Treatment With Pancreatic Cells Could Improve Diabetes Therapy

Article

Encapsulated human islet cells could improve maintenance of blood sugar levels in patients with diabetes.

A new treatment that encapsulates pancreatic cells has the potential to help patients with type 1 diabetes, according to a recent study.

Patients with diabetes have to monitor their blood sugar multiple times a day and inject themselves with insulin to maintain healthy levels. However, getting control of blood sugar levels can be difficult and result in large fluctuations that can cause an array of long-term medical problems for patients.

Prior research suggested that replacing destroyed pancreatic islet cells with healthy cells could take over glucose monitoring and insulin release.

Although this has been used on hundreds of patients, researchers found that immune systems would attack the transplanted cells, resulting in patients having to take immunosuppressant drugs for the rest of their lives.

Many years ago, researchers looked to create a way to turn encapsulated islet cell transportation into a possible therapeutic approach. They looked at alginate gels, which are materials isolated from brown algae, and can be used to encapsulate cells without causing them any harm.

Alginate gels also allow sugar and proteins to move through, allowing cells inside to sense and respond to biological signals.

Unfortunately, when alginate capsules were implanted in humans and primates, scar tissue would build up around the capsules, making it ineffective.

Therefore, researchers set out to find a different way to use alginate without provoking that response.

"We decided to take an approach where you cast a very wide net and see what you can catch," said study author Arturo Vegas. "We made all these derivatives of alginate by attaching different small molecules to the polymer chain, in hopes that these small molecule modifications would somehow give it the ability to prevent recognition by the immune system."

The design used a material that encapsulated human islet cells before transplanting them. The results of the study showed that these cells could cure diabetes for up to 6 months without an immune response.

Researchers created a library of almost 800 alginate derivatives and did tests on mice and nonhuman primates. Triazole-thiomorpholine dioxide (TMTD) seemed to be the most promising, so they performed tests on diabetic mice by choosing a strain of mice that had a strong immune system.

They implanted human pancreatic islet cells generated from human stem cells which were encapsulated in TMTD into the intraperitoneal space.

Immediately after the implantation, the cells began producing insulin in response to the blood sugar levels. For the length of the 174 day study, the treatment was able to keep sugar levels under control.

"The really exciting part of this was being able to show, in an immune-competent mouse, that when encapsulated these cells do survive for a long period of time, at least 6 months," said study author Omid Veiseh. "The cells can sense glucose and secrete insulin in a controlled manner, alleviating the mice's need for injected insulin."

Now, researchers are looking to perform further tests on their new materials in nonhuman primates with a goal to hold clinical trials for diabetic patients.

"Being insulin-independent is the goal," Vegas added. "This would be a state-of-the-art way of doing that, better than any other technology could. Cells are able to detect glucose and release insulin far better than any piece of technology we've been able to develop."

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