Encapsulated cells could free diabetics from insulin injections

The researchers used a material called alginate, seen here in an electron microscopy image, to shield insulin-producing cells from the body's immune system(Credit: MIT)

Type 1 diabetes patients have to constantly monitor their blood sugar levels, regularly injecting insulin to make sure they stay healthy. Not only is this a burden for patients, but it can also be difficult to get right, often resulting in long-term medical problems. A team of researchers, including scientists from MIT, has been working on a better system. They're developing a transplantable capsule that can carry cells able to replace the patient's lost ability to produce insulin, and that isn't rejected or rendered useless by the host's body.

The idea of implanting pancreatic islet cells that are able to monitor glucose and provide insulin release isn't actually new. In fact, hundreds of patients have undergone such treatment, but every attempt has suffered from the same issue. If left unchecked, the subject's immune system eventually attacks the transplanted cells, making it necessary patients to take immunosuppressant drugs for the rest of their lives.

A team of scientists lead by researchers from MIT and Boston Children's Hospital has worked to adjust the treatment in order to remove that drawback. They started by working with a material called alginate, which is isolated from brown algae. The material is able to encapsulate cells without causing them harm, while allowing sugars, proteins and other molecules to pass through it.

Those properties made the alginate a good candidate for the implantable capsule. However, previous work had shown that when the material is implanted in primates and humans, scar tissue builds up around it, eventually making the device useless.

In order to ensure that the material would work for long-term use, the researchers began to add different small molecules to the polymer chain. All in all, they tried almost 800 derivatives, eventually identifying triazole-thiomorpholine dioxide (TMTD) as the best choice for further study.

They inserted pancreatic islet cells into the TMTD alginate and tested its effects in a strain of laboratory mice with particularly strong immune systems. The islet cells were generated from human stem cells, and the alginate capsules containing them were placed in a region of the rodents' abdominal cavity known as the intraperitoneal space.

Once implanted, the islet cells responded to the blood sugar levels immediately, and started to produce insulin. Throughout the entire course of the study – a full 174 days – the implanted device worked perfectly, keeping blood sugar levels within safe boundaries.

The modified alginate was also tested in primates, though without islet cells being inserted. Those tests, which featured 1.5 mm (0.06 in)-diameter capsules, showed that the material can remain the system for long periods of time (at least six months) without scar tissue building up around it.

With those positive results in mind, the researchers plan to continue to test the device, working first with nonhuman primates, before eventually moving on to human trials. Even assuming that future tests support these early findings, it will be some time before the new treatment might become available to patients. Nevertheless, the work represents a big step on the road towards a much easier method for long-term blood sugar control.

"Being insulin-independent is the goal," said paper author Arturo Vegas. "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."

The findings were published in the journal Nature Medicine.

Source: MIT

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