Novel Sites for Islet Transplantation

Beta cell replacement therapies, such as islet transplantation, are a growing and effective strategy for restoring glucose regulation in highly selected people with type 1 diabetes. However, limited intrahepatic engraftment, exacerbated by human islet donor heterogenicity, difficulties subverting both allogeneic and autoimmune graft rejection, and the necessity of life long systemic immunosuppression represent significance barriers for its widespread application.

Recent laboratory and clinical advancements in the fields of genetically modified xenografts and stem cell-derived islet like clusters have brought us closer to addressing the shortage of deceased-donor islets while providing a less heterogenous and potentially immuno-evasive source of transplantable insulin-secreting cells. The ability to image, modulate and retrieve the graft in the current liver intraportal space is limited and would be especially important for current efforts to replace deceased-donor islets with these surrogate cells. While rodent and non-human primate preclinical studies show great promise for extrahepatic islet transplantation, clinical experience is limited and compares unfavorably in terms of engraftment, graft function, and glycemic outcomes compared to intraportal islet infusion. It is clear that more optimal transplantation sites and refined methods of improving beta cell graft survival are indispensable to successfully translate these efforts to a clinically relevant approach to islet transplantation.

This research topic focuses on advancing the science of extrahepatic islet transplantation, including novel biomaterials, neovascularization strategies, immune isolation technologies, optimal anatomical implantation approaches, but also investigations involving relevant alternative beta cell sources. Augmenting new transplantation sites with emerging innovations to improve graft function whilst dampening immune activation will critically benefit the future success of beta cell replacement therapies for the broad treatment of diabetes.

We welcome original research and review articles, including but not limited to those, that examine:

• Utility of immune privileged beta cell transplant sites
• Physiological and anatomical characterization of extrahepatic implantation sites
• Development of approaches that enhance cell survival and function in alternative implantation sites
• Modalities that enhance oxygen, nutrients or hormonal kinetics through encapsulation membranes
• Safety of beta cell replacement therapies that do not require chronic immunosuppression
• Novel immuno-isolating strategies to protect beta cell grafts from auto- and allo-immunity
• Localized immunological approaches that delay and/or prevent beta cell graft rejection
• Host factors influencing the success of extrahepatic transplant outcomes

We invite research and review papers focusing basic, preclinical, and clinical studies in the beta cell replacement field. We believe that this research topic within Frontiers in Transplantation will be very timely, scientifically, and clinically innovative, and inspiring.