The Joint JDRF NIH Workshop on Beta Cell Replacement Therapies in T1D took place at the NIH Campus on May 18-19, 2022. The goal of the workshop was to discuss how to accelerate the clinical development of beta cell therapies in T1D. Speakers and panelists from the regulatory, industrial, clinical and research sectors provided their prospective on the topic. Dr. Albert J. Hwa, Program Director of the NIH NIDDK Division of Diabetes, Endocrinology and Metabolic Diseases and Dr. Alice Tomei, Associate Professor of Biomedical Engineering at the University of Miami and Diabetes Research Institute summarized the main topics discussed below.

Improved technologies to provide more precise engineering of the materials and devices for beta cell replacement were discussed. Overall, more attention is now paid to scaling up and CMC of beta cell production, as well as ways to characterize the heterogenous cell populations in stem cell-derived islets as replenishable sources of beta cells to replace cadaveric islets. Increasing combinations of the cells within devices were presented, including some strategies that take advantage of the wound healing response to establish prevascularized sites for beta cell delivery. A multitude of approaches to improve the engraftment efficiency at extrahepatic sites and to minimize the use of immunosuppression to prevent rejection and recurrence of autoimmunity after transplantation of allogenic beta cells were presented. And this included the exciting development in genetic engineering of human stem cells and porcine islets to reduce immunogenicity and increasing safety of the beta cell product. As we increase the complexity of the beta cell product, productive discussions on useful preclinical models to help inform the assessment of biocompatibility, safety, integration with the host and cell function after cell transplantation were discussed. Challenges in selecting preclinical models to predict human host responses before initiating trials in patients were highlighted indicating the ongoing work to evaluate such new research approaches for translation. FDA speakers discussed the regulatory framework for testing these novel products in humans. The patient panel discussion informed the attendees on why we are all here to move toward a goal of widely applicable beta cell therapy with excitement towards new therapies. A summary of the experience of CIT trials and the exciting development of new stem cell derived products now in clinical testing were also provided. Better tools to evaluate and stratify patients, for qualifying inclusions and to have better trial outcome measures, and innovative clinical trial designs are now available to improve future trials. With the continuing improvement in diabetes care, careful considerations on clinical trial design especially for the new products entering clinical testing need to be made. Overall, the workshop indicates that we are really at an exciting time to see translation to move beta cell replacement research from bench to bedside, fostered by increasing multidisciplinary collaborations, and certainly a ton of progress has been made since the last meeting in 2009.