Islet Cell Transplantation: Can It Facilitate Insulin Independence?

By Jessica Kaylor, BA, and John S. Steinberg, DPM

   After the islet cells are collected and transplanted into a recipient, the patient’s immune system often attacks the foreign islet cells. Researchers have developed a method using contrast agents and magnetic resonance imaging (MRI) to assess the degree of rejection of the transplanted cells, and determine the success of the transplant.5 Beta cells of the pancreas, which are responsible for the production of insulin, are particularly at risk for attack by the immune system as well as by infectious agents or toxic materials involved in diabetes mellitus type I.6 As a result, one would use immunosuppressant drugs in tandem with islet cell transplantation to minimize rejection of foreign cell material which, in turn, hampers the patient’s ability to fight infection and disease.

   Another unfortunate and ironic result of immunosuppressant therapy is the decreased function of the recipient’s own limited supply of islet cells. Radical pharmaceutical developments are needed to create immunosuppressant drugs that act only to assist in the acceptance of donor islet cells instead of suppressing the recipient’s entire immune system.

   Researchers have utilized gene transfection, or the injection of foreign DNA into a cell to alter its properties, to strengthen beta cells’ defense from an attack on the immune system.6 We need a better clinical understanding of how cells protect themselves from attack by the immune system before this technique can significantly increase the effectiveness of beta cell replacement.6 An additional concern is the fact that immunosuppressive therapy negatively impacts renal function. Accordingly, this therapy would be limited to those with healthy kidneys.

A Closer Look At The Edmonton Protocol

Islet cell transplantation can be categorized into two different eras: before and after the Edmonton Protocol. The protocol was developed in the 1990s and the first patient was treated under its statutes in 1999. This special course of treatment introduced pivotal changes to the world of islet cell transplantation. Total pancreatic transplantation was the preferred surgical procedure for long-term glucose control before the Edmonton Protocol revolutionized islet cell transplantation.2 Insulin independence in patients with type 1 diabetes one year after islet cell transplantation rose from 20 percent to nearly 80 percent after the Edmonton Protocol became the standard of care.3,7

   Advancements in how islets are isolated, purified and extracted from donors, using a mixture of enzymes called Liberase, factor into the success of the protocol. Better adjunctive immunosuppressive drugs, such as sirolimus and tacrolimus, and the monoclonal antibody drug daclizumab (Zenapax, Roche U.S. Pharmaceuticals), also contribute to the protocol’s success.2,8 Additionally, changes in the transportation of the donor pancreatic islets as well as the amount of cells transplanted into the recipient also contribute to the increased insulin independence rates.2,8

   However, even with the advances involved in the Edmonton Protocol, problems still exist with successful, long-term islet cell transplantation. Some researchers question the efficacy of sirolimus, a drug of choice of the protocol, as an effective immunosuppressant for islet cell transplantation as the drug may potentially impede the growth of pancreatic ductal cells and minimize the secretion of insulin.9 Furthermore, the long-term outcome of islet cell transplantation is still quite dismal. In 2006, one study claimed only 10 percent of transplanted patients were insulin independent after five years.3 Although there is hope with recent advances, the outcome of islet transplantation is still not a permanent solution for type 1 diabetes.

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