Pancreas Transplants

Printer Friendly |

E-mail This Page | Text Size

Last Updated: Monday, February 13, 2006

Q: "Would you tell me the progress on pancreas transplants? Can just a portion of the pancreas be transplanted, or do they have to use the entire gland?"

A: Currently, research is focusing on transplanting just the islet cells of the pancreas, which are the specific cells that produce insulin. Keep in mind that transplants work only for people with type 1 diabetes. The main defect in type 2 diabetes is related to insulin resistance--the body's inability to use insulin properly.

While I will provide you with an overview of the progress, I would encourage you to read more information in the resources provided below, as well as to receive updates by signing up for e-newsletters from these resources.

We've come a long way…

Over 3500 years ago: the syndrome of diabetes was described, but not defined as "diabetes" until the 1st century by Arataeus.
1500's: Paracelsus performed the first chemical experiments with diabetes (including tasting the urine).
1893: An English surgeon, Watson Williams, attempted the first transplantation of pancreatic fragments from a sheep to a 15-year old boy. This was before it had been established that the pancreas was even capable of producing a "sugar-destroying substance" and it also preceded the discovery of insulin by almost 30 years.
1921: Insulin was discovered.
1929: A doctor in Italy preserved islets one month after transplanting pancreatic fragments.
1966: First pancreas transplant in humans.
1969: Considered, the "real father of islet transplantation", Paul E. Lacy was the first to describe a method of isolating islets, and performing a successful islet transplantation in rodents a few years later.
2000: Researchers in Canada reported significant success using a different combination of anti-rejection drugs in a new procedure, now termed the Edmonton Protocol.
2002: 80% of the 190 people worldwide who have had islet cell transplants with this new technique are remaining insulin-free 1 year later; and those who still require some insulin have considerably improved blood glucose control.
2004: Over 300 patients have received islet infusions and have enjoyed insulin independence or dramatically improved quality of life.
2006: Results were reported from The International Trial of the Edmonton Protocol for Islet Transplantation. (See further below).

Pancreas Transplants

While some organs in the body, such as hearts or kidneys, are often transplanted without problems, pancreas transplants are not as successful. One to two people in 10 die within a year of getting their transplant. Despite the use of anti-rejection drugs, approximately half of all pancreas transplants are rejected. While the positive aspects of a transplant would be that the diabetes is "gone", and diabetes complications often stop progressing, the reality is that there are simply not enough pancreases to supply all the people with type 1 diabetes.

Other problems:
- Anti-rejection drugs: The body treats a transplanted pancreas as foreign, and will reject it without the use of anti-rejection drugs-also called immunosuppressive drugs. These drugs are hard on the body, increasing the risk of infections, damaging the kidneys, and increasing the risk of some cancers, among other problems. Due to these strong side effects, pancreas transplants are rarely performed unless the person has had a kidney transplant, and is already required to be on anti-rejection drugs.
- Other complications: Because other diabetes complications are often present at the time of the kidney/pancreas transplant, the person has an increased risk of problems from vascular complications.

Islet Cell Transplants

Islets are the clusters of cells in the pancreas that make insulin; only 1-2% of the pancreas is made up of islet cells. In this procedure, special enzymes are used to separate the islets from the pancreas of a deceased donor; then these islets are placed in a tube and injected into the liver. These cells attach to new blood vessels and begin releasing insulin. This type of procedure is considered easier and safer than the major surgery of a pancreas transplant. In fact, eventually this could be performed as an out-patient procedure. Challenging issues involve:

Immunosuppression: The body still recognizes these islets as foreign, so the person must still take anti-rejection drugs. But other options being investigated include:
Developing safer, less toxic anti-rejection drugs.
Encapsulating the islet cells, allowing the important nutrients to pass through the membrane, but blocking attack of the rejection cells (think of Gortex fabric, that allows a runner's perspiration to escape through the fabric, but prevents rain from getting through to the person's skin.

Islet Cell Procurement

For every person needing an islet cell transplant, two donor organs were generally required because one organ could not provide an adequate number of islet cells. These islets are extremely fragile, and transplantation needed to occur immediately. Recent progress includes:

Improved techniques to isolate the islets from the pancreas, and reduce damage to the islets, and hopefully only require one donor organ per person.
Bathing the islets in a special fluid prior to transplantation has improved the success, as well as allowed islets to be shipped to other centers to be transplanted.
Using embryonic stem cells would be an alternative source of islet cells. Stem cells are capable of growing into other types of cells, which could potentially provide unlimited supplies of islet cells. Research continues on this, but there are challenges and ethical controversies involved with what is termed "therapeutic cloning."

So where are we now?

9 Medical centers in North America and Europe expanded on the success of the Edmonton Protocol with the goal of transplanting 40 additional patients in a 7-year study conducted by the Immune Tolerance Network (ITN)-an international consortium of over 80 leading physicians and scientists from over 40 institutions in 9 countries world-wide, and organized and supported by funds from JDRF and NIH and headquartered at the University of California San Francisco. The goals were to validate the protocol, establish a network of well trained clinical centers, and to provide a baseline measure for all future trials. They sought to answer questions regarding: safety, effectiveness, and the ability to sustain success.

The nine clinical centers participating in the trial were: University of Alberta (Canada); University of Miami; University of Minnesota; Harvard Medical School; Pacific Northwest Research Institute; Washington University St. Louis; Justis-Liebig University (Germany); University of Milan (Italy); and University Hospital of Geneva (Switzerland).

Results from the study were reported in September, 2006. The primary end point was defined as insulin independencewith adequate glycemic control 1 year after the final transplantation.
- Of the 36 subjects, 16 (44%) met the primary end point,10 (28%) had partial function, and 10 (28%) had complete graftloss 1 year after the final transplantation.
- A total of 21 subjects(58%) attained insulin independence with good glycemic controlat any point throughout the trial. Of these subjects, 16 (76%)required insulin again at 2 years; 5 of the 16 subjects whoreached the primary end point (31%) remained insulin-independentat 2 years.
- Conclusion: Islet cell transplants can restore the body's ability to produce insulin and improve diabetes control. However, permanent independence from requiring injectable insulin has not been sustainable. Despite this, having some islet function even without insulin independence provides both protection from severe hypoglycemia and improved levels of diabetes control.

As Dr. Camillo Ricordi, Scientific Director of the Diabetes Research Institute at the University of Miami, and recipient of the 2002 Outstanding Scientific Achievement Award, stated, "We will get this job done, and this is not a prediction. It is a promise!"

Pancreas Transplants

We've come a long way…

Pancreas Transplants

Islet Cell Transplants

Islet Cell Procurement

So where are we now?

Related Questions

Related Links

Ask a Question

Question Categories