In type 1 diabetes, an autoimmune action attacks the pancreas’s insulin-producing beta cells, resulting in significant changes in blood glucose levels. Lifelong everyday insulin treatments are basic for clients, however changing lost beta cells through transplants of islets, a group of cells in the pancreas, represents an appealing alternative. This technique needs that clients take long-lasting immunosuppressive drugs to avoid rejection, nevertheless. To address this drawback, a group at Massachusetts General Hospital (MGH) and Harvard Medical School worked together with scientists at the Georgia Institute of Technology and the University of Missouri to establish an unique biomaterial that, when combined with islets, permits islets to make it through after transplant without the requirement for long-lasting immunosuppression.
In a preclinical research study performed at MGH and released in Science Advances, the scientists checked the biomaterial — that includes an unique protein called SA-FasL that promotes immune tolerance and is connected to the surface area of microgel beads — in a nonhuman primate design of type 1 diabetes. The product was combined with islets and after that transplanted to a bioengineered pouch formed by the omentum — a fold of fat that hangs from the stomach and covers the intestinal tracts. After hair transplant, animals got a single anti-rejection drug (rapamycin) for 3 months.
“Our strategy to create a local immune-privileged environment allowed islets to survive without long-term immunosuppression and achieved robust blood glucose control in all diabetic nonhuman primates during a six-month study period,” states lead author Ji Lei, MD, MBA, an associate immunologist at MGH and an assistant teacher of Surgery at Harvard Medical School. “We believe that our approach allows the transplants to survive and control diabetes for much longer than six months without anti-rejection drugs because surgical removal of the transplanted tissue at the end of the study resulted in all animals promptly returning to a diabetic state.”
Lei, who is likewise director of the Human Islet/Cell Processing Special Service cGMP Facility at MGH, keeps in mind that transplanting islets to the omentum has numerous benefits over the existing clinical method of transplanting to the liver. “Unlike the liver, the omentum is a non-vital organ allowing its removal should undesired complications be encountered,” he describes. “Thus, the omentum is a safer location for transplants to treat diabetes and may be particularly well suited for stem-cell-derived beta cells and bio-engineered cells.”
Co-matching author James F. Markmann, MD, PhD, chief of the Division of Transplant Surgery and director of Clinical Operations at the Transplant Center at MGH worries that the non-human primate research study is an extremely appropriate pre-clinical animal design. “This localized immunomodulatory strategy succeeded without long-term immunosuppression and shows great potential for application to type 1 diabetes patients,” he states.
A clinical trial is being planned based on the scientists’ results.
Additional research study authors consist of María M. Coronel, Esma S. Yolcu, Hongping Deng, Orlando Grimany-Nuno, Michael D. Hunckler, Vahap Ulker, Zhihong Yang, Kang M. Lee, Alexander Zhang, Hao Luo, Cole W. Peters, Zhongliang Zou, Tao Chen, Zhenjuan Wang, Colleen S. McCoy, Ivy A. Rosales, Haval Shirwan and Andrés J. García.
This work was supported by the Juvenile Diabetes Research Foundation, the National Institutes of Health, and the National Science Foundation.
Materials supplied by Massachusetts General Hospital. Note: Content might be modified for design and length.