The key to effectively reversing type 1 diabetes might lie in a newly discovered way to transplant pancreatic islets, according to a new research paper published in the medical journal Cell Reports Medicine.
In type 1 diabetes, a person’s immune system erroneously attacks the beta cells, or β cells, in the pancreas. Because these beta cells release the insulin that helps control blood sugar levels, the result of this attack is high blood sugar and, eventually, type 1 diabetes. The beta cells lie in what are called pancreatic islets, which are “islands” that contain different kinds of cells, each of which produces a different hormone that is secreted into the bloodstream. The alpha cells make glucagon, the delta cells make somatostatin, and the beta cells, which comprise 65-80% of the islet cells, make insulin and amylin.
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The idea of treating, or even reversing, type 1 diabetes by transplanting islet cells from a healthy donor has been around for a while, but certain problems have stood in the way. For one, the process is inefficient — the immune system destroys as many as half the transplanted beta cells. Also, these transplants have been done through the liver, which, because it can manage only a limited number of transplants, has led researchers to speculate that another site might work better.
The omentum eyed as a new potential transplant site
According to the authors of the new report, who were led by researchers at Massachusetts General Hospital in Boston, an alternate site worth trying was the omentum, which is, according to the definition given by the National Cancer Institute, “A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen.” The omentum is easier to monitor than the liver because it’s easier to access, and it’s not a vital organ in the way the liver is.
To make the omentum a viable transplant site, the research team combined an enzyme that causes blood clotting with the recipients’ own blood plasma. This procedure enabled the researchers to construct what they called a “bio-degradable matrix” that allowed donor islets to be fixed in the omentum. They then used immunosuppressive therapy to shield the transplanted islets from attack by the immune system. The experiment was performed on what the researchers described as three “nonhuman primates” with type 1 diabetes.
The strategy was successful in restoring both normal blood sugar levels and insulin secretion in the test subjects, and the effects lasted as long as the animals were being evaluated. According to first author Hong Ping Deng, MD, “The achievement of complete glycemic control is attributed to the bioengineering approach that facilitates the process of revascularization and reinnervation for the transplanted islets, which is the first time that such a demonstration has been made in a nonhuman primate model.”
Ji Lei, MD, a principal physician investigator of Transplant Surgery at Massachusetts General and senior corresponding author of the new report, added, “This pre-clinical study can inform the development of new strategies for β cell replacement in diabetes and could change the current paradigm of clinical pancreatic islet transplantation. A clinical trial is being planned to test this approach.”
The researchers also pointed out their bioengineered site in the omentum can host other kinds of genetically engineered cells, especially for liver conditions or metabolic and endocrine problems. Right now, however, the focus is on type 1 diabetes, for which the potential is considerable. According to co-author James F. Markmann, MD, chief of the Division of Transplant Surgery and director of Clinical Operations at the Transplant Center at Massachusetts General, “The application of this strategy, particularly in stem cell-based therapy, has the potential to revolutionize the paradigm for treating patients with type 1 diabetes.”