What to Expect From an Islet Cell Transplant

Pancreatic islet cell transplantation is an experimental procedure for treating type 1 diabetes. The goal of this procedure is to make it possible for people with this autoimmune disease to stop taking insulin—a vital hormone produced by the pancreas that controls the levels of glucose (sugar) in blood. People with type 1 diabetes aren't able to generate insulin on their own, putting them at risk for serious and potentially fatal complications ranging from damage to nerves (neuropathy) or eyes (retinopathy) to heart disease.

Because islet cell transplantation—sometimes called allotransplantation or beta-cell transplantation—is still being studied, it is performed in the United States only in clinical trials sanctioned by the U.S. Food and Drug Administration (FDA). According to the Collaborative Islet Transplantation Registry, 1,089 people throughout the world have received islet transplants for treating type 1 diabetes.

Reasons for an Islet Cell Transplant

Pancreatic islets, also called islets of Langerhans, are one of several types of groups of cells in the pancreas—the organ that helps the body break down and use food. The beta cells that exist within the islets are responsible for producing insulin.

Insulin is vital to life. Without it, glucose quickly builds up in the blood to potentially fatal levels while the cells in the body are starved of the energy they need to function properly.

In type 1 diabetes, the immune system destroys the beta cells. It isn't known why this happens, but without functioning beta-cells the body isn't able to produce its own insulin. So for people with the condition, daily injections of supplemental insulin or the use of an insulin pump is the cornerstone of treatment.

Giving oneself shots or having to maintain a medical device can be a challenge, however, which is why islet cell transplantation could be an appealing alternative for some people.

Doctors consider people for islet transplantation if the possible benefits, such as being better able to reach blood glucose targets without problems, outweigh the risks, including the possible side effects of immunosuppressants. Recipients must take Immunosuppressant medicines to prevent the immune system from attacking and destroying the transplanted islets.

People with type 1 diabetes who are planning to have or have had a kidney transplant to treat kidney failure may also be candidates for islet transplantation, which can be performed either at the same time or after a kidney transplant.

Islet cell transplantation is not indicated for people with type 2 diabetes because they require more islet cells to achieve insulin independence than it is currently possible to isolate from a pancreas.

Donor Recipient Selection Process

In general, candidates for islet cell transplantation include people with type 1 diabetes who:

• Are 18 to 65 years old
• Have blood glucose levels that are difficult to manage
• Have poorly controlled type 1 diabetes, including episodes of severe hypoglycemia and hypoglycemia unawareness
• Might require or already have received a kidney transplant
• Are not currently pregnant, in the process of trying to become pregnant, or nursing a baby, due to the risks of immunosuppressive drugs on a baby (in utero or via breast milk); women of childbearing age must agree to use contraception

Because islet cell transplants are currently performed solely in clinical trials, recipient criteria can vary. Other things that may be taken into consideration are the person's body mass index (BMI), with a required BMI of 28 or lower; status of liver and kidney function; and whether infection, cancer, hepatitis, or HIV is present.

When someone signs up for a clinical trial, they will first be screened to see if they meet the criteria for inclusion. If they qualify, they will be put on a waiting list until an appropriate pancreas is obtained.

Types of Donors

Islet cells are retrieved from the pancreas of a deceased person who chose to donate their organs. Unfortunately, a major obstacle to the widespread use of pancreatic islet cell transplantation is a shortage of islet cells from donors.

The National Institute for Diabetes and Digestive and Kidney Diseases reports that 1,315 pancreata were recovered from deceased donors in 2017. Many are not suitable for islet isolation, leaving only a small number available for use each year. Some donor islets may also be damaged or destroyed during the transplant process.

Furthermore, it is not uncommon for a patient to require more than one transplant over time, meaning that one person may ultimately require islets from more than one pancreas.

To compensate for this shortage, researchers are studying ways to transplant islets from other sources, such as pigs, and working on creating new islets from human stem cells.

Before Surgery

Prior to receiving an islet transplant, it is necessary to undergo a standard pre-operative evaluation, including blood tests, tests of the heart and lungs, and an oral glucose tolerance test.

Surgical Process

The islet transplant process itself is a relatively simple, non-surgical outpatient procedure. Since this procedure is done on a clinical research basis, however, patients often have to stay in the hospital for monitoring.

Beta cells from the pancreas of a deceased donor are purified and processed, and then transferred to the patient via infusion. During a single transplant, patients typically receive two infusions containing an average of 400,000 to 500,000 islets each. The procedure takes about an hour per infusion.

This is usually performed by an interventional radiologist (a doctor who specializes in medical imaging). Using X-rays and ultrasound imaging for guidance, they will thread a catheter (a thin plastic tube) through a small incision in the upper stomach into the portal vein—a major vein that supplies blood to the liver.

Once the catheter is in position, the prepared islet cells are slowly pushed through it. Allotransplantation can be done using local anesthesia and a sedative. General anesthesia, which is riskier, is rarely necessary.

Complications

The transplant procedure can increase the risk of bleeding and blood clots. It can also have complications that will require open surgery (intraperitoneal bleeding requiring transfusion or laparotomy).

There is also a chance that the transplanted cells may not work well or at all. In addition, all of the cells may not work right away and may take time to start functioning properly. Therefore, recipients may need to take insulin until the cells begin working properly.

It is also possible that donor-specific antibodies will develop. In this case, the recipient's body starts attacking the donor cells.

Another potential consequence of islet transplantation is the development of multiple donor-specific antibodies. Because islets are obtained from multiple donors, islet transplant recipients are exposed to multiple human leukocyte antigen mismatches. Multiple mismatches result in multiple antibody formation, which may prevent the patient from undergoing future transplantation (islet, kidney, pancreas) due to a decreased likelihood of finding a compatible graft.

Adverse events related to immunosuppression (neutropenia, elevated liver function tests, or kidney failure) may also rarely occur.

After Surgery

Following surgery, new blood vessels form and connect the islets with the blood vessels of the recipient and begin to make and release insulin, with two key benefits:

• Normalization of glucose levels without dependence on insulin injections, or at least a reduction in the amount of insulin needed
• Reversal of hypoglycemia unawareness—a loss of the ability to sense symptoms of dangerously low blood sugar (typically, 70 mg/dL or less), such as sweating, shaking, increased heartbeat, anxiety, or hunger, and treat it accordingly

Preventing Rejection

In order to receive pancreatic islets from another person, the recipient will need to be on immunosuppressive medications to prevent rejection of the cells.

Some of these, such as corticosteroids, can complicate diabetes by increasing insulin resistance over time and causing a rise in blood sugars. Other types of immunosuppressants may reduce the ability of beta cells to release insulin. Additionally, immunosuppressants inhibit the immune system's ability to fight infection and may cause liver enzyme elevation and potential kidney failure.

At the same time, there is also a risk that, despite being suppressed by medication, the autoimmune response that initially destroyed a person's native cells and caused type 1 diabetes in the first place might be triggered again, this time attacking and destroying the newly transplanted donor cells.

Prognosis

A phase 3 clinical trial conducted by the National Institutes of Health Clinical Islet Transplantation Consortium found that a year after islet cell transplantation, nine out of 10 recipients had an A1C level (a measure of average blood glucose levels over two or three months) below 7%, had no episodes of severe hypoglycemia, and did not need to take insulin. Two years after transplantation, seven out of 10 recipients had an A1C level of less than 7% and did not have episodes of severe hypoglycemia, and about four out of 10 did not need insulin.

The transplant recipients also had improvements in quality of life and overall health—including those who still needed to take insulin.

A Word From Verywell

Research on islet cell transplantation is currently focused on being able to collect enough islet cells by using cells from other sources, including fetal tissue and animals. Scientists are also attempting to grow human islet cells in the laboratory. And, while advances have been made in developing new and better anti-rejection drugs, more work needs to be done in this area.

Clearly, it will be some time before islet cell transplantation becomes a routine treatment for type 1 diabetes. But the concept is intriguing and worth knowing about if you or a loved one has this form of the disease. Information on joining a clinical trial on islet transplantation can be found at ClinicalTrials.gov.