Cell Replacement Therapy for Insulin-Dependent Diabetes: Maintaining Islet Architecture and Distribution After Graft

Abstract

To survey current practices in clinical islet transplantation to identify the critical factors for designing a successful implant strategy for islets derived from pluripotent stem cells. Of particular importance is the volume of a therapeutic dose and the host sites capable of housing that volume. A calculated dose of surviving islets required for normoglycemia in patients is large, though less than the number of islets present in a healthy pancreas. Great strides have been made developing methods for delivery of a large dose of islets that maintain cell viability and potency. Although many of these endeavor to provide the islets close association to the host vasculature, only some of the strategies maintain the architecture and distribution of the individual islets. The trends in clinical research and in laboratory models suggest that strategies that maintain the architecture and distribution of the individual islets are the most successful. This requirement increases the volume required to deliver a therapeutic dose and limits the anatomical sites available for clinical transplant.