Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USA.
Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
Cells. 2022 Jun 18;11(12):1962. doi: 10.3390/cells11121962.
The development of therapies to prevent or treat salivary gland dysfunction has been limited by a lack of functional in vitro models. Specifically, critical markers of salivary gland secretory phenotype downregulate rapidly ex vivo. Here, we utilize a salivary gland tissue chip model to conduct a design of experiments (DoE) approach to test combinations of seven soluble cues that were previously shown to maintain or improve salivary gland cell function. This approach uses statistical techniques to improve efficiency and accuracy of combinations of factors. The DoE-designed culture conditions improve markers of salivary gland function. Data show that the EGFR inhibitor, EKI-785, maintains relative mRNA expression of Mist1, a key acinar cell transcription factor, while FGF10 and neurturin promote mRNA expression of Aqp5 and Tmem16a, channel proteins involved in secretion. Mist1 mRNA expression correlates with increased secretory function, including calcium signaling and mucin (PAS-AB) staining. Overall, this study demonstrates that media conditions can be efficiently optimized to support secretory function in vitro using a DoE approach.
治疗唾液腺功能障碍的疗法的发展受到缺乏功能性体外模型的限制。具体来说，唾液腺分泌表型的关键标志物在体外迅速下调。在这里，我们利用唾液腺组织芯片模型进行实验设计（DoE）方法，以测试七种可溶性线索的组合，这些线索先前被证明可以维持或改善唾液腺细胞功能。这种方法使用统计技术来提高因素组合的效率和准确性。DoE 设计的培养条件可改善唾液腺功能的标志物。数据表明，EGFR 抑制剂 EKI-785 维持关键腺泡细胞转录因子 Mist1 的相对 mRNA 表达，而 FGF10 和神经生长因子促进参与分泌的通道蛋白 Aqp5 和 Tmem16a 的 mRNA 表达。Mist1 mRNA 表达与增加的分泌功能相关，包括钙信号和粘蛋白（PAS-AB）染色。总的来说，这项研究表明，使用实验设计方法可以有效地优化培养基条件，以支持体外的分泌功能。
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