Graphene oxide (GO) has several potential biomedical applications and therefore cytotoxic evaluation of GO is very important. However, the two most common in vitro models for testing cytotoxicity—primary human cells and immortalized cell lines—suffer serious limitations, namely limited supplies of cells and unrealistic cellular responses, respectively. Here, we demonstrate the use of embryonic stem cell (ESC)‐derived cells to study GO cytotoxicity. We tested the use of retinal pigment epithelium (RPE) cells derived from three‐dimensional human ESC cultures (“ESC‐RPE” cells) as a model of GO cytotoxicity by exposing them to varying concentrations of GO nanosheets. For comparison, we also performed the same test with primary human retinal pigment epithelium cells (“hRPE”), and with cells derived from a human RPE cell line (“ARPE19” cells). We found that cytotoxicity metrics (viability, apoptosis, intracellular reactive oxygen species, and mitochondrial membrane potential) were very similar in ESC‐RPE cells and hRPE cells, and those in ARPE19 cells were very different. We conclude that cell models of GO cytotoxicity derived from ESCs are an excellent alternative to primary human cells, without the limitations of tissue availability.

中文翻译：

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使用胚胎干细胞衍生细胞评估氧化石墨烯的细胞毒性。

氧化石墨烯 (GO) 具有多种潜在的生物医学应用，因此对 GO 的细胞毒性评估非常重要。然而，用于测试细胞毒性的两种最常见的体外模型——原代人类细胞和永生化细胞系——受到严重的限制，分别是细胞供应有限和不切实际的细胞反应。在这里，我们展示了使用胚胎干细胞 (ESC) 衍生的细胞来研究 GO 细胞毒性。我们通过将来自三维人类 ESC 培养物（“ESC-RPE”细胞）的视网膜色素上皮 (RPE) 细胞暴露于不同浓度的 GO 纳米片中，测试了它们作为 GO 细胞毒性模型的使用。为了进行比较，我们还对原代人视网膜色素上皮细胞（“hRPE”）和源自人 RPE 细胞系的细胞（“ARPE19”细胞）进行了相同的测试。我们发现 ESC-RPE 细胞和​​ hRPE 细胞的细胞毒性指标（活力、细胞凋亡、细胞内活性氧和线粒体膜电位）非常相似，而在 ARPE19 细胞中的指标则非常不同。我们得出结论，源自 ESC 的 GO 细胞毒性细胞模型是原代人类细胞的绝佳替代品，没有组织可用性的限制。