In type 1 diabetes, the autoimmune response attacks the pancreatic beta cells that produce insulin, leading to marked fluctuations in blood sugar levels. Lifelong daily insulin treatment is standard for patients, but replacing lost beta cells through islet transplantation, a group of cells in the pancreas, is an attractive option. However, this strategy requires patients to take lifelong immunosuppressive drugs to prevent rejection. To address this shortcoming, the Massachusetts General Hospital (MGH) team and Harvard Medical School teamed up with scientists from the Georgia Institute of Technology and the University of Missouri to develop a new biomaterial that, mixed with islets, allows islets to survive post-transplantation. without the need for prolonged immunosuppression.
In a preclinical study conducted at MGH and published in Advances in science, researchers tested a biomaterial – which includes a new protein called SA-FasL, which promotes immune tolerance and is bound to the surface of microgel beads – in a model of non-human type 1 diabetes. The material was mixed with islets and then transplanted into a bioengineering bag formed by an omentum – a fold of adipose tissue that hangs from the stomach and covers the intestines. After transplantation, the animals received one anti-rejection drug (rapamycin) for three months.
“Our strategy to create a local immune environment has allowed the islands to survive without long-term immunosuppression and has achieved robust blood glucose control in all primate diabetics over a six-month study period,” said lead author Gee Lei, MD, MD. -MGH immunologist and associate professor of surgery at Harvard Medical School. “We believe that our approach allows transplants to survive and control diabetes for much longer than six months without anti-rejection drugs, because surgical removal of transplanted tissue at the end of the study resulted in all animals rapidly returning to diabetic status.”
Lei, who is also the director of the cGMP’s special service for the treatment of human islets / cells at MGH, notes that transplantation of islets to the omentum has several advantages over the current clinical approach to liver transplantation. “Unlike the liver, the omentum is a non-living organ that allows it to be removed in the event of unwanted complications,” he explains. “Thus, the omentum is a safer place to transplant for the treatment of diabetes and may be particularly suitable for beta cells derived from stem cells and biologically engineered cells.”
Co-correspondent James F. Markman, MD, PhD, Head of Transplant Surgery and Director of Clinical Operations at the Transplant Center at MGH emphasizes that primate research is a very relevant preclinical model in animals. “This localized immunomodulatory strategy has succeeded without prolonged immunosuppression and shows great potential for use in patients with type 1 diabetes,” he says.
According to the researchers, a clinical study is planned.
Additional study authors include Maria M. Coranel, Esma S. Yolku, Hongping Deng, Orlando Grimani-Nuna, Michael D. Hankler, Wahap Ulker, Jihong Yang, Kang M. Lee, Alexander Zhang, Hao Luo, Cole W. Peters, Zhongliang Zou, Tao Chen, Zhenjuang Wang, Colin S. McCoy, Ivy A. Rosales, Haval Shirvan and Andres J. Garcia.
This work was supported by the Juvenile Diabetes Research Foundation, the National Institutes of Health and the National Science Foundation.
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