U tests experimental diabetes transplant treatment

Jan. 16--Researchers at the University of Minnesota have studied everything from human organ donors to specially grown pigs as sources of insulin-producing islet cells for people with type 1 diabetes who lack them.

Now they are testing the transplant of islets from a new source -- embryonic stem cells.

The university earlier this fall became the third U.S. academic institution to transplant an islet cell product made by California-based ViaCyte in patients with severe and poorly controlled diabetes.

A stem cell solution to producing islets could be a significant step in the treatment of type 1 diabetes, said Dr. Melena Bellin, the university researcher leading the local arm of the ViaCyte study. While islets can be transplanted from deceased organ donors, that supply is limited and unpredictable.

"Really, to overcome that barrier, you have to find some sort of renewable source of islets," she said.

Insulin is a hormone in the pancreas that regulates the body's storage and use of sugar. Type 1 diabetes is diagnosed when people lack the islets to produce insulin.

New trial

Gregory Romero was the second to sign up for the trial. The 43-year-old web developer has resented his type 1 diabetes but managed it through insulin injections.

In recent years he has become less sensitive to fluctuations in his blood sugar, which has resulted in blackouts. Once, he awoke after falling down stairs. Another time, he couldn't walk and had to crawl out of his house to meet paramedics.

Having a chance at a treatment that could stabilize his blood sugar felt like "winning the lottery," said Romero, whose father suffered a diabetic coma that left him mentally handicapped.

"It's not just for my sake, but for everybody out there suffering from this disease," Romero said. "If this thing is successful, they're going to be able to help a lot of people. ... There are some selfish reasons, too. I hate this disease."

Transplant researchers have always faced two challenges -- how to produce enough islet cells for a sustainable supply of insulin in people with type 1 diabetes, and how to prevent the immune system from attacking the transplanted cells.

Transplant pioneer

The university pioneered transplants of islets from organ donors; the world's first clinical islet transplant was performed in Minneapolis by Dr. David Sutherland in 1974. Continued progress has resulted in the university applying to the U.S. Food and Drug Administration for approval of its technique for procuring and transplanting donor islets.

The U's Dr. Bernard Hering also has studied "xenotransplantation" of islets from pigs, which could be grown to mimic patients' immune systems and reduce the odds of transplant rejection.

ViaCyte's approach is to coax stem cells, which came from a human embryo that wasn't used for in vitro fertilization, to produce immature pancreatic cells. They are then placed in pouches that are implanted in the arms and lower backs of diabetic patients, where the cells then produce islets that release insulin into the bloodstream.

The company's first product was a tightly closed pouch designed to prevent the recipients' immune cells from entering and attacking the transplanted pancreatic cells. That would prevent patients from needing drugs to suppress their immune systems, which can be potent and cause their own severe side effects.

Bellin said this protection seems to cut the donor cells off from access to oxygen and the patients' bloodstreams, which limits their ability to produce islets. So ViaCyte's second product -- the one the university is testing -- is a pouch with small pores to increase the production of islets and the distribution of insulin into the blood.

Patients trying this approach do need immunosuppressive drugs, Bellin said, which is why the trial is only for severe cases.

Special oversight

The university requires special oversight of research involving the transplant of embryonic stem cells because of the political sensitivities over the sources of these cells from unused human embryos. However, Bellin said this study did not require that oversight, because the transplant involved islets produced from stem cells -- rather than the actual stem cells.

Romero is hopeful. Married with a 2-year-old daughter, he remains upset over the disease that arrested his life and disabled his father. He ate whatever he wanted out of spite and managed the disease with insulin injections. But as he has aged, and his body has stopped giving clear signals of changes in his blood sugar, he said he needs a better option.

"I spent a lot of years where it would frighten me to a point that I would just neglect my disease," he said. "But my body doesn't have the strength to put up with that anymore."

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