Unit of Molecular Metabolism, Lund University Diabetes Centre, Jan Waldenströms gata 35, Box 50332, SE-202 13 Malmö, Sweden.
Cells. 2020 Nov 12;9(11):2465. doi: 10.3390/cells9112465.
Type 2 diabetes, characterized by dysfunction of pancreatic β-cells and insulin resistance in peripheral organs, accounts for more than 90% of all diabetes. Despite current developments of new drugs and strategies to prevent/treat diabetes, there is no ideal therapy targeting all aspects of the disease. Restoration, however, of insulin-producing β-cells, as well as insulin-responsive cells, would be a logical strategy for the treatment of diabetes. In recent years, generation of transplantable cells derived from stem cells in vitro has emerged as an important research area. Pluripotent stem cells, either embryonic or induced, are alternative and feasible sources of insulin-secreting and glucose-responsive cells. This notwithstanding, consistent generation of robust glucose/insulin-responsive cells remains challenging. In this review, we describe basic concepts of the generation of induced pluripotent stem cells and subsequent differentiation of these into pancreatic β-like cells, myotubes, as well as adipocyte- and hepatocyte-like cells. Use of these for modeling of human disease is now feasible, while development of replacement therapies requires continued efforts.
2 型糖尿病的特征是胰腺β细胞功能障碍和外周器官胰岛素抵抗,占所有糖尿病的 90%以上。尽管目前有新的药物和预防/治疗糖尿病的策略,但针对该疾病的各个方面的理想疗法仍未出现。然而,恢复产生胰岛素的β细胞以及对胰岛素有反应的细胞,将是治疗糖尿病的合理策略。近年来,体外从干细胞中生成可移植细胞已成为一个重要的研究领域。多能干细胞,无论是胚胎来源还是诱导产生的,都是胰岛素分泌和葡萄糖反应细胞的替代和可行来源。尽管如此,持续生成稳健的葡萄糖/胰岛素反应细胞仍然具有挑战性。在这篇综述中,我们描述了诱导多能干细胞的生成的基本概念,以及随后将这些细胞分化为胰腺β样细胞、肌管以及脂肪细胞和肝细胞样细胞的过程。现在已经可以使用这些细胞来模拟人类疾病,而开发替代疗法则需要持续努力。