In sort 1 diabetes, an autoimmune response assaults the pancreas’s insulin-producing beta cells, resulting in marked fluctuations in blood sugar ranges. Lifelong each day insulin therapies are customary for sufferers, however changing misplaced beta cells by way of transplants of islets, a bunch of cells within the pancreas, represents a sexy choice. This technique requires that sufferers take lifelong immunosuppressive medication to forestall rejection, nevertheless. To deal with this shortcoming, a workforce at Massachusetts General Hospital (MGH) and Harvard Medical School collaborated with researchers on the Georgia Institute of Technology and the University of Missouri to develop a novel biomaterial that, when combined with islets, permits islets to outlive after transplant with out the necessity for long-term immunosuppression.
In a preclinical research carried out at MGH and printed in Science Advances, the researchers examined the biomaterial — which features a novel protein referred to as SA-FasL that promotes immune tolerance and is tethered to the floor of microgel beads — in a nonhuman primate mannequin of sort 1 diabetes. The materials was combined with islets after which transplanted to a bioengineered pouch fashioned by the omentum — a fold of fatty tissue that hangs from the abdomen and covers the intestines. After transplantation, animals acquired 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,” says lead creator Ji Lei, MD, MBA, an affiliate immunologist at MGH and an assistant professor 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 additionally director of the Human Islet/Cell Processing Special Service cGMP Facility at MGH, notes that transplanting islets to the omentum has a number of benefits over the present medical 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 explains. “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-corresponding creator James F. Markmann, MD, PhD, chief of the Division of Transplant Surgery and director of Clinical Operations on the Transplant Center at MGH stresses that the non-human primate research is a extremely related pre-clinical animal mannequin. “This localized immunomodulatory strategy succeeded without long-term immunosuppression and shows great potential for application to type 1 diabetes patients,” he says.
A medical trial is being planned based on the researchers’ results.
Additional research authors embrace 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.