Naturally Occurring Protein Protects Human Islet Cells from Death
Miami, FL (August 27, 2003) -- Scientists from the Diabetes Research Institute (DRI) have found that a common protein the body uses to produce red blood cells may also prevent the premature death of the insulin-producing cells (islets) typically destroyed by the immune system in type 1 diabetes.
The researchers first discovered receptors for the naturally occurring protein erythropoietin (EPO) on the surface of the pancreatic islets of several species, including man’s, then went on to demonstrate that adding EPO to islet cells in culture prevented their death without affecting the cells’ ability to secrete insulin.
The results of these novel series of experiments will be presented at the XIX International Congress of the Transplantation Society in Miami and published in Transplantation.
The transplantation of islet cells as a way to treat type 1 diabetes has been rapidly gaining ground on the more established but higher risk whole pancreas transplant, with new international data showing that as many as 80 percent of patients remain insulin free one year after receiving infusions of the insulin-producing cells.
Most of these clinical successes, however, require multiple infusions of islet cells, since one of the major obstacles preventing this promising therapy from more widespread application is the poor survival of isolated islets once they’ve been transplanted.
“The programmed cell death of these cells is an underlying mechanism that contributes to as much as 60% of pancreatic islet loss in the transplant setting,” explains principal investigator Elizabeth Fenjves, Ph.D., Research Assistant Professor of Medicine and Pediatrics, and Director of Gene Therapy at the DRI.
“If we could protect the cells from signals that trigger their death during isolation, culture and transplantation, we would be on the right track to a much more efficient use of these very fragile, life-saving cells.”
Using standard molecular biology techniques that included RT-PCR, immuno-histology and Western Blot testing, Dr. Fenjves’ team began by demonstrating that mouse, non-human primate and human islets all expressed the receptor for EPO, a novel and unexpected finding in and of itself.
In the body, circulating EPO binds to EPO receptors found on the surface of certain progenitor cells in the blood lineage and gives rise to the body’s red blood cells through a mechanism that is still not completely understood. This is the first time that EPO, a protein known to protect several cell types from the toxicity of low oxygen levels and other biological stressors, has been associated with a protective role for islets.
Fenjves and colleagues were able to determine that EPO receptors were indeed located throughout the cluster of islet cells, including the beta cells specifically known for their insulin-secreting abilities.
Having found EPO receptors, the DRI team proceeded to determine what effect EPO might have on islet survival by adding the protein to islet culture medium and subsequently measuring cell death rates in presence of different known chemical triggers for cell death. They found that preconditioning the culture media with EPO protected the islets from chemically-induced destruction in a dose-dependent manner, and without adversely affecting the ability of the islet cells to secrete insulin.
“We’ve been able to show that we can protect islets from known triggers of cell death using an FDA-approved, non-toxic additive, and that is very exciting,” adds Dr. Fenjves. “We are already in the next phase of evaluating this intervention in a more clinically relevant model, since we need to determine whether we can carry over the protection we see in the lab into the transplant setting.”
Mitra Zehtab, MD, MBA