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从人类多能干细胞到功能性胰腺β细胞的艰难旅程。

An arduous journey from human pluripotent stem cells to functional pancreatic β cells.

机构信息

Programme in Stem Cell, Regenerative Medicine and Ageing, Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Singapore, Singapore.

School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

出版信息

Diabetes Obes Metab. 2018 Jan;20(1):3-13. doi: 10.1111/dom.12996. Epub 2017 Jun 7.

Abstract

Type 1 and type 2 diabetes are caused by a destruction and decrease in the number of functional insulin-producing β cells, respectively; therefore, the generation of functional β cells from human embryonic stem cells and human induced pluripotent stem cells, collectively known as human pluripotent stem cells (hPSCs), for potential cell replacement therapy and disease modelling is an intensely investigated area. Recent scientific breakthroughs enabled derivation of large quantities of human pancreatic β-like cells in vitro, although with varied glucose-stimulated insulin secretion kinetics. In the present review, we comprehensively summarize, compare and critically analyze the intricacies of these developing technologies, including differentiation platforms, robustness of protocols, and methodologies used to characterize hPSC-derived β-like cells. We also discuss experimental issues that need to be resolved before these β-like cells can be used clinically.

摘要

1 型和 2 型糖尿病分别由功能性胰岛素分泌β细胞的破坏和数量减少引起;因此,从人胚胎干细胞和人诱导多能干细胞(统称为人多能干细胞,hPSC)中产生功能性β细胞,用于潜在的细胞替代治疗和疾病建模,是一个受到广泛研究的领域。最近的科学突破使得能够在体外大量衍生出人类胰腺β样细胞,但葡萄糖刺激胰岛素分泌动力学存在差异。在本综述中,我们全面总结、比较和批判性分析了这些不断发展的技术的复杂性,包括分化平台、方案的稳健性以及用于鉴定 hPSC 衍生β样细胞的方法。我们还讨论了在这些β样细胞能够临床应用之前需要解决的实验问题。

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