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

The Feasibility and Applicability of Stem Cell Therapy for the Cure of Type 1 Diabetes

“…Millman et al reported that there were no differences between T1D and non-diabetes SC-islet cells in response to cytokine-induced stress, such as changes in interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), or interferon-γ (INF-γ) [ 42 ]. SC-islet cells from T1D and type 2 diabetes (T2D) patients reportedly showed insulin secretion comparable to that of SC-islet cells from non-diabetic subjects [ 43 ]. On the other hand, Hosokawa et al reported that when SC-islet cells from patients with fulminant T1D and healthy subjects were treated with inflammatory cytokines (TNF-α, IL-1β and IFN-γ), apoptosis was more likely to occur in the SC-islet cells from the fulminant T1D subjects [ 44 ].…”

“…Under 20 mM high glucose stimulation, iPSCs-derived islets generated from T1D patients showed insulin secretion similar to that of iPSCs-derived islets generated from non-diabetic patients, indicating glucose-dependent insulin secretion (2.0 ± 0.4 vs. 1.9 ± 0.3 mIU/10 3 cells) [ 42 ]. Kim et al generated iPSCs-derived insulin-secreting cells from T1D and T2D subjects and compared them with those from healthy controls, and each derived cell secreted insulin dependent on the blood glucose levels [ 43 ]. It is a physical and psychological burden for T1D patients to have to measure their blood glucose level and inject insulin every time they eat, but stem cell therapy can free T1D patients from blood glucose monitoring and insulin injection.…”

Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

“…Multiple iPSCs from T1D and T2D patients have been made (148)(149)(150)(151), and there are consortia and foundations that are focused on making larger banks of available diabetes and non-diabetes iPSC lines, including the Human Islet Research Network (HIRN, https:// hirnetwork.org/hpap-overview) and the New York Stem Cell Foundation (NYSCF, https://nyscf.org/research-institute/ repository-stem-cell-search/). Several groups have also recently performed lab-directed differentiations on patient-derived iPSC lines to generate stem cell derived b-cells to examine broad molecular and functional differences (150,151). Unlike the need for the generation of isogenic lines in the study of monogenic diabetes, making banks of T1D, T2D, and non-diabetic stem cell derived b-cells can be used to study many factors contributing to b-cell pathophysiology in diabetes.…”

“…In order to understand the role of these variants, iPSC banks from T1D, T2D and non-diabetic patients can be used to probe these differences on a multigene scale. Multiple iPSCs from T1D and T2D patients have been made ( 148 – 151 ), and there are consortia and foundations that are focused on making larger banks of available diabetes and non-diabetes iPSC lines, including the Human Islet Research Network (HIRN, ) and the New York Stem Cell Foundation (NYSCF, ). Several groups have also recently performed lab-directed differentiations on patient-derived iPSC lines to generate stem cell derived β-cells to examine broad molecular and functional differences ( 150 , 151 ).…”

Human Pluripotent Stem Cells Go Diabetic: A Glimpse on Monogenic Variants

“…Although iPSC could be successfully generated from T1D and T2D patients, complex autoimmune reactions, environmental influence, as well as multifactorial genetic factors hampered the intimate recapitulation of pathogenesis (162)(163)(164). Despite the complexity of T1D and T2D pathogenesis, some recent approaches have been performed to model T1D using pluripotent stem cells.…”