photo credit: This beta cell’s “stealth shield,” as seen under electron microscopy, prevents its destruction by the erring, aggressive immune system of the mouse. Vegas et al./Nature
For those with type 1 diabetes, regularly injecting themselves with insulin is part and parcel of their daily lives. This form of treatment hasn’t advanced much for nearly a century, so it will come as good news that researchers at the Massachusetts Institute of Technology (MIT) are on the verge of a breakthrough. As a study in Nature Medicine reveals, insulin-producing beta cells made from human stem cells have been shown to effectively “switch off” diabetes in mice for up to six months.
Within a healthy person’s pancreas, clusters of beta cells produce insulin in order to counteract rising blood sugar levels. Someone suffering from type 1 diabetes is unable to control their blood sugar levels, as their own immune system attacks and destroys these insulin-producing cells. Type 1 diabetes, which makes up roughly 10 percent of all diabetes cases, is therefore a type of autoimmune disease, and is currently incurable.
In 2014, a team led by Harvard University made a significant step in developing a bonafide cure. Using human embryonic stem cells, the team induced them into becoming beta cells in large quantities – up to hundreds of millions at a time, enough to transplant them into ahyperglycemic mouse and watch them dramatically reduce the animal’s blood sugar levels.
Unfortunately, as with the mouse’s original beta cells, its faulty immune system destroyed the new, transplanted beta cells fairly quickly, so the technique didn’t provide lasting benefits. Now, a team at MIT has found a way to hide these beta cells from the self-destructive immune system of mice suffering from type 1 diabetes.
From previous research, it was known that it is possible to encase various transplanted beta cells in alginate gel, a material derived from brown algae. This initially shields the presence of the beta cells from the erring immune system within primates, including humans, but relatively quickly scar tissue begins to form around these alginate capsules, indicating the immune system has begun to destroy them.
A stem cell-originated beta cell, encapsulated within an alginate capsule shielding it from the malfunctioning immune system of the host – the perfect Trojan horse for type 1 diabetes sufferers. Vegas et al./Nature
The MIT researchers decided to modify the chemical structure of the alginate capsules in as many different ways as possible to try and build a better shield for the beta cells. “We made all these derivatives of alginate by attaching different small molecules to the [large molecule] chain,” said Arturo Vegas, lead author of the study and an accompanying paper in Nature Biotechnology, in a statement. They hoped that one of the 800 alginate derivatives would have “the ability to prevent recognition by the immune system.”
Luckily, one variant did indeed prove to be effective, in both mice and nonhuman primates. Known as triazole-thiomorpholine dioxide (TMTD), this variant was shown to be able to hide from white blood cells within hyperglycemic mice with a very strong immune system. Following the transplant, these beta cells began to immediately produce insulin, and brought the blood sugar levels down to healthy levels for a remarkable 174 days, a significant length of time considering their lifespan.
The next stage, of course, is human trials, after several more nonhuman primate trials confirm this technique’s efficacy. The ultimate aim would be to transplant these cells into people suffering from type 1 diabetes, allowing them to produce their own insulin. This would essentially cure the disease, and would render regular insulin injections a thing of the past.