Replacing and safeguarding pancreatic β cells for diabetes

For almost a century, insulin replacement has been achieved through daily injections of insulin matched to meals. With close to 400 million people afflicted with diabetes, this therapy is now a multibillion-dollara-year industry. Although life-sustaining, exogenous insulin replacement does not adequately control glycemia or prevent the sequelae of debilitating complications, including retinopathy, nephropathy, neuropathy, and enhanced risk of cardiovascular disease. Recent progress has focused attention on therapies designed to restore appropriately regulated insulin production within the body by regenerating endogenous pancreatic beta cells or implanting an exogenous source of beta cells into patients. Pluripotent stem cell-derived pancreatic progenitor cells, which undergo the final stages of beta cell development in vivo, are currently being tested clinically, and recently, insulin-secreting cells with attributes of mature beta cells, including glucose-responsiveness, have been produced in culture. In parallel, scientists are developing ways to protect replaced beta cells from destruction by the immune system. Here, we discuss recent progress toward a cell-based therapy for diabetes and our perspectives on the future of beta cell replacement.