How to make insulin-producing pancreatic β cells for diabetes treatment

Around 400 million people worldwide suffer from diabetes mellitus. The major pathological event for Type 1 diabetes and advanced Type 2 diabetes is loss or impairment of insulin-secreting beta cells of the pancreas. For the past 100 years, daily insulin injection has served as a life-saving treatment for these patients. However, insulin injection often cannot achieve full glucose control, and over time poor glucose control leads to severe complications and mortality. As an alternative treatment, islet transplantation has been demonstrated to effectively maintain glucose homeostasis in diabetic patients, but its wide application is limited by the scarcity of donated islets. Therefore, it is important to define new strategies to obtain functional human beta cells for transplantation therapies. Here, we summarize recent progress towards the production of beta cells in vitro from pluripotent stem cells or somatic cell types including a cells, pancreatic exocrine cells, gastrointestinal stem cells, fibroblasts and hepatocytes. We also discuss novel methods for optimizing beta cell transplantation and maintenance in vivo. From our perspective, the future of beta cell replacement therapy is very promising although it is still challenging to control differentiation of beta cells in vitro and to protect these cells from autoimmune attack in Type 1 diabetic patients. Overall, tremendous progress has been made in understanding beta cell differentiation and producing functional beta cells with different methods. In the coming years, we believe more clinical trials will be launched to move these technologies towards treatments to benefit diabetic patients.