Human Heart Anoxia and Reperfusion Tissue (HEART) Model for the Rapid Study of Exosome Bound miRNA Expression As Biomarkers for Myocardial Infarction

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 18; no. 28; pp. e2201330 - n/a
• Main Authors: Ellis, Bradley W., Ronan, George, Ren, Xiang, Bahcecioglu, Gokhan, Senapati, Satyajyoti, Anderson, David, Handberg, Eileen, March, Keith L., Chang, Hsueh‐Chia, Zorlutuna, Pinar
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.07.2022
• Subjects: Anoxia; biomarker discovery; Biomarkers; Biomarkers - metabolism; Biosensors; Blood plasma; cardiac tissue engineering; Cell death; Diagnosis; Endothelial cells; Endothelial Cells - metabolism; Exosomes - metabolism; Heart attacks; heart‐on‐chip; Humans; Hypoxia - metabolism; Induced Pluripotent Stem Cells - metabolism; Ischemia; MicroRNAs; MicroRNAs - metabolism; Myocardial infarction; Myocardial Infarction - diagnosis; Myocardial Infarction - pathology; myocardial infarction models; Myocytes, Cardiac - metabolism; Nanotechnology; Reperfusion; Reperfusion Injury - diagnosis; Stem cells; microRNAs; cardiac tissue engineering; myocardial infarction models; biomarker discovery; heart-on-chip
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202201330

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 the human cardiac miRNA profile during MI is extremely difficult. Here, to study the changes in miRNA levels during acute MI, 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, is developed. This model is exposed to anoxia followed by normoxia to mimic ischemia and reperfusion, respectively. Using a highly sensitive miRNA biosensor that the authors developed, 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, is shown. 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, is also shown. Hence, the MI‐on‐chip model developed here can be used in biomarker discovery. In this study, a tissue‐engineered human heart anoxia and reperfusion tissue (HEART) model is 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 is also observed that the HEART has comparable miRNA concentrations and exosome profiles to time matched clinical samples.