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评估人类多能干细胞分化潜能的策略:综述、分析与创新呼吁

Evaluating Strategies to Assess the Differentiation Potential of Human Pluripotent Stem Cells: A Review, Analysis and Call for Innovation.

作者信息

Smith Lucy, Quelch-Cliffe Rebecca, Liu Felicity, Aguilar Alejandro Hidalgo, Przyborski Stefan

机构信息

Department of Biosciences, Durham University, Durham, England.

Reprocell Europe Ltd, NETPark, Sedgefield, England.

出版信息

Stem Cell Rev Rep. 2025 Jan;21(1):107-125. doi: 10.1007/s12015-024-10793-5. Epub 2024 Sep 28.

DOI:10.1007/s12015-024-10793-5
PMID:39340737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11762643/
Abstract

Pluripotent stem cells have the ability to differentiate into all cells and tissues within the human body, and as a result they are attractive resources for use in basic research, drug discovery and regenerative medicine. In order to successfully achieve this application, starting cell sources ideally require in-depth characterisation to confirm their pluripotent status and their ability to differentiate into tissues representative of the three developmental germ layers. Many different methods to assess potency are employed, each having its own distinct advantages and limitations. Some aspects of this characterisation process are not always well standardised, particularly techniques used to assess pluripotency as a function. In this article, we consider the methods used to establish cellular pluripotency and subsequently analyse characterisation data for over 1590 human pluripotent cell lines from publicly available repositories in the UK and USA. In particular, we focus on the teratoma xenograft assay, its use and protocols, demonstrating the level of variation and the frequency with which it is used. Finally, we reflect on the implications of the findings, and suggest in vitro alternatives using modern innovative technology as a way forward.

摘要

多能干细胞具有分化为人体内所有细胞和组织的能力,因此它们是基础研究、药物发现和再生医学中极具吸引力的资源。为了成功实现这一应用,理想情况下起始细胞来源需要进行深入表征,以确认其多能状态以及分化为代表三个发育胚层的组织的能力。人们采用了许多不同的方法来评估细胞的潜能,每种方法都有其独特的优点和局限性。这种表征过程的某些方面并不总是标准化的,特别是用于评估多能性的技术。在本文中,我们考虑了用于建立细胞多能性的方法,并随后分析了来自英国和美国公开存储库的1590多条人类多能细胞系的表征数据。特别是,我们重点关注畸胎瘤异种移植试验、其用途和方案,展示了其变异程度和使用频率。最后,我们思考了这些发现的意义,并建议使用现代创新技术的体外替代方法作为前进的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/0e3488250571/12015_2024_10793_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/3ba96d963bab/12015_2024_10793_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/45ca66af9e80/12015_2024_10793_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/dd4bcea6bdc2/12015_2024_10793_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/77684656c6dc/12015_2024_10793_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/3426dcc00a62/12015_2024_10793_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/0e3488250571/12015_2024_10793_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/3ba96d963bab/12015_2024_10793_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/45ca66af9e80/12015_2024_10793_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/dd4bcea6bdc2/12015_2024_10793_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/77684656c6dc/12015_2024_10793_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/3426dcc00a62/12015_2024_10793_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e449/11762643/0e3488250571/12015_2024_10793_Fig6_HTML.jpg

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2
Epigenetic biomarkers to track differentiation of pluripotent stem cells.胚胎干细胞分化的表观遗传生物标志物。
Stem Cell Reports. 2023 Jan 10;18(1):145-158. doi: 10.1016/j.stemcr.2022.11.001. Epub 2022 Dec 1.
3
Recreating Tissue Structures Representative of Teratomas In Vitro Using a Combination of 3D Cell Culture Technology and Human Embryonic Stem Cells.
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Bioengineering (Basel). 2022 Apr 22;9(5):185. doi: 10.3390/bioengineering9050185.
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An in vitro stem cell model of human epiblast and yolk sac interaction.人胚外内胚层和卵黄囊相互作用的体外干细胞模型。
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