INSIDE OUR LABS: MECHANISMS OF ISLET TRANSPLANT IMMUNE TOLERENCE
Midhat Abdulreda, Ph.D. is an Associate Professor of Surgery at the Diabetes Research Institute (DRI). Since becoming a part of the DRI in 2007, Dr. Abdulreda’s research seeks to better understand the complex immunology of type 1 diabetes (T1D) to improve islet transplantation methodologies and glycemic control post-transplantation. He innovatively studies the in vivo immunological environment utilizing intra-vital imaging techniques. These “living window” models allow researchers to observe immune responses during diabetes development or after islet transplantation in real-time.
Dr. Abdulreda’s DRIF funded project entitled “Mechanisms of Islet Transplant Immune Tolerance” aims to understand immune pathways that contribute to graft rejection or immune tolerance. Currently, islet transplantation requires continual immunosuppressive treatment to reduce the chance of islet graft rejection. But long-term immunosuppression gives rise to many complications and can jeopardize the health of the graft and the recipient. Failure of islets to engraft occurs due to immune rejection and other complications associated with routinely used transplantation sites such as the liver. Therefore, new transplantation sites that require little to no immunosuppression are advantageous. Dr. Abdulreda and his team work to establish novel sites and induce immune islet graft tolerance to improve clinical islet transplantation and avoid harmful immunosuppressive therapeutics and their serious complications.
Recently, his team’s proof-of-concept experimentation to achieve immune tolerance was successful in nonhuman preclinical models of islet transplantation. These investigators found that islet transplantation into the anterior chamber of the eye paired with transient mild immune intervention close to transplantation time prolonged islet allograft survival. Immune profiling demonstrated elevated T helper (Th)-2 cytokines suggesting a shift towards immune regulatory functions aiding in the graft immune tolerance . Read more about their recent advances in islet transplant immune tolerant here.
Dr. Abdulreda laboratory’s work elucidates immune mechanisms while harnessing these advances for clinical translation to T1D patients. His team is also exploring islet transplantation into the anterior chamber of the eye as a new transplantation site to treat T1D in humans. His group is spearheading an FDA-approved Phase I clinical trial that is testing this technique in T1D patients. We look forward to seeing the application of Dr. Abdulreda’s groundbreaking research discoveries.
- Abdulreda, Midhat H et al. “Operational immune tolerance towards transplanted allogeneic pancreatic islets in mice and a non-human primate.” Diabetologia vol. 62,5 (2019): 811-821. doi:10.1007/s00125-019-4814-4.