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Pluripotent Stem Cells as a Potential Tool for Disease Modelling and Cell Therapy in Diabetes

机译:多能干细胞作为糖尿病疾病建模和细胞治疗的潜在工具

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Diabetes mellitus is the most prevailing disease with progressive incidence worldwide. To date, the pathogenesis of diabetes is far to be understood, and there is no permanent treatment available for diabetes. One of the promising approaches to understand and cure diabetes is to use pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs). ESCs and iPSCs have a great potential to differentiate into all cell types, and they have a high ability to differentiate into insulin-secreting β cells. Obtaining PSCs genetically identical to the patient presenting with diabetes has been a longstanding dream for the in vitro modeling of disease and ultimately cell therapy. For several years, somatic cell nuclear transfer (SCNT) was the method of choice to generate patient-specific ESC lines. However, this technology faces ethical and practical concerns. Interestingly, the recently established iPSC technology overcomes the major problems of other stem cell types including the lack of ethical concern and no risk of immune rejection. Several iPSC lines have been recently generated from patients with different types of diabetes, and most of these cell lines are able to differentiate into insulin-secreting β cells. In this review, we summarize recent advances in the differentiation of pancreatic β cells from PSCs, and describe the challenges for their clinical use in diabetes cell therapy. Furthermore, we discuss the potential use of patient-specific PSCs as an in vitro model, providing new insights into the pathophysiology of diabetes.
机译:糖尿病是最流行的疾病,在世界范围内具有渐进的发病率。迄今为止,糖尿病的发病机理尚不清楚,并且没有针对糖尿病的永久治疗。了解和治愈糖尿病的一种有前途的方法是使用多能干细胞(PSC),包括胚胎干细胞(ESC)和诱导型PCS(iPSC)。 ESC和iPSC具有分化成所有细胞类型的巨大潜力,并且它们具有分化成分泌胰岛素的β细胞的高能力。获得与糖尿病患者在基因上相同的PSC,一直是疾病体外建模和最终细胞治疗的长期梦想。多年来,体细胞核移植(SCNT)是生成患者特异性ESC系的首选方法。但是,该技术面临道德和实践问题。有趣的是,最近建立的iPSC技术克服了其他干细胞类型的主要问题,包括缺乏道德上的关注和没有免疫排斥的风险。最近已经从患有不同类型的糖尿病的患者中产生了几种iPSC细胞系,并且这些细胞系中的大多数能够分化为分泌胰岛素的β细胞。在这篇综述中,我们总结了胰腺β细胞从PSCs分化中的最新进展,并描述了其在糖尿病细胞治疗中临床应用的挑战。此外,我们讨论了患者特异性PSC作为体外模型的潜在用途,为糖尿病的病理生理学提供了新的见解。

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