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多能干细胞作为疾病建模和糖尿病细胞治疗的潜在工具。

Pluripotent stem cells as a potential tool for disease modelling and cell therapy in diabetes.

机构信息

Qatar Biomedical Research Institute, Qatar Foundation, Education City, 5825, Doha, Qatar,

出版信息

Stem Cell Rev Rep. 2014 Jun;10(3):327-37. doi: 10.1007/s12015-014-9503-6.

Abstract

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.

摘要

糖尿病是全球发病率呈上升趋势的最普遍疾病。迄今为止,糖尿病的发病机制还远未被理解,也没有根治糖尿病的方法。了解和治疗糖尿病的一个很有前途的方法是使用多能干细胞(PSCs),包括胚胎干细胞(ESCs)和诱导多能干细胞(iPSCs)。ESCs 和 iPSCs 具有分化为所有细胞类型的巨大潜力,并且具有高度分化为胰岛素分泌β细胞的能力。获得与患有糖尿病的患者基因相同的 PSCs,一直是体外疾病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。然而,这项技术面临着伦理和实际问题的困扰。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,包括没有伦理问题和没有免疫排斥的风险。最近已经从不同类型的糖尿病患者中生成了几种 iPSC 系,其中大多数细胞系能够分化为胰岛素分泌β细胞。在这篇综述中,我们总结了 PSCs 向胰腺β细胞分化的最新进展,并描述了它们在糖尿病细胞治疗中的临床应用所面临的挑战。此外,我们还讨论了使用患者特异性 PSCs 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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