Placenta-on-a-chip: Response of neural cells to pharmaceutical agents transported across the placental barrier

IF 2.4 Q2 ENGINEERING, MULTIDISCIPLINARY
Rajeendra L. Pemathilaka, Nicole N. Hashemi
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Abstract

Striving for sustainable drug discovery, we have presented a proof-of-concept for studying the effects of pharmaceutical agents transported across the placental barrier on neural cells. The potential effects of pharmaceutical agents on fetus have made concerns about their use and require more studies to address these concerns. A placenta-on-a-chip model was fabricated and tested for transport of naltrexone (NTX) and its primary metabolite 6[Formula: see text]-naltrexol. The NTX/6[Formula: see text]-naltrexol transported from the maternal channel to the fetal channel was then collected from the fetal channel. To evaluate the behavior of neural cells following exposure to NTX and 6[Formula: see text]-naltrexol, perfusate from the fetal channel was directed toward the cultured N27 neural cells. Neural cells exposed to the transported NTX/6[Formula: see text]-naltrexol were then evaluated for gene expression and cell viability. Results showed significantly higher fold changes in IL-6 and TNF-[Formula: see text] expression when exposed to NTX/6[Formula: see text]-naltrexol. However, a lower fold change in IL-1[Formula: see text] expression was observed, while it remained the same in sphingosine kinase (sphk)1. Also, cell viability with NTX/6[Formula: see text]-naltrexol exposure was determined to be significantly lower ([Formula: see text]). This study has the potential to reveal the impact of pharmaceutical agents on the developing neural system of fetuses and their premature brains.
胎盘芯片:神经细胞对通过胎盘屏障运输的药物的反应
为了可持续的药物发现,我们提出了一个概念验证,用于研究药物通过胎盘屏障运输对神经细胞的影响。药物制剂对胎儿的潜在影响引起了人们的关注,需要更多的研究来解决这些问题。制作胎盘芯片模型并检测纳曲酮(NTX)及其主要代谢物6 -纳曲醇的转运。NTX/6[公式:见文]-纳曲醇从母体通道转运到胎儿通道,然后从胎儿通道收集。为了评估神经细胞暴露于NTX和6 -纳曲醇后的行为,将胎儿通道的灌注液导向培养的N27神经细胞。神经细胞暴露于运输的NTX/6[公式:见文本]-纳曲醇,然后评估基因表达和细胞活力。结果显示,暴露于NTX/6[公式:见文本]-纳曲醇时,IL-6和TNF-表达的倍数变化显著升高。然而,IL-1[公式:见文]的表达变化较低,而鞘氨酸激酶(sphk)1的表达保持不变。此外,NTX/6[公式:见文本]-纳曲醇暴露的细胞活力被确定为显着降低([公式:见文本])。这项研究有可能揭示药物对胎儿发育中的神经系统和早产儿大脑的影响。
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