Islet Transplantation F.A.Q.s

What are islet cells?
Islet cells are specialized cells found within the pancreas. They produce several hormones including insulin, glucagon and somatostatin. Insulin is the most important of these, as it keeps blood glucose levels within a normal range by allowing the glucose (a form of sugar that comes from food) to enter cells where it gets converted into energy for the body. These islet cells are clustered (scattered among other cells in the pancreas) in formations called “Islets of Langerhans,” so they are often referred to as islet cells or pancreatic beta cells. In people with type 1 diabetes, these cells are attacked and destroyed by the body’s own immune system.

Below: Islets of the human pancreas, stained with dithizone immediately after isolation.

What is islet transplantation?
One of the most promising potential treatments for type 1 diabetes is the possibility of transplanting healthy insulin-producing islet cells from donor pancreases into patients whose islet cells have been destroyed. If successful, the transplant could restore their ability to produce insulin and cure their diabetes.

What steps are involved in an islet transplant?
Islet transplantation is a complex process:

• First, a pancreas is harvested from an organ donor cadaver, which is a step performed by an organ bank. 
• Within eight hours, the pancreas is transported to a laboratory where the islet cells are isolated. Isolation is the most difficult part of islet transplantation. A highly skilled team of four to five people must work continuously for 10-14 hours to complete the isolation. 
• Then, if the quality and quantity of the isolated islets is satisfactory, a patient is called to the hospital to receive a transplant. 
• The transplantation itself is relatively simple. The patient receives local anesthesia and a light sedative, and then a small tube is inserted into the portal vein through a needle just below the rib cage on the right side of the abdomen.
• The islets are infused into the liver, settling in the capillaries of the portal in the liver (not in the pancreas itself). This procedure takes about one to two hours, and the patient is generally sent home the next day. 
• Following transplant, the patient must take three immunosuppressive medications to protect the islets from rejection.

What is the current status of islet transplants at Joslin?
Since November 2001, 18 patients have been transplanted with islets from Joslin’s Islet Isolation Core at Harvard Medical School. Most of these patients also received a kidney transplant. Three of these patients were transplanted with their own islets after their pancreas was removed due to severe pancreatitis (a painful, chronic inflammation of pancreatic acinar cells). The islet core laboratory at Joslin serves patients at three main hospitals affiliated with Harvard Medical School: Massachusetts General Hospital, Brigham and Woman’s Hospital and Beth Israel Deaconess Medical Center.

What is the Edmonton Protocol and what is its impact on transplantation?
The Edmonton Protocol is a procedure developed in Canada, which began in 2000. The Edmonton team applied new methods for isolating and transplanting islets that have drastically improved the success rate of the procedure. They began using new types of immunosuppressive medications, which proved to be gentler to the islets. They also began transplanting the islets sooner—at the end of the isolation process—without taking time for the cells to culture.

To date, out of 75 patients who received transplants as part of the Edmonton study, some have achieved insulin independence (successful transplants) up to five years. The Edmonton study clearly demonstrated that islet transplantation could be successful. Since then, tremendous effort has been put into other islet studies. Joslin participated in a multicenter study called the Immune Tolerance Network (ITN), which reproduced the success of islet transplantation in a number of other centers. Today more than 34 centers around the world are transplanting islets. 

How successful are islet transplants?
Overall, the success rate following an islet transplant is 80 percent after one year and 70 percent after two years. Generally, two or three transplants are necessary to achieve long-term insulin independence. At Joslin, the longest insulin independency achieved has been 22 months after two transplants in one patient.

This rate of success demonstrates the progress of islet transplantation within the past five years—before the year 2000 there was no period of insulin independence observed following islet transplantation. Now, scientists working in the islet field have a much better understanding of factors that could further improve the long-term success of the procedure. One of the most recent reports from the University of Minnesota showed that in some cases insulin independency could be achieved for up to 15 months after transplantation of islets from a single pancreas.

Am I a candidate for an islet transplant?
Currently islet transplantation is considered experimental—it is not a routine treatment for diabetes and the cost of the procedure and follow-up care is not reimbursable through insurance. Islet transplantation is primarily reserved for patients with severely debilitating diabetes and those who have had no success with any of the conventional treatment methods—especially those who have frequent and severe episodes of low blood glucose (hypoglycemia), those who lack low glucose awareness and those with a very poor quality of life.

These patients receive the most benefit from islet transplantation even if they do not become insulin independent after transplantation. Improvements in blood glucose control and a reduction of hypoglycemic episodes can drastically improve their quality of life. Patients who are undergoing kidney transplantation and are already going to receive immunosuppressive therapy may also be candidates. In these cases, physicians sometimes change their immunosuppressive protocol to also accommodate islet transplantation.

Is transplantation an option for children?
To date, there has not been enough information provided to support the safety of islet transplantation in the pediatric population. Currently the minimum age of eligibility for the procedure is 18. There are several potential dangers of transplantation, including side effects from immunosuppressive medications, such as infertility and an increased risk of developing cancer in the future.

Can my relative donate islet cells for a living donor transplant?
Not at this time. Currently the only approved source is the organ donation program. Studies are underway to explore the potential of living donor transplants in the future. However, because living donor transplants require removal of half of the donor’s pancreas, there is concern that the donor may develop diabetes in the years following transplant. Also, the operation required to obtain the donor pancreas is not something to be taken lightly.

What are the challenges of islet transplantation?
There are two main challenges:

• There is a limited supply of islets available for transplant. The number of donated organs used for islet transplantation is much lower than the current number of people with diabetes—not to mention those who are newly diagnosed each day. Thus even under the best conditions, transplantation cannot be made available to the majority of the population with type 1 diabetes. 
• Also, transplanted islets are subject to the same autoimmune attack that initially triggered type 1 diabetes. Typically, patients must take several different immunosuppressive medications to prevent the rejection of the transplanted cells and maintain insulin independence. When taking these medications, patients are at an increased risk for illness and infection and may experience other side effects. 

What are the most recent developments in islet research at Joslin?
Joslin’s Section on Islet Transplantation and Cell Biology focuses on clinical as well as experimental islet transplantation. As mentioned above, there are two main limitations for clinical islet transplantation. Scientists in the islet transplantation research team search for new ways to overcome both of these problems.

Current research focuses on one possibility: microencapsulation of pig islets. The method involves isolation of islets from adult or very young pigs. Pigs are an excellent species to study because until relatively recently, pig insulin was widely used before human insulin was available. Pig tissue is readily available and pig islets can be successfully isolated and can respond to blood glucose in a similar way to human islets. The isolated pig islets are covered with a natural material called alginate (a derivative of sea weed), so that the recipient’s immune system will not detect the transplanted islets and not reject the material used to cover them. The encapsulation material, alginate, is shown to be non-harmful to the recipient. The microcapsules (with a diameter of 0.8mm -1mm) are transplanted into the abdominal cavity of the recipient mouse or rat.

The studies of mouse models show that blood glucose can be maintained in normal range for up to 200 days after transplantation without the use of immunosuppressive drugs. Current efforts are underway to advance the experiments to larger animal models.

Below: The concept of encapsulation – I:islet; IgG: Antibody, Immunoglobulin-G; IgM: Antibody, Immunoglobulin-M.

Below: Encapsulated pig islets stained with dithizone dye. Red shows insulin.

Is Joslin recruiting patients for transplants or islet research?
Not at this time; however, when a new clinical trial begins, a call for patient volunteers is posted on our Web site. You may wish to check back periodically to find out if there are any new studies that may be appropriate for you.

What if I still have questions?
To e-mail a specific question to a member of our islet isolation team, click here.

For more information, please visit the following links:
Islet Transplantation and Cell Biology Research Section
Islet Core at JDRF Center on Immunological Tolerance in Type-1 Diabetes
Intro to Islet Transplantation and Cell Biology