Advances in β cell replacement and regeneration strategies for treating diabetes

In the past decade, new approaches have been explored that are aimed at restoring functional beta cell mass as a treatment strategy for diabetes. The two most intensely pursued strategies are beta cell replacement through conversion of other cell types and beta cell regeneration by enhancement of beta cell replication. The approach closest to clinical implementation is the replacement of beta cells with human pluripotent stem cell-derived (hPSC-derived) cells, which are currently under investigation in a clinical trial to assess their safety in humans. In addition, there has been success in reprogramming developmentally related cell types into beta cells. Reprogramming approaches could find therapeutic applications by inducing beta cell conversion in vivo or by reprogramming cells ex vivo followed by implantation. Finally, recent studies have revealed novel pharmacologic targets for stimulating beta cell replication. Manipulating these targets or the pathways they regulate could be a strategy for promoting the expansion of residual beta cells in diabetic patients. Here, we provide an overview of progress made toward beta cell replacement and regeneration and discuss promises and challenges for clinical implementation of these strategies.