Alginate derivative protects implanted cells from immune system in mouse study
For patients with Type I diabetes, precise control of blood sugar remains difficult to achieve, resulting in a range of long-term medical problems. As an alternative to insulin injections, researchers have been investigating replacement of destroyed pancreatic islet cells with healthy cells. The approach has been used in hundreds of patients but has a major drawback in requiring use of immunosuppressant drugs for the rest of the patients’ lives.
It is hoped that a newly designed material able to encapsulate human islet cells prior to transplantation may further this approach. Tests on mice have demonstrated the efficacy of this approach, with encapsulated human cells demonstrated to ‘cure’ diabetes for up to six months without provoking an immune response.
The basis of this approach is to protect glucose-stimulated insulin-producing cells, derived from stem cells, inside capsules that are engineered to be invisible to the host immune system. Having created a library of almost 800 alginate derivatives, researchers performed several rounds of tests in mice and nonhuman primates. They selected one of the best performers, triazole-thiomorpholine dioxide (TMTD) for further study in diabetic mice. A strain of mice known to have a strong immune system was chosen and human islet cells encapsulated in TMTD were implanted into the intraperitoneal space. Following implantation, the cells immediately began producing insulin in response to blood sugar levels and were able to maintain control over blood sugar levels for the 174-day study.
"The really exciting part of this was being able to show, in an immune-competent mouse, that when encapsulated these cells do survive for a long period of time, at least six months," explained author Omid Veiseh (Koch Institute and Boston Children's hospital, both MA, USA). "The cells can sense glucose and secrete insulin in a controlled manner, alleviating the mice's need for injected insulin."
The researchers’ next step will be to test their new materials in nonhuman primates with a look towards one day performing clinical trials in diabetic patients.
"Being insulin-independent is the goal," summarized first author Arturo Vegas (Boston University, MA, USA). "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."