Generating pancreatic beta-like cells from human pluripotent stem cells

Diabetes is a major healthcare burden globally, affecting over 463 million people today, according to the International Diabetes Federation. The most common types of diabetes are Type I diabetes (T1D) and Type II diabetes (T2D), characterized by hyperglycemia due to autoimmune destruction of β cells (T1D) and β cell dysfunction, usually on a background of insulin resistance (T2D). There is currently no cure for diabetes, and patients with T1D require lifelong insulin therapy. Additionally, while most cases of T2D can be managed by lifestyle and diet modifications, with or without antidiabetic drugs, severe cases of T2D may also require insulin therapy. The only means to restore stable euglycemia in these patients is now via whole pancreas or islet transplantation. However, this is limited by the scarcity of donors. In recent years, advances in human pluripotent stem cell (hPSC) technologies and pancreatic β cell differentiation protocols have opened up new potential avenues for cell replacement therapies for diabetes. These advances have also created opportunities to use hPSC-derived β-like cells for studies of disease mechanisms and drug discovery, which in turn have the potential to lead to better therapies for diabetes patients. Here, we describe the protocol used in our laboratory to generate β-like cells from hPSCs to study the mechanisms underlying various types of diabetes.