UA Researcher Awarded Grant for Islet Cell Transplant Work

The work focuses on maximizing the effectiveness in diabetic patients of an implantable device containing insulin-producing islet cells.

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Dr. Klearchos Papas, professor of surgery at the University of Arizona, has been awarded more than $100,000 by JDRF for research that could help pave the way for new and improved therapies for patients with Type 1 diabetes. JDRF is the world's largest charitable funder of Type 1 diabetes research.

Papas's work focuses on maximizing the effectiveness of an implantable device containing insulin-producing islet cells, which could serve as an alternative to islet cell transplantation in the liver.

In people with Type 1 diabetes, the body's pancreas produces little or no insulin, a hormone that helps the body use or store the blood glucose it gets from food. While Type 1 diabetes may be diagnosed at any age, its onset most often occurs during childhood or young adulthood. JDRF estimates that as many as 3 million Americans live with Type 1 diabetes.

Most patients with Type 1 diabetes require routine insulin injections, but in some patients, the injections aren't enough to keep diabetes under control. In those cases, surgical intervention may become necessary.

Apart from a full pancreas transplant, one modern surgical intervention for Type 1 diabetes is islet cell transplantation, a minimally invasive procedure in which insulin-producing islet cells from a donor pancreas are infused into a diabetic patient's liver, where they begin producing the insulin the body needs.

While the procedure, which is still considered experimental in the U.S., can be effective, it is not without challenges, says Papas, scientific director of the UA's Institute for Cellular Transplantation.

For one, supply of human donor pancreases is limited, and to be successful, an islet cell transplant procedure often require cells from two to three separate donor pancreases, since not all cells survive the process that extracts them from the donor organ and purifies them for transplant, and up to 40 percent of the cells immediately die post-transplant.

An additional concern is that patients who undergo islet cell transplantation must take immunosuppressant drugs for the rest of their lives to keep the body from rejecting the donor cells. Those drugs can be very taxing on the body, and for that reason, the procedure is done on patients who absolutely need it, and it is rarely done in children, Papas said.

As an alternative to islet cell transplantation into the liver, the medical community has been exploring the possibility of implanting patients with islet cells contained within a specially engineered immunoisolation device, which has semipermeable membranes designed to protect the cells from attack by the immune system but allow the insulin they produce to pass through to the body. The device, implantable just beneath the skin, could eliminate the need for powerful anti-rejection drugs, make islet cells available to a larger population of diabetics in need and provide a safer option for children, Papas said.

The device also could potentially allow for effective use of islet cells from sources other than a human pancreas, such as porcine islets – islet cells from pigs, which the human body would reject if infused into the liver, even with immunosuppressant drugs – or human stem cells, Papas said, thus addressing current limitations on donor pancreas availability.

Although implantable devices have proven successful in reversing diabetes in animal models, maximizing their effectiveness in humans poses unique challenges, mostly due to the large volume of islet cells the human body requires, Papas says.

Devices currently being tested, which are about the size of a postage stamp, can successfully accommodate only about 500 islet cells, while the human body requires closer to 500,000. Therefore, to be effective in a human, the device would have to be much larger, approximately the size of a 20- or 30-inch television screen, Papas said. That makes for an impractical solution, unless researchers can find a way to make a smaller device more effective, which is what Papas aims to do.

The reason so few cells can survive within a small device is because they require oxygen to live and function properly; if too many cells are crammed into one area, they will begin to suffocate, Papas said.

To address that problem, Papas and his colleagues, with funding from JDRF, will test the effectiveness of a battery-operated electrochemical oxygen generator, about the size of a stack of dimes, which would provide the implanted device, and the cells within it, with a continual oxygen supply, providing for survival of a much greater number of cells in a single, small device.

"The key critical limitation that we're addressing is oxygen supply to an implantable immune-isolating device," Papas said. "The key outcome would be that we would minimize the size of the device required to reverse diabetes in a human from that of a 20- or 30-inch TV screen to a large postage-stamp-sized device, while maintaining the ability of the cells to survive and function."

If the technique proves successful, the goal will be to develop an implantable version of the oxygen generator that will work hand-in-hand with the immunoisolation device.

If successful, the technology might also prove useful in cell therapies for the treatment of other diseases, Papas said.

"This could have the potential to treat millions of people with diabetes, and it's conceivable that it would enable other applications as well."

Dr. Klearchos Papas
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Papas is studying how a small oxygen generator might help significantly reduce size requirements for an implantable device containing insulin-producing islet cells for diabetic patients in need.
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