Insulin‐producing cells derived from 'induced pluripotent stem cells' of patients with fulminant type 1 diabetes: Vulnerability to cytokine insults and increased expression of apoptosis‐related genes. Issue 3 (14th September 2017)

• Record Type: Journal Article
• Authors: Hosokawa, Yoshiya; Toyoda, Taro; Fukui, Kenji; Baden, Megu Yamaguchi; Funato, Michinori; Kondo, Yasushi; Sudo, Tomomi; Iwahashi, Hiromi; Kishida, Marina; Okada, Chihiro; Watanabe, Akira; Asaka, Isao; Osafune, Kenji; Imagawa, Akihisa; Shimomura, Iichiro
• Is Part Of: Journal of diabetes investigation. Volume 9:Issue 3(2018)
• Page Start: 481
• Page End: 493
• Publication Date: 2017-09-14
• Subjects: Fulminant type 1 diabetes -- Induced pluripotent stem cell -- β‐Cell; Diabetes -- Periodicals; Diabetes -- Research -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462005
• DOI: 10.1111/jdi.12727
• Languages: English
• ISSNs: 2040-1116

Abstract

Abstract: Aims/Introduction: The present study was carried out to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes, and evaluate the cytokine‐induced apoptotic reactions of β‐like insulin‐producing cells differentiated from the iPSCs. Materials and Methods: iPSCs were generated from fibroblasts of patients with fulminant type 1 diabetes by inducing six reprogramming factors. Insulin‐producing cells were differentiated from the iPSCs in vitro . The proportion of cleaved caspase‐3‐positive or terminal deoxynucleotidyl transferase 2′‐deoxyuridine, 5′‐triphosphate nick end labeling‐positive cells among insulin (INS)‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines was evaluated under treatment with tumor necrosis factor‐α, interleukin‐1β and interferon‐γ. Ribonucleic acid sequencing was carried out to compare gene expressions in INS‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines. Results: Two iPSC clones were established from each of three patients with fulminant type 1 diabetes. The differentiation of insulin‐producing cells from fulminant type 1 diabetes iPSC was confirmed by immunofluorescence analysis and KCl‐induced C‐peptide secretion. After treatment with pro‐inflammatory cytokines, these INS‐positive cells showed higher expression of cleaved caspase‐3 than those derived from control human iPSCs. Altered expression levels of several apoptosis‐related genes were observed in INS‐positive cells derived from the fulminant type 1 diabetes iPSCs by ribonucleic acid sequencing. Conclusions: We generated iPSCs from patients with fulminant type 1 diabetes and differentiated them into insulin‐producing cells. This in vitro disease model can be used to elucidate the disease mechanisms of fulminant type 1 diabetes. Abstract : Proportion of cleaved caspase‐3‐positive cells is high in INS‐positive cells derived from FT1D‐iPSCs after treatment with three cytokines. Our iPSC model should allow for further understanding of the pathophysiology and establishment of therapeutic methods for FT1D.