Novel biomaterial prevents rejection of transplants for type 1 diabetes

BOSTON — In type 1 diabetes, an autoimmune response attacks the insulin-producing beta cells of the pancreas, leading to marked fluctuations in blood sugar. Lifelong daily insulin treatments are the norm for patients, but replacing lost beta cells with transplants of islets, a group of cells from the pancreas, is an attractive option. This strategy, however, requires patients to take immunosuppressive drugs for life to prevent rejection. To address this shortcoming, a team from Massachusetts General Hospital (MGH) and Harvard Medical School collaborated with researchers from the Georgia Institute of Technology and the University of Missouri to develop a new biomaterial that, when mixed to islets, allows the islets to survive after transplantation. without the need for long-term immunosuppression.

In a preclinical study conducted at MGH and published in Science Advances, researchers tested the biomaterial – which includes a novel protein called SA-FasL that promotes immune tolerance and is attached to the surface of microgel beads – in a primate model. non-human type 1 diabetes. The material was mixed with islets and then transplanted into a bioengineered pouch formed by the omentum, a fold of fatty tissue that hangs down from the stomach and covers the intestines. After transplantation, the animals received a single anti-rejection drug (rapamycin) for three months.

“Our strategy to create a local immune-privileged environment enabled islets to survive without long-term immunosuppression and achieved robust glycemic control in all diabetic non-human primates over a study period. six months,” says lead author Ji Lei, MD, MBA, MGH associate immunologist and assistant professor of surgery at Harvard Medical School. “We believe that our approach enables the grafts to survive and control diabetes for well over six months without anti-rejection drugs, as surgical removal of the grafted tissue at the end of the study resulted in the rapid return of all animals to a diabetic state.”

Lei, who is also director of the cGMP facility of the special human islet/cell processing department at MGH, notes that islet transplantation into the omentum has several advantages over the current clinical approach to transplantation in liver. “Unlike the liver, the omentum is a non-vital organ that can be removed in the event of unwanted complications,” he explains. “Thus, the omentum is a safer place for diabetes treatment transplants and may be particularly well suited for stem cell-derived beta cells and bio-engineered cells.”

Co-corresponding author James F. Markmann, MD, PhD, Chief of the Division of Transplant Surgery and Director of Clinical Operations at the MGH Transplant Center points out that the non-human primate study is a very important preclinical animal model. relevant. “This localized immunomodulatory strategy was successful without long-term immunosuppression and shows great potential for application to type 1 diabetic patients,” he says.

A clinical trial is planned based on the researchers’ findings.

Other study authors include 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.

About Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is Harvard Medical School’s first and largest teaching hospital. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and includes more than 9,500 researchers working in more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in U.S. News & World Report’s list of “America’s Best Hospitals.” MGH is a founding member of the Mass General Brigham Health Care System.

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