Genetic engineering approaches in stem and somatic cells for the generation of insulin-producing β-cells

Cell replacement therapies hold great promise for the treatment of type 1 diabetes mellitus; however, the obtaining of sufficient transplantable β-cells limits the availability of this treatment option. The generation of β-cells from human pluripotent stem cells or other somatic cells through classical differentiation, forward programming, or transdifferentiation approaches offers an alternative source of therapeutic β-cells for the treatment of type 1 diabetes mellitus. Through increasing understanding of pancreatic and β-cell development, transcription factors neurogenin 3 (NGN3), pancreas/duodenum homeobox protein 1 (PDX1), and MAF BZIP Transcription Factor A (MAFA) have been identified to be crucial for glucose-responsive insulin secretion of adult β-cells. In this review, we address and discuss recent advances in transdifferentiation approaches using these three markers for the timely generation of mature β-cells, and the insights they provide on cell development and plasticity.