Human Heart Anoxia and Reperfusion Tissue (HEART) Model for the Rapid Study of Exosome Bound miRNA Expression As Biomarkers for Myocardial Infarction.
Human Heart Anoxia and Reperfusion Tissue (HEART) Model for the Rapid Study of Exosome Bound miRNA Expression As Biomarkers for Myocardial Infarction.
复制标题
人心脏缺氧和再灌注组织（心脏）模型，以快速研究外泌体miRNA表达作为心肌梗塞的生物标志物。
DOI：
10.1002/smll.202201330
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发表时间：
2022-07
期刊：
影响因子：
13.3
通讯作者：
Zorlutuna, Pinar
中科院分区：
文献类型：
--
作者：
Ellis, Bradley W.;Ronan, George;Ren, Xiang;Bahcecioglu, Gokhan;Senapati, Satyajyoti;Anderson, David;Handberg, Eileen;March, Keith L.;Chang, Hsueh-Chia;Zorlutuna, Pinar
关键词：
目前用于心肌梗死(MI)诊断的生物标志物通常是细胞死亡后释放的晚期标志物，不能区分缺血和再灌注损伤，并且可以是其他病理的症状。最近，循环microRNAs(MiRNAs)被认为是诊断MI的替代生物标志物，然而，检测MI期间人类心脏miRNA谱的变化是极其困难的。在这里，为了研究急性心肌梗死期间miRNA水平的变化，我们建立了一个具有心脏通道和血管通道的芯片上模型，其中心脏通道包含人诱导多能干细胞(HiPSC)来源的人心脏脱细胞基质和胶原中的心肌细胞，血管通道包含hiPSC来源的内皮细胞。我们将该模型暴露在缺氧和常氧环境中，分别模拟缺血和再灌流。使用我们开发的高灵敏度miRNA生物传感器，我们显示在MI-on-Chip和在缺血和再灌注前后收集的时间匹配的人血浆样本中miR-1、miR-208B和miR-499水平完全相同地增加。我们还发现，工程模型中外切体的表面标记谱随缺血和再灌注损伤的反应而变化，可作为检测心肌梗死的生物标记。因此，我们在这里开发的芯片上MI模型可以用于生物标记物的发现。在这项研究中，我们建立了一个组织工程化的人心脏缺氧和再灌注组织(心脏)模型，并结合一个接近实时的miRNA浓度传感器来测试miRNAs作为新的心脏病发作生物标志物的可行性。作为概念的证明，还观察到心脏具有与时间匹配的临床样本类似的miRNA浓度和外切体谱。
Current biomarkers for myocardial infarction (MI) diagnosis are typically late markers released upon cell death, incapable of distinguishing between ischemic and reperfusion injury, and can be symptoms of other pathologies. Circulating microRNAs (miRNAs) have recently been proposed as alternative biomarkers for MI diagnosis; however, detecting the changes in human cardiac miRNA profile during MI is extremely difficult. Here, to study the changes in miRNA levels during acute MI, we develop a heart-on-chip model with a cardiac channel, containing human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes in human heart decellularized matrix and collagen, and a vascular channel, containing hiPSC-derived endothelial cells. We exposed this model to anoxia followed by normoxia to mimic ischemia and reperfusion, respectively. Using a highly sensitive miRNA biosensor that we developed, we show the exact same increase in miR-1, miR-208b, and miR-499 levels in the MI-on-chip and the time-matched human blood plasma samples collected before and after ischemia and reperfusion. We also show that the surface marker profile of exosomes in the engineered model changes in response to ischemic and reperfusion injury, which can be used as biomarkers to detect MI. Hence, the MI-on-chip model we develop here can be used in biomarker discovery. In this study, a tissue engineered Human Heart Anoxia and Reperfusion Tissue (HEART) model was developed and combined with a near real-time miRNA concentration sensor to test the viability of miRNAs as novel heart attack biomarkers. As a proof of concept, it was also observed that the HEART had comparable miRNA concentrations and exosome profiles to time matched clinical samples.
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