Matrigel Tunes H9 Stem Cell-Derived Human Cerebral Organoid Development.
Matrigel Tunes H9 Stem Cell-Derived Human Cerebral Organoid Development.
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DOI：
10.3390/organoids2040013
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发表时间：
2023-12
期刊：
影响因子：
--
通讯作者：
Keung AJ
中科院分区：
文献类型：
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作者：
Estridge RC;O'Neill JE;Keung AJ
人类大脑类器官是由人类胚胎干细胞和人类诱导多能干细胞容易产生的，在研究人类神经发育方面很有用。最近对人类大脑类器官的研究探索了不同大脑区域的形成以及可溶性和机械性线索的影响。Matrigel是由恩格尔布雷斯-霍尔姆群小鼠肉瘤细胞分泌的细胞外基质蛋白、形态因子和生长因子的凝胶状异质混合物。它是几乎所有脑类器官方案的核心组成部分，通常支持神经上皮萌芽和组织极化；然而，它在类器官方案中超出一般要求的作用和影响尚未得到很好的理解，其递送方式是可变的，包括类器官的嵌入或以可溶性形式递送。鉴于其广泛使用，我们询问了Matrigel剂量和给药方式如何影响H9干细胞衍生的hCO发育和组成。我们发现Matrigel暴露会影响类器官的大小、形态和细胞类型组成。我们还发现，大量的Matrigel促进脉络膜丛（ChP）细胞数量的增加，这种增加是由BMP4途径调节的。这些结果阐明了Matrigel对人脑类器官发育的影响，以及给药方式和给药量对类器官表型和组成的重要性。
Human cerebral organoids are readily generated from human embryonic stem cells and human induced pluripotent stem cells and are useful in studying human neurodevelopment. Recent work with human cerebral organoids have explored the creation of different brain regions and the impacts of soluble and mechanical cues. Matrigel is a gelatinous, heterogenous mixture of extracellular matrix proteins, morphogens, and growth factors secreted by Engelbreth-Holm-Swarm mouse sarcoma cells. It is a core component of almost all cerebral organoid protocols, generally supporting neuroepithelial budding and tissue polarization; yet, its roles and effects beyond its general requirement in organoid protocols are not well understood, and its mode of delivery is variable, including the embedding of organoids within it or its delivery in soluble form. Given its widespread usage, we asked how H9 stem cell-derived hCO development and composition are affected by Matrigel dosage and delivery method. We found Matrigel exposure influences organoid size, morphology, and cell type composition. We also showed that greater amounts of Matrigel promote an increase in the number of choroid plexus (ChP) cells, and this increase is regulated by the BMP4 pathway. These results illuminate the effects of Matrigel on human cerebral organoid development and the importance of delivery mode and amount on organoid phenotype and composition.