In Vitro Generation of Glucose-Responsive Insulin-Secreting Cells from Pancreatic and Duodenal Homeobox 1–Overexpressing Human-Induced Pluripotent Stem Cell Derived from Diabetic Patient
Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing transcription factor family, is a key transcription factor for pancreas development and mature β-cell function. In this study, induced overexpression of PDX1 resulted in producing susceptible cells for pancreatic differentiation and was well beneficial to enhance β-cell production, maturation, function, and survival. Induced PDX1 overexpression in harmony with a set of signaling molecules involves in guiding the signaling pathways toward pancreas development, leaded to high-efficient in vitro generation of ectopic insulin-producing cells (IPCs) with the effectively reduced number of polyhormonal cells and increased number of INS single-positive cells. This strategy yielded 85.61% glucose-responsive insulin-positive cells in vitro, which was seven times higher than the basal level, and electron microscopy images revealed the presence of mature β-cell secretory granules. The generation of glucose-responsive insulin-secreting β-like cells from human-induced pluripotent stem cells (hiPSCs) in vitro would provide a promising approach to produce an unprecedented cell source for cell transplantation therapy in diabetes without the ethical obstacle of embryonic stem cells and would bypass immune rejection. These cells are an invaluable source for disease modeling, drug discovery, and pharmacogenomics studies as well.