New research shows that by encapsulating them in a new biomaterial, implanted human pancreatic cells can withstand attack by the immune system in mice for up to 6 months, while maintaining their ability to sense low blood sugar and produce insulin in response.
The achievement – which brings closer the day when type 1 diabetes patients will no longer need daily insulin injections – is marked by the publication of two papers: one in Nature Medicinethat covers the tests in mice and the other in Nature Biotechnology that covers the development of the biomaterial.
The findings are part of ongoing studies to develop encapsulated islet cell therapy for treatment of type 1 diabetes.
Type 1 diabetes arises when the immune system attacks the islet cells in the pancreas, destroying their ability to make insulin, the hormone that the body uses to control glucose or blood sugar.
Patients with type 1 diabetes have to measure their glucose level several times a day and inject themselves with insulin to stop it getting too high.
Apart from the inconvenience and restriction to daily life imposed by regular insulin injections, precise control of glucose in the blood is difficult to achieve, and it carries a raised risk of long-term medical problems.
Researchers are working on ways to improve treatments for type 1 diabetes. One of these is to replace the destroyed islet cells in the pancreas with healthy cells that can restore glucose monitoring and insulin release.
However, while this has already been tried in hundreds of patients, success is limited by the fact that they have to be on immunosuppressant drugs for life because their immune system still sees the implanted cells as enemies and attacks them.
Challenge finding biomaterial that evades immune system
In the new papers, researchers – from the Massachusetts Institute of Technology and Harvard University in Cambridge, MA, as well as from Boston Children’s Hospital and other centers – suggest that encapsulating the islet cells in a new biomaterial that they developed could overcome the immune attack problem.
The new biomaterial is a derivative of alginate, a material originally isolated from brown algae.
Researchers have found it is possible to use alginate gels to encapsulate cells without harming them. It is also possible to make the gels allow molecules such as sugar and proteins to move through them, so the encapsulated cells can detect and respond to biological changes.
However, in tests where they implanted gel capsules in primates and humans, researchers found that the capsule surfaces eventually get covered in scar tissue, impeding the passage of molecules and the effectiveness of any encapsulated devices.
In the Nature Biotechnology paper, the team describes how they experimented with lots of different versions of alginate, as first author Arturo Vegas, formerly with MIT and Boston Children’s Hospital and now an assistant professor at Boston University, explains:
“We made all these derivatives of alginate by attaching different small molecules to the polymer chain, in hopes that these small molecule modifications would somehow give it the ability to prevent recognition by the immune system.”
Encapsulating islet cells kept them working for 6 months
After sifting through hundreds of alginate derivatives, the researchers settled on triazole-thiomorpholine dioxide (TMTD) and tested it in diabetic mice with a strong immune system. They implanted human islet cells encapsulated in TMTD into the animals’ abdominal cavity.
The implanted cells immediately began producing insulin in response to blood glucose levels and continued to do so for 174 days, the whole period of the study.
The researchers also tested the new biomaterial – in the form of empty capsules – by implanting it into the abdominal cavities of non-human primates. The capsules lasted at least 6 months without accumulating scar tissue.
When they investigated why the new biomaterial works so well, the team discovered that the presence of the triazole ring – comprising two carbon atoms and three nitrogen atoms – may interfere with the immune system’s ability to recognize the material as foreign.
Sarah Johnson, UK director of policy and communication at JDRF, a type 1 diabetes charity that part-funded the research, says:
“It’s significant to see a study of this length return such promising results. If this study can be replicated in humans then one day we could potentially free people with type 1 diabetes from a life of insulin injections.”
Reports of this work follows the publication of another study Medical News Today learned about recently where researchers created insulin-producing pancreatic cells from human skin cells. The study also presents significant advancements in cellular reprogramming that should lead to the ability to manufacture trillions of the target cells in a controlled manner.
Written by Catharine Paddock PhD