Developments in endoderm and pancreatic β-cell differentiation from human pluripotent stem cells

Abstract

Human pluripotent stem cells (hPSCs) can differentiate into any cell type in the body, including cells or tissues from ectodermal, mesodermal, or endodermal lineages. Type 1 diabetes is characterized by the selective destruction of β cells in the islets of Langerhans within the pancreas, a process driven by autoimmunity. This destruction leads to the inability to produce and secrete insulin, resulting in poor blood glucose control. Patients with type 1 diabetes require exogenous insulin and regular blood glucose monitoring. However, achieving strict glycemic control solely through this approach is challenging, and there is a risk of side effects such as hypoglycemia when insulin levels rise following exogenous insulin administration. Thus, there is a pressing need for treatments that can overcome these limitations. Stem cell-derived pancreatic β cells are produced through a complex multi-step differentiation process, which involves the application of various growth factors and small molecules to precisely control intracellular signaling pathways at specific times. Our review primarily focused on significant studies concerning the differentiation of hPSCs into highly functional pancreatic β cells, covering key stages of pancreatic development such as definitive endoderm, primitive gut tube, posterior foregut/pancreatic progenitor cells, and pancreatic endocrine cells. Generating insulin-producing functional pancreatic β cells from hPSCs 77could be a viable and renewable cell source for alternative cell therapy to treat type 1 diabetes.