Making implantable islet cells work for type 1 diabetes

New device would give insulin-producing cells their own oxygen supply so they can live longer after transplant

Jeffrey Bouley
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CAMBRIDGE, Mass.—As with so many ideas in the life sciences, no matter how good and how effective the idea might be, executing it within the human body itself can make even the finest notions impractical. An example would be the idea of transplanting islet cells—the pancreatic cells responsible for producing insulin when blood glucose concentration increases—as a means to treat type 1 diabetes.
It’s an idea that has been around since the 1960s. One of the key problems, though, is that once the islets are transplanted, they will die if they don’t receive an adequate supply of oxygen. In an attempt to finally break down that barrier, researchers at the Massachusetts Institute of Technology (MIT), working with a company called Beta-O2 Technologies, have developed and tested an implantable device that furnishes islet cells with their own supply of oxygen, via a chamber that can be replenished every 24 hours.
“Getting oxygen to these cells is a difficult problem,” said Clark Colton, an MIT professor of chemical engineering and the senior author of the study, which appeared in the April 25 issue of Scientific Reports. “The benefits of this approach are you keep the islets alive to perform their function, you don’t need as much tissue and you reduce the ability of the implants to provoke an immune response.”
According to tests of the device in rat models, almost 90 percent of the islets remained viable for several months, and most of the rats maintained normal blood glucose levels throughout that time.
As MIT notes, there is another benefit of this approach. As it happens, another problem with implanted islet cells is that when the cells die and break down, the resulting fragments of protein and DNA are more likely to attract the attention of the immune system
“By keeping the cells alive, you minimize the immune response,” Colton noted.
Researchers at Beta-O2 Technologies are now working on new versions of the device in which an oxygen storage chamber is implanted below the skin, separate from the islets. This version would only need to be replenished once a week, which could be more appealing for patients.
In some other recent cell-related news at MIT, researchers are exploring some “gut feelings” in terms of intestinal stem cells and aging. As MIT notes, as people age, their intestinal stem cells begin to lose their ability to regenerate. These stem cells are the source for all new intestinal cells, so this decline can make it more difficult to recover from gastrointestinal infections or other conditions that affect the intestine. According to biology researchers at the university, though, this age-related loss of stem cell function can be reversed by a 24-hour fast—at least in mice.
Reportedly, fasting dramatically improves stem cells’ ability to regenerate, in both aged and young mice. In fasting mice, cells begin breaking down fatty acids instead of glucose, a change that stimulates the stem cells to become more regenerative. The researchers found that they could also boost regeneration with a molecule that activates the same metabolic switch. Such an intervention could potentially help older people recovering from gastrointestinal infections or cancer patients undergoing chemotherapy, the researchers say.
“Fasting has many effects in the intestine, which include boosting regeneration as well as potential uses in any type of ailment that impinges on the intestine, such as infections or cancers,” said Omer Yilmaz, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and one of the senior authors of the study. “Understanding how fasting improves overall health, including the role of adult stem cells in intestinal regeneration, in repair and in aging, is a fundamental interest of my laboratory.”
David Sabatini, an MIT professor of biology and member of the Whitehead Institute for Biomedical Research, is also a senior author of the paper, which appeared in the May 3 issue of Cell Stem Cell.
“This study provided evidence that fasting induces a metabolic switch in the intestinal stem cells, from utilizing carbohydrates to burning fat,” Sabatini commented. “Interestingly, switching these cells to fatty acid oxidation enhanced their function significantly. Pharmacological targeting of this pathway may provide a therapeutic opportunity to improve tissue homeostasis in age-associated pathologies.”
And, since we moved from islet cells to stem cells (and aging), let’s make a transition from stem cells and aging to aging and muscles—and stick to the MIT campus once again.
In news from much earlier in the spring, researchers made some key findings in an effort aimed at restoring muscle mass. The dilemma tackled by researchers in this case was that as we get older, our endurance declines, in part because our blood vessels lose some of their capacity to deliver oxygen and nutrients to muscle tissue.
An MIT-led research team discovered that it can reverse this age-related endurance loss in mice by treating them with a compound that reactivates longevity-linked proteins called sirtuins, promoting the growth of blood vessels and muscle—and boosting the endurance of elderly mice by up to 80 percent.
If the findings translate to humans, this restoration of muscle mass could help to combat some of the effects of age-related frailty, which often lead to osteoporosis and other debilitating conditions.
“We’ll have to see if this plays out in people, but you may actually be able to rescue muscle mass in an aging population by this kind of intervention,” remarked Leonard Guarente, the Novartis Professor of Biology at MIT and one of the senior authors of the study. “There’s a lot of crosstalk between muscle and bone, so losing muscle mass ultimately can lead to loss of bone, osteoporosis and frailty, which is a major problem in aging.”

Jeffrey Bouley

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