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

Abstract

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 β 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 β cells for transplantation therapies. Here, we summarize recent progress towards the production of β cells in vitro from pluripotent stem cells or somatic cell types including α cells, pancreatic exocrine cells, gastrointestinal stem cells, fibroblasts and hepatocytes. We also discuss novel methods for optimizing β cell transplantation and maintenance in vivo. From our perspective, the future of β cell replacement therapy is very promising although it is still challenging to control differentiation of β cells in vitro and to protect these cells from autoimmune attack in Type 1 diabetic patients. Overall, tremendous progress has been made in understanding β cell differentiation and producing functional β 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.

Keywords: diabetes mellitus; differentiation; iPSC; insulin; pancreatic β cell; reprogramming; transplantation.