Biomedical Frontiers: Fall 1997, Vol.4, No.2
Diabetes Research
Pancreatic Islet Transplants Set to Begin

Researchers isolating pancreatic islets.

After nearly two decades of research, studies of pancreatic islet cell transplantations in humans are set to begin at CPMC this spring. A team of researchers, led by Dr. Mark A. Hardy, the Hugh Auchincloss Professor of Surgery and director of transplantation, will transplant ultraviolet B irradiated pancreatic islets into patients with Type I diabetes who are either undergoing a kidney transplant or have already received one and are doing well.

Pancreatic islet transplantation has been performed on humans before, but its effectiveness is limited by both rejection and autoimmune destruction of foreign cells. To overcome these problems, Dr. Hardy will first treat the cells with ultraviolet B (UVB) radiation, which paralyzes the antigen-presenting cells. UVB also disturbs the normal function of T cells, which are important in initiating islet cell destruction. "UVB irradiation alters the cells so they are not as readily rejected and are better tolerated, especially when the treatment is combined with a brief period of immunosuppression," says Dr. Hardy.

Pancreatic islets.

By injecting the islets into patients also undergoing kidney transplants, the researchers will be better able to identify any signs of rejection: If a kidney rejection develops, it probably also means that the islets are being rejected. Treating the kidney rejection--the symptoms of which are easier to spot at an early stage--also treats the islet rejection.

The researchers also will transplant pancreatic islets into people with diabetes who have already undergone kidney transplants and have been stable for six months to one year. "We want to make certain that there are no adverse effects on the kidneys," says Dr. Hardy. "This has already been shown by others when pancreatic transplants are done together with kidneys, but only tentatively when islets follow kidney transplants."

To help satisfy the demand for donor pancreatic islets, Dr. Hardy is working with Dr. Keith Reemtsma and others to genetically modify pancreatic islet cells from pigs and fish.

By purifying HLA molecules from islet cells, Dr. Paul Harris, associate professor of clinical pathology, has identified some of the autoantigens relevant to diabetes (Diabetes, December 1996). "We have to show that diabetic patients react to this antigen," says Dr. Harris. "But we now know exactly what T cells may 'see' and can eventually make peptide analogs to turn off, divert, or tolerate T cells." Above, autoantigens, drawn from the cell interior and presented at the cell surface with the help of HLA molecules, may speed islet destruction.