JDRF-funded researchers team up to speed progress
Collaboration among experts with different specialties can galvanize research progress by uniting the brightest minds in pursuit of a common goal. So JDRF was thrilled when three of our funded scientists joined forces to develop a potential encapsulated islet cell therapy for the treatment of type 1 diabetes (T1D): chemical engineer Daniel Anderson, Ph.D., and biomaterial engineer Robert Langer, Sc.D.—both researchers at the Massachusetts Institute of Technology and Boston Children’s Hospital—and cell biologist Douglas Melton, Ph.D.—a researcher at Harvard University.
In research newly published in Nature Biotechnology and Nature Medicine, the all-star team showed it was successful in combining Drs. Anderson and Langer’s novel encapsulation material with Dr. Melton’s islet cells—developed from human embryonic stem cells (hESCs)—to create a prototype therapy capable of normalizing blood glucose in a mouse model of T1D for up to six months. If the therapy performs this well in large animal studies, the researchers hope to carry out clinical trials and eventually translate it into a therapeutic strategy for blood-glucose management in people with T1D.
“With the long-term aim of establishing insulin independence without the need for immune suppression, encapsulated cell therapies have the potential to eliminate the daily burden of managing the disease for months, possibly years, at a time,” said JDRF Vice President of Discovery Research Julia Greenstein, Ph.D. “JDRF is excited by these findings and we hope to see this research progress into human clinical trials and ultimately a potential new T1D therapy,” she added.
In the approach under development by Drs. Anderson, Langer and Melton, islet cells produced from hESCs are encased in specially modified alginate capsules that shield them from immune attack when placed in the body. Dr. Melton’s method for deriving pancreatic islets from hESCs created a plentiful supply of islet cells for therapeutic use. But the cells are vulnerable to immune attack within the body. Alginate can protect the cells from immune attack without hindering their function, but it prompts a biological reaction that eventually renders the capsules ineffective. Drs. Anderson and Langer have been carefully adapting the alginate material to improve its tissue compatibility.
As reported in Nature Biotechnology, the researchers created and tested nearly 800 alginate derivatives and found that one modification called triazole-thiomorpholine dioxide (TMTD) was the most biocompatible in both mice and large animals. Working with Dr. Melton, they used TMTD to encapsulate islet cells and then implanted the capsules in mice. The results published in Nature Medicine show the implanted cells immediately began producing insulin and maintained healthy blood-glucose levels until they were removed six months later.
This research represents progress toward designing successful encapsulated islet cell therapies on two fronts: creating encapsulation materials that are biocompatible, and showing that islet cells developed using Dr. Melton’s technique can function as a component of such a therapy. In the future, the researchers may focus on optimizing alginate’s biocompatibility with the human body in order to move this potential therapy into clinical testing phase.
The studies were funded by JDRF in collaboration with The Leona M. and Harry B. Helmsley Charitable Trust.
Why It Matters
A multidisciplinary approach can provide the focus, perspective and insight that make research objectives attainable. By facilitating collaborations among experts in different fields, JDRF is pushing the pace of science to develop promising therapies more quickly.