For the 1.25 million Americans with type 1 diabetes—in which the immune system attacks the pancreas, and makes it difficult for patients to control blood sugar—daily injections of insulin are a way of life. Now, two breakthrough studies done by researchers from MIT in collaboration with Boston’s Children’s Hospital have found a way to encapsulate healthy pancreatic or “islet” cells and transplant them into diabetic mice without an immune response, essentially curing the mice for the duration of the study. (The studies were published in Nature Biotechnology and Nature Medicine, respectively.) These finds hold great promise for a human cure.
Researchers have been studying ways to replace the damaged islet cells in diabetes for years, and moreover, to figure out a way to protect them so the immune system can’t destroy them. Omid Veiseh, a lead author on both studies and a postdoctoral fellow at MIT, tells mental_floss, “We asked the question, 'What if we could protect these cells in a capsule that is porous, so sugars and proteins can pass through, but immune cells would be unable to interact with the stem cells and kill them off?'”
Part of the challenge of finding the right encapsulating material, says Veiseh, is that “the body recognizes these materials as foreign and starts walling them off and building scar tissue, which is a barrier to nutrients and oxygen, so the cells inside those capsules didn’t survive that long.”
That is, until now: “We’ve developed a new kind of material, a polysaccharide, alginate derived from seaweed, that we make the capsules from," Veiseh says. "It’s exciting because we’ve shown we can put them into even nonhuman primates and the immune cells can still survive and thrive.”
Getting to this version of the alginate capsule required extensive testing. Researchers created a library of nearly 800 alginate derivatives before testing these in mice and nonhuman primates. They ultimately settled on one called triazole-thiomorpholine dioxide (TMTD). “It’s able to function very well, resisting fibrosis in primate models, and so we put them into diabetic mice,” Veisah describes.
The human pancreatic stem cells used in the study were generated using a technique pioneered by Harvard University's Douglas Melton, who is also a co-author on the Nature Medicine study. Then, through a small laparoscopic surgery, they transplanted the encapsulated cells, which are about the size of small caviar fish eggs, into the abdominal cavities of the mice.
“Being able to cure a diabetic animal for up to six months—and we think we could have gone further if the study was longer—was really impressive, and not something we have been able to achieve before,” Veiseh says. “That it was done with stem cells makes it more viable for clinical translation, because you have a replenishable source.”
In fact, since Melton’s study showed that a patient’s skin cell could be converted to a stem cell, one day islet cells could theoretically be derived from a patient’s own cells.
The team will next study the effect of the encapsulated islet cells on nonhuman primates, and, with funding from JDRF Diabetes Foundation, says Veiseh, “we are looking to ways to get this in the clinic faster.”