Estridge R Chris, O'Neill Jennifer E, Keung Albert J
Department of Chemical & Biomolecular Engineering, North Carolina State University, Raleigh, NC 27606, USA.
Genetics Program, Department of Biological Sciences, North Carolina State University, Raleigh, NC 27606, USA;
Organoids. 2023 Dec;2(4):165-176. doi: 10.3390/organoids2040013. Epub 2023 Oct 5.
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.
人源大脑类器官很容易从人胚胎干细胞和人诱导多能干细胞中生成，并且在研究人类神经发育方面很有用。最近关于人源大脑类器官的研究探索了不同脑区的创建以及可溶性和机械信号的影响。基质胶是一种由恩格尔布雷特-霍尔姆-斯旺小鼠肉瘤细胞分泌的细胞外基质蛋白、形态发生素和生长因子的凝胶状异质混合物。它是几乎所有大脑类器官培养方案的核心成分，通常支持神经上皮出芽和组织极化；然而，其在类器官培养方案中超出一般需求的作用和影响尚未得到充分理解，其递送方式也各不相同，包括将类器官包埋在其中或以可溶形式递送。鉴于其广泛应用，我们探究了基质胶的剂量和递送方法如何影响源自H9干细胞的人源大脑类器官的发育和组成。我们发现基质胶的接触会影响类器官的大小、形态和细胞类型组成。我们还表明，更多量的基质胶会促进脉络丛（ChP）细胞数量的增加，并且这种增加受BMP4信号通路调控。这些结果阐明了基质胶对人源大脑类器官发育的影响以及递送方式和量对类器官表型和组成的重要性。
