Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Exp Clin Endocrinol Diabetes. 2020 May;128(5):339-346. doi: 10.1055/a-0661-5873. Epub 2018 Aug 16.
Diabetes type 1 (T1D) is a common autoimmune disease characterized by permanent destruction of the insulin-secreting β-cells in pancreatic islets, resulting in a deficiency of the glucose-lowering hormone insulin and persisting high blood glucose levels. Insulin has to be replaced by regular subcutaneous injections, and blood glucose level must be monitored due to the risk of hyperglycemia. Recently, transplantation of new pancreatic β-cells into T1D patients has come to be considered one of the most potentially effective treatments for this disease. Therefore, much effort has focused on understanding the regulation of β-cells. Induced pluripotent stem cells (iPSCs) represent a valuable source for T1D modelling and cell replacement therapy because of their ability to differentiate into all cell types . Recent advances in stem cell-based therapy and gene-editing tools have enabled the generation of functionally adult pancreatic β-cells derived from iPSCs. Although animal and human pancreatic development and β-cell physiology have significant differences, animal models represent an important tool in evaluating the therapeutic potential of iPSC-derived β-cells on type 1 diabetes treatment. This review outlines the recent progress in iPSC-derived β-cell differentiation methods, disease modelling, and future perspectives.
1 型糖尿病(T1D)是一种常见的自身免疫性疾病,其特征是胰岛中胰岛素分泌β细胞的永久性破坏,导致降低血糖的激素胰岛素缺乏,并持续存在高血糖水平。由于存在高血糖的风险,必须通过定期皮下注射来补充胰岛素,并且必须监测血糖水平。最近,将新的胰岛β细胞移植到 T1D 患者中已被认为是该疾病最有潜力的有效治疗方法之一。因此,人们致力于了解β细胞的调节。诱导多能干细胞(iPSCs)由于能够分化为所有细胞类型,代表了 T1D 建模和细胞替代治疗的有价值的来源。基于干细胞的治疗和基因编辑工具的最新进展使能够从 iPSCs 中产生具有功能的成人胰腺β细胞。尽管动物和人类的胰腺发育和β细胞生理学有很大的差异,但动物模型是评估 iPSC 衍生的β细胞在 1 型糖尿病治疗中的治疗潜力的重要工具。本文综述了 iPSC 衍生β细胞分化方法、疾病建模以及未来展望的最新进展。