’s body and its destructive immune mechanisms, yet permits the islets inside to thrive.

Several Approaches

Medical technology firms, working with researchers, have tried various ways to create a bioartificial pancreas that performs as it should, using physical configurations such as coatings, capsules, hollow fibers and sheets. Microencapsulated, or “coated,” islets are the first-generation bioartificial pancreas. Their advantage is that nutrients can easily move into the islets and insulin can move out. Among the drawbacks is that they are hard to remove because they don’t stay in one place.

Macroencapsulation, another approach, groups islets cells together in a larger package. Such devices tend to be more stable and easily extracted, but—at least in their earlier capsule form—may restrict the free passage of nutrients and insulin. This “starves” the beta cells and impedes the goal of controlling blood glucose.

Technical Challenges

As you can see, the technical requirements for a bioartificial pancreas are exacting, and they have proven very hard to solve. The critical issues are:

  • Avoiding the foreign-body response. Most often the surface of the bioartificial pancreas provokes a fibrotic reaction that walls off the device, so the islets cannot get nutrition and the bioartificial pancreas dies of starvation.
  • Enabling oxygen to penetrate to the core of the device. The dimensions of most bioartificial pancreases don’t allow free passage of vital oxygen.
  • Fabricating the device without damaging the islets. Sometimes the process destroys too many islets for the bioartificial pancreas to function.
  • Placing the device in close proximity to blood vessels, which deliver oxygen and nutrients to the islets and carry secreted insulin to the rest of the body.

Various techniques are being explored to extend the life and efficacy of transplanted islets. Some researchers are attempting to build into the device helpful biochemical nutrients that release slowly. Other are focusing on the shape and configuration of the bioartificial pancreas.

An Islet “Sheet”

The research project supported by Hanuman has advanced the field with a radically thin device that meets most of the technical challenges.

About the size of a business card, the Islet Sheet is the product of 30 years of experimentation and study by Islet Sheet Medical Company and its research associates. It consists of a layer of human islets “macroencapsulated” within a membrane of ultra-pure alginate (derived from seaweed). The sheet membrane is reinforced with mesh and coated on the surface to prevent contact between the cells inside and the host’s immune attackers. Oxygen, glucose, and other nutrients diffuse readily into the sheet, keeping the islets alive; insulin, hormones, and waste products diffuse out. The Islet Sheet may be removed or replaced at any time. And except for a brief period after transplantation, no immune suppression drugs are needed.

Read more about the Islet Sheet Project.

Takeaways

  • A bioartificial pancreas is an implanted device that encapsulates and protects islets, functioning like a real pancreas to release insulin and control blood sugar.
  • The two main types use microencapsulated (individual) or macroencapsulated (“packaged”) islets. Each has pros and cons.
  • Avoiding an immune reaction while providing nutrients to the islets are among the tough technical challenges to a viable bioartificial pancreas, but we believe the Islet Sheet comes closest to solving them.