Continuous Inhibition of Sonic Hedgehog Signaling Leads to Differentiation of Human-Induced Pluripotent Stem Cells into Functional Insulin-Producing ? Cells

Human-induced pluripotent stem cell- (iPSC-) derived insulin-producing cells (IPCs) can be used for islet cell transplantation into type 1 diabetic patients and as patient-specific the development of novel antidiabetic drugs. However, a method is needed to generate functional IPCs from iPSCs simplify protocol. We compared combinations small molecules that could induce differentiation definitive endoderm preferentially precursor cells. When generated using an optimal combination molecules, secreted insulin in response glucose stimulation. constructed spheroid optimized culture maturation conditions. Quantitative PCR revealed expression endoderm-specific markers differed depending on molecules. The molecule, N-[(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)methylene]-4-(phenylmethyl)-1-piperazinamine, induced by inhibiting Sonic hedgehog signaling. Images 2D showed formed spheroids day 5 continuously insulin. developed simple produced responded stimulation within relatively short period. posit this along with further refinement process applied clinical trials.