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Microwell-based pancreas-on-chip model enhances genes expression and functionality of rat islets of Langerhans.
Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2020-06-09 , DOI: 10.1016/j.mce.2020.110892
Amal Essaouiba 1 , Teru Okitsu 2 , Rachid Jellali 3 , Marie Shinohara 4 , Mathieu Danoy 5 , Yannick Tauran 6 , Cécile Legallais 3 , Yasuyuki Sakai 4 , Eric Leclerc 1
Affiliation  

Organ-on-chip technology is a promising tool for investigating physiological in vitro responses in drug screening development, and in advanced disease models. Within this framework, we investigated the behavior of rat islets of Langerhans in an organ-on-chip model. The islets were trapped by sedimentation in a biochip with a microstructure based on microwells, and perfused for 5 days of culture. The live/dead assay confirmed the high viability of the islets in the biochips cultures. The microfluidic culture leads to upregulation of mRNA levels of important pancreatic islet genes: Ins1, App, Insr, Gcgr, Reg3a and Neurod. Furthermore, insulin and glucagon secretion were higher in the biochips compared to the Petri conditions after 5 days of culture. We also confirmed glucose-induced insulin secretion in biochips via high and low glucose stimulations leading to high/low insulin secretion. The high responsiveness of the pancreatic islets to glucagon-like peptide 1 (GLP-1) stimulation in the biochips was reflected by the upregulation of mRNA levels of Gcgr, Reg3a, Neurog3, Ins1, Ins2, Stt and Glp-1r and by increased insulin secretion. The results obtained highlighted the functionality of the islets in the biochips and illustrated the potential of our pancreas-on-chip model for future pancreatic disease modeling and anti-diabetic drugs screening.



中文翻译:

基于微孔的片上胰腺模型可提高朗格罕氏大鼠胰岛的基因表达和功能。

片上器官技术是一种有前途的工具,可用于研究药物筛选开发和高级疾病模型中的生理体外反应。在此框架内,我们研究了器官芯片模型中朗格汉斯大鼠胰岛的行为。通过沉淀将胰岛捕获在具有基于微孔的微结构的生物芯片中,并灌注5天。活/死分析证实了在生物芯片培养物中胰岛的高生存力。微流体培养导致重要的胰岛基因:Ins1AppInsrGcgrReg3aNeurod的mRNA水平上调。此外,与培养5天后的培养皿相比,生物芯片中的胰岛素和胰高血糖素分泌更高。我们还通过高和低葡萄糖刺激导致高/低胰岛素分泌,证实了生物芯片中葡萄糖诱导的胰岛素分泌。GcgrReg3aNeurog3Ins1Ins2SttGlp-1r的mRNA水平上调反映了胰岛对生物芯片中胰高血糖素样肽1(GLP-1)刺激的高响应性并通过增加胰岛素分泌。获得的结果突出了胰岛在生物芯片中的功能,并说明了我们的胰腺芯片模型在未来胰腺疾病建模和抗糖尿病药物筛选中的潜力。

更新日期:2020-06-09
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