Current treatment approaches for type I diabetes, such as pancreatic islet transplantation, are quite promising. However, they are inefficient and can result in the loss of half of the transplanted beta cells during immune attack. Furthermore, the liver can only take in a limited volume of transplanted tissue. This led researchers to identify an alternative site with a hospitable environment - the omentum, which is a fatty tissue that starts in the stomach and spreads all over the intestine.
A research team from Massachusetts General Hospital developed an effective procedure to transplant pancreatic islets which can reverse type I diabetes in nonhuman primates. In optimizing the omentum, they used topical recombinant thrombin and the recipient’s own plasma in engineering a biodegradable matrix by which donor islets are immobilized onto the omentum.
What makes omentum better than the liver is that it is easily accessible for monitoring processes and its non-vital site status allows the removal of transplanted tissue if complications occur, either from the stem cell-derived islets or islets from the donors. Additionally, the omental site can accommodate other types of genetically engineered cells, particularly for liver-based or inherited metabolic or endocrine disorders.
Alongside an immunosuppressive therapy, this strategy managed to normalize blood glucose levels and restored glucose-responsive insulin secretion on three of nonhuman primates with type I diabetes. Hong Ping Deng, MD, MSc, first author, said that the complete glycemic control can be ascribed to the bioengineering approach that aids the process of revascularization and reinnervation for the transplanted islets.
This preclinical study informs the development of novel techniques and challenges the current paradigm in pancreatic islet transplantation. Moreover, the investigators are also examining the broad applications of transplanting stem cell-derived islets, which successfully cured a case of type I diabetes for the first time in human history back in 2022. Though concerns, such as the possibility of tumor development surfaced.
James F. Markmann, MD, PhD, one of the co-authors, stressed that the non-human primate studies are highly translational preclinical animal model and the application of this strategy could revolutionize the approach in treating patients with type I diabetes.