Antioxidant gel preserves islet function after pancreas removal

Researchers from Northwestern University have developed a new antioxidant biomaterial that could in the future make life much easier for people suffering from chronic pancreatitis.

Key findings of the study

The paper, "Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum," was published June 7 in the journal Science Advances.

Before surgeons remove the pancreas from patients with severe, painful chronic pancreatitis, they first remove clusters of insulin-producing tissue called islets of Langerhans and transplant them into the liver's vascular system. The goal of the transplant is to preserve the patient's ability to control blood glucose levels without insulin injections.

Unfortunately, this process destroys 50-80% of the islets, and a third of patients become diabetic after the operation. Three years after the operation, 70% of patients require insulin injections, which is accompanied by a number of side effects such as weight gain, hypoglycemia and fatigue.

A new approach to transplantation

In the new study, scientists transplanted Langerhans islets into the omentum, a large, flat fatty tissue that lines the intestines, instead of the liver. To create a more favorable microenvironment for the islets, the researchers used an antioxidant and anti-inflammatory biomaterial that quickly turns from a liquid to a gel at body temperature.

Results of animal experiments

In experiments on mice and primates, the gel successfully prevented oxidative stress and inflammatory reactions, significantly improving the survival and functionality of transplanted islets. This is the first time that a synthetic antioxidant gel has been used to preserve the functionality of transplanted islets.

"Although islet transplantation has improved in recent years, long-term results remain unsatisfactory," said Guillermo A. Ameer, who led the study. "Our new synthetic material creates a supportive microenvironment for islet function. In animal testing, it was highly effective and restored normal blood sugar levels."

Advantages of the new biomaterial

"With this new approach, we hope that patients will no longer be forced to choose between the pain of chronic pancreatitis and the complications of diabetes," added Jacqueline Burke, first author of the study.

Role and Prospects

For patients living without a pancreas, side effects such as managing blood sugar levels can be a lifelong challenge. The islets of Langerhans help the body maintain control of blood sugar levels. Without functioning islets, people must frequently monitor their blood sugar levels and inject insulin.

"Living without functional islets puts a huge burden on patients," Burke said. "They have to learn to count carbohydrates, dose insulin at the right time and constantly monitor their glucose levels. It takes a lot of their time and mental energy."

Problems with the current method

But unfortunately, the current standard of care for islets often leads to poor outcomes. After surgery to remove the pancreas, surgeons isolate the islets and transplant them into the liver via portal vein infusion. This procedure has several common complications. Islets in direct contact with the bloodstream undergo an inflammatory response, more than half of the islets die, and transplanted islets can cause dangerous blood clots in the liver. For these reasons, doctors and researchers have been looking for an alternative transplant site.

A new approach using citrate solution

To protect the islets and improve outcomes, Ameer turned to a citrate biomaterial platform developed in his lab with antioxidant properties. In cell cultures, both mouse and human islets stored in citrate gel remained viable for much longer than islets in other solutions. When exposed to glucose, the islets secreted insulin, demonstrating normal functionality.

Integration into tissues

After three months, the body had reabsorbed 80 to 90 percent of the biocompatible gel, by which point it was no longer needed. "What was amazing was that the islets regenerated blood vessels," Ameer said. "The body created a network of new blood vessels to connect the islets to the body. This is an important breakthrough because blood vessels keep the islets alive and healthy."

Ameer plans to test the hydrogel in animal models over a longer period of time next. He also noted that the new hydrogel could be used for a variety of cell replacement therapies, including stem cell therapy for diabetes.