Generation of iPSC-derived insulin-producing cells from patients with type 1 and type 2 diabetes compared with healthy control

Abstract

For alternative sources of β cells, patient-specific induced pluripotent stem cells (iPSCs) could be promising, as cells derived from the "self" allow autologous transplantation. However, only a few studies have investigated insulin-producing cells (IPCs) using iPSCs of patients with type 1 diabetes (T1D). In this study, we generated IPCs using iPSCs derived from patients with T1D and type 2 diabetes (T2D) and compared them with IPCs from a non-diabetic (ND) individual. To facilitate differentiation of human iPSCs into IPCs, we induced PDX-1 gene expression using Ad-PDX-1/VP16. IPCs derived from T1D- and T2D-specific iPSCs expressed islet-specific markers such as Pdx-1, MafA, Beta2/NeuroD, and insulin, similar to IPCs derived from ND-specific iPSCs. In addition, IPCs derived from T1D- and T2D-specific iPSCs showed comparable glucose-stimulated insulin secretion as IPCs derived from ND-specific iPSCs. These results suggest the potential for autologous transplantation using patient-specific iPSCs in patients with T1D and T2D. This study was clinically significant because the majority of people with diabetes have T2D and insulin secretion declines over time in T2D. To the best of our knowledge, this is the first study to generate and simultaneously compare IPCs from ND-, T1D-, and T2D-specific iPSCs.