Zilun Wei1, Shuaihua Qiao2, Jinxuan Zhao2, Yihai Liu1, Qiaoling Li2, Zhonghai Wei2, Qing Dai2, Lina Kang2, Biao Xu3. 1. Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China. 2. Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China. 3. Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China. Electronic address: xubiao62@nju.edu.cn.
Abstract
AIMS: The inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury. MAIN METHODS: Computational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy. KEY FINDINGS: miRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury. SIGNIFICANCE: We showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury.
AIMS: The inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury. MAIN METHODS: Computational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy. KEY FINDINGS: miRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury. SIGNIFICANCE: We showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury.
Authors: Yun Lin; Johnathon D Anderson; Lily M A Rahnama; Shenwen V Gu; Anne A Knowlton Journal: Am J Physiol Heart Circ Physiol Date: 2020-09-28 Impact factor: 4.733
Authors: Ricardo Cerqueira de Abreu; Hugo Fernandes; Paula A da Costa Martins; Susmita Sahoo; Costanza Emanueli; Lino Ferreira Journal: Nat Rev Cardiol Date: 2020-06-01 Impact factor: 32.419