Islet transplantation via the portal vein of the liver. Donor islets must be isolated before transplanting, a technically challenging procedure.

Micrograph of a human islet (indicated by the black arrow) still within the pancreas tissue. University of Chicago Medical Center, Witkowski group.

Islet & Pancreas Transplants

Transplantation has been an important field of diabetes research for decades. Therapies include whole-pancreas transplants and various ways of transplanting just the insulin-producing islets of Langerhans of the pancreas. For now, transplants are usually recommended for people whose diabetes is not well controlled by external injected insulin or who have low hypoglycemic awareness (the ability to recognize when blood sugar is low).

About 1,500 pancreas transplants are performed in the U.S. each year. It’s a complex and costly surgical procedure in which a second pancreas is added without removing the first. Because the new pancreas contains fresh islets and beta cells, this can eliminate the need for insulin therapy—and indeed most patients with a successful pancreas transplant are able to be insulin-independent for many years.

A less invasive (but also expensive) method of providing the body with a new supply of beta cells is islet transplantation. Typically this has been done by infusing purified human islets through a major vein that feeds into the liver. Once established, the islets begin producing insulin in response to changing blood sugar levels. Thus far the most clinically advanced islet transplantation technique has been the Edmonton Procotol, introduced in 2000 by a team at the University of Alberta, which has allowed patients to stay insulin-independent for a year or more.

Where Do the Islets Come From?

All forms of islet or pancreas transplants are currently limited by the availability of human islets. Cadavers are the commonest source. Researchers (in New Zealand especially) are using pig islets, which closely resemble the human kind. Future prospects include creating beta cells from other cells in the patient’s own body or—ideally—synthesizing them from stem cells.

Immune Suppression—The Great Challenge 

The overwhelming obstacle to success in any kind of transplant therapy for diabetes is the body’s own immune response—the same basic response that provokes type 1 disease in the first place. Even in perfectly healthy people, the introduction of a “foreign” body or substance prompts our immune system to reject the invader, a problem all transplant surgeries must overcome.

An array of powerful immune-suppressing drugs has been developed to counter this natural reaction of the body. In the case of both pancreas and infused-islet transplants, these drugs do work to a greater or lesser extent, allowing the new islets to go on doing their job of producing insulin. People who received pancreas transplants as long ago as the 1980s still have functioning islets, and the drugs also extend the effective life of infused islets.

But for most type 1 diabetics, and those working on cures, using immune-suppressing drugs is not a satisfactory long-term solution. The drugs are hugely expensive and highly toxic by their very nature, with potentially risky side effects. They must be used rigorously and indefinitely for the life of the transplant. And because they act very broadly, they can sometimes injure the new islets and reduce the benefits of transplantation.

Work on improving immune-suppressing drugs—a major research area in itself—is progressing. But it’s not hard to see that a better approach would be to erase the need for them.

“For any type of transplantation procedure, a balance is sought between efficacy and toxicity.”

—Jonathan R. T. Lakey and coauthors of the
landmark paper on the Edmonton Protocol,
published in the New England Journal of Medicine, 2000

Encapsulating Islets

To protect the islets and beta cells from autoimmune attacks, researchers are exploring several ways to “encapsulate” or wall off islets before they are transplanted. Some kind of semi-permeable barrier surrounds the islets, excluding large molecules (like the immune system’s soldiers) yet allowing oxygen and other nutrients to reach the beta cells and insulin to be released.

Islet encapsulation and the bioartificial pancreas are different ways to describe the same line of research. There are two main approaches: macro- and microencapsulation; each has its pros and cons. Within these categories, the protective devices take various forms: coatings, capsules, hollow fibers, and sheets. Because macroencapsulated islets are more stable and easier to retrieve if needed, the Islet Sheet Project supported by Hanuman is pursuing this track.

Takeaways

  • Both whole-pancreas and islet transplants have been used to treat T1D for many years, but with limited success.
  • Transplanting islets is preferred because it doesn’t involve major surgery. Drawbacks include limited supply of islets and the need for toxic immune-suppressing drugs.
  • One way to protect transplanted islets from the destructive immune response of type 1 is to “encapsulate” them. This is the basis of the Islet Sheet Project.