Concise Review: Lessons Learned from Islet Transplant Clinical Trials in Developing Stem Cell Therapies for Type 1 Diabetes

Abstract

We examined data and patterns in clinical islet transplant studies registered on ClinicalTrials.gov (CTgov) for treatment of type 1 diabetes (T1D), with a goal of extracting insights to apply in the design of a pluripotent stem cell-derived islet therapy. Clinical islet transplantation, as a cell therapy (rather than solid organ transplant) is a unique precedent for stem cell-based islet therapies. Registration activity shows that the field is not growing significantly, and newer registrations suggest that the reasons for stagnation include need for a more optimal site of infusion/transplantation, and especially a need for better immune protective strategies to advance a more effective and durable therapy for T1D. Stem Cells Translational Medicine 2019;8:209&214.

Keywords: Hypoglycemia; Immunosuppression; Insulin; Pluripotent stem cells; Transplantation tolerance.

Figure 1

Number of new registrations for islet transplantation clinical trials for type 1 diabetes (y axis) for each year (x axis). Data were obtained by the “Date first posted” notation for each trial.

Figure 2

A vision for the future of islet transplantation. Stem cell‐derived islets, although allogeneic, have the advantages over cadaveric islets of being prequalified during product development, and the transplantation of these islets can be timed to suit the recipient. Because pluripotent stem cell‐derived islets are allogeneic (and will be for the near future because of the expense of generating multiple lines) they will require encapsulation in a device that protects them from the host immune system. The goal of encapsulation is elimination of the need for pharmacologic immunosuppression. The omentum is an optimal site for transplantation because of its rich vascularity and it is amenable to minimally invasive surgery for both implantation and retrieval. Initially inclusion/exclusion criteria for stem cell‐derived islets will be similar to those for cadaveric islet transplantation, until the risks and benefits are better understood. Demonstrated safety and efficacy with stem cell‐derived islets is likely to lead to islet transplantation offered to a larger population of patients with type 1 diabetes than currently treated with cadaveric islets. Source: Copyright free from https://www.dreamstime.com/confirm.php?changeuname=1.