research

Diabetes researchers look at cellular-level transplants as bridge to a cure

 

Researchers at UM’s Diabetes Research Institute say the transplants of insulin-producing cells could move soon from study to regular practice.

lisensee@MiamiHerald.com

Dr. Camilo Ricordi is not resting on his laurels. He marked a milestone in 1986 when he created the Ricordi Chamber, which successfully isolates the pancreas’ special cells that produce insulin. The device is still used worldwide.

Instead, Ricordi is pursuing other research that could bridge the path to a real, lifetime cure to diabetes. No gadgets, no insulin injections, no further health complications.

As the director of the Diabetes Research Institute at the University of Miami, Ricordi and some 140 other doctors, scientists and professionals take a collaborative approach to a singular goal to cure diabetes. The chronic disease affects 24 million people in the United States and is a leading cause of blindness, kidney failure, cardiovascular issues and amputations of lower limbs. As many as one in three U.S. adults could have diabetes by 2050, if current trends continue, according to the Centers for Disease Control and Prevention.

Ricordi has had success with the latest research that transplants those clusters of special cells, called islets, in patients with severe Type 1 diabetes. Type 1 diabetes is an autoimmune disease while Type 2 diabetes is associated with obesity, poor diet, an inactive lifestyle and more hereditary factors. Instead of transplanting a whole organ, researchers insert the islets in the pancreas.

Patients with the transplants have not suffered worsening retina problems and with new strategies like anti-inflammatory drugs, 50 percent stay off insulin for five years, a rate comparable to those who have had a pancreas transplant, Ricordi said.

Ricordi said one clinical trial is poised to pursue approval from the U.S. Food and Drug Administration next year for islet transplantations to move beyond research and into more regular practice.

“He is one of the world leaders in islet transplantation,” said Dr. Thomas Eggerman, director of the clinical islet transplantation program at the National Institutes of Health’s division of diabetes, endocrinology and metabolic diseases. Eggerman has collaborated with Ricordi on projects, including an international consortium in islet transplantation.

But there are still hurdles to the ultimate goal.

One challenge is that few people can benefit from the islet transplantations. Still considered research, the transplants are hampered by other issues. Donor cells are scarce and those with transplants need long-term anti-rejection drugs so their immune systems don’t attack the foreign cells.

“The hope is that with this experience, we can find another treatment -- we can gain the experience to apply to other cells that produce insulin,” Eggerman said.

Ricordi and other researchers are excited about other parallel research:

• A new trial in conducting transplants that could eliminate the need of anti-rejection drugs by using the donor’s bone marrow cells to replace the recipient’s immune system.

• New materials to encapsulate and protect the islet transplants from the body’s immune system.

• New ways to deliver the anti-rejection drugs just to the cells that need it, instead of the entire body.

• Using cells from alternative sources, like targeting progenitor cells from a patient’s own pancreas, to regenerate as those special insulin-producing cells. That would eliminate the need for transplants and anti-rejection drugs.

Those anti-rejection drugs are a problem. They take a toll on the transplanted cells and the entire body, making it more susceptible to other diseases.

“We have to take the next step, now that we’ve proved that we can transplant these cells. How can we make them survive longer? How can we not use the anti-rejection drugs?” said Dr. Cherie Stabler, associate professor of biomedical engineering and surgery at the University of Miami Miller School of Medicine and director of the tissue engineering laboratory at the Diabetes Research Institute.

She and Ricordi are very excited about creating capsules for the transplanted cells to protect them from the body’s immune system. On the surface of cells, there are antigens, which Stabler compared to flags. Every patient would have a different pattern. “When you have a pattern that’s different, the immune system recognizes that’s not my flag, so it attacks it,” she said. “We take the islet and we encapsulate it in a material to hide that flag.”

Currently researchers are experimenting with two primary materials: alginate found in seaweed and jello-like material already used to encapsulate drugs to improve delivery.

One problem, Stabler said, is shrinking the capsule to the right size. Current encapsulations is used at the micro-level; for cells, it’s needed at smaller level, currently it’s like putting a person inside a football field. That deprives the cells of nutrients like oxygen. “We have very promising results in preclinical models, we’re very excited about that,” Stabler said.

In addition, Ricordi is poised to start work with other researchers, including Dr. Suzanne Ildstad at the University of Louisville, to complete transplants without the use of anti-rejection drugs. The idea is to introduce the immune system of the donor, with the bone marrow cells, to the recipient. “This could be ... I don’t want to say the ‘c’ word. But if it works, in two years we could say ‘ta-da’ ” Ricordi said.

Ultimately, they want to help people like Kelvin Bacon, 45, who has lived with Type 1 diabetes for 29 years. Bacon is a patient at Jefferson Reaves Sr. Health Center in Overtown, one of Jackson Health System’s primary care clinics, where Bacon has learned tools, like diet tips, to manage the disease. He still needs insulin injections every day and checks his blood sugar levels three or four times a day. He had heard about th possibility of transplants.

“I wish they would move forward with that,” Bacon said. “I know it would be beneficial, there are a lot of diabetics.”

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