Charting Morphotoxicity With Complementary Embryo Models

Dorian Luijkx

doi:10.1002/adhm.202503634

2026-08-28

Clemens van Blitterswijk

Stefan Giselbrecht *

Erik Vrij *

DOI：10.1002/adhm.202503634

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摘要

En 中文

理解发育毒性的需求在于捕捉定义早期人类胚胎发育的完整形态多样性谱系（形态空间）。传统的毒性测试方法依赖动物模型或简化的二维细胞培养，固有的忽视了不同发育阶段和细胞谱系之间微妙的相互作用。为弥补这一差距，我们提出了一种创新的高通量筛选方法，利用三种互补的基于干细胞的3D胚胎模型：植入前阶段的胚状体、早期植入后阶段的类上胚层（EPICs）和类羊膜簇（AMNICs）。这些模型在热成型微孔阵列中培养，并系统地暴露于27种广泛使用的化合物库中。基于图像的自动化分析允许对形态毒性效应进行精确量化。关键发现包括鉴定出抗坏血酸和丙戊酸（VPA）等化合物，它们在不同胚胎模型中表现出独特且相反的作用，突显了发育阶段特异性的敏感性。这一整合平台强调了互补胚胎模型在实现稳健且与人相关的发育毒性评估中的关键作用。

Keyword:

blastoids

postimplantation embryo models

stem cell-based embryo models

thermoformed microwells

toxicity screening

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期刊

Advanced Healthcare Materials

IF:

9.6

论文数:

7.7K

被引数:

4.9W

机构

Maastricht University

学者数:

752

论文数: 293

被引数: 0

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