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Title: 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
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  kyouindb  KAKEN_id
Osafune, Kenji
Imagawa, Akihisa
Shimomura, Iichiro
Author's alias: 豊田, 太郎
舩戸, 道徳
近藤, 恭士
須藤, 智美
岸田, 真里菜
岡田, 千尋
渡辺, 亮
浅香, 勲
長船, 健二
Keywords: Fulminant type 1 diabetes
Induced pluripotent stem cell
β‐Cell
Issue Date: May-2018
Publisher: Wiley
Journal title: Journal of Diabetes Investigation
Volume: 9
Issue: 3
Start page: 481
End page: 493
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.
Rights: © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
URI: http://hdl.handle.net/2433/233865
DOI(Published Version): 10.1111/jdi.12727
PubMed ID: 28796422
Appears in Collections:Journal Articles

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