Generating cells of the gastrointestinal system: current approaches and applications for the differentiation of human pluripotent stem cells

Human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, are defined by their abilities to self-renew and to differentiate into any cell type of the human body. Due to these unique properties, hPSCs represent a potentially unlimited source of cells/tissues for cell replacement therapies. Use of these cells may also revolutionize the way drugs are discovered, designed, and tested. Furthermore, the study of how cells differentiate can also change our understanding of complex human biology and disease. For these reasons, scientists have dedicated significant time and effort to generate specific cell types from hPSCs with therapeutic potential, including cells derived from the definitive endoderm germ layer such as liver cells (hepatocytes) and pancreatic beta cells. In this review, we will focus broadly on the most advanced differentiation strategies currently employed to differentiate hPSCs to endodermal lineages such as the liver, pancreas, and intestine as well as the principles of developmental biology around which these protocols were designed. This will be followed by a brief discussion of the vast potential of these systems as suitable in vitro models for human embryonic development and disease.