Abstract P1094: Mesenchymal Stem Cells Educate Lung Megakaryocytes To Favor Cardiac Repair Post Myocardial Infarction

Abstract

Stem cell therapy in myocardial infarction (MI) have mixed clinical results, and the mechanism of its potential benefits is uncertain. Intravenously administrated mesenchymal stem cells (MSCs) are trapped in the lung capillary bed and hardly reach to the heart. Despite their extremely low retention in the heart, cardiac repair benefits are still seen in multiple clinical trials. There is a large knowledge gap exists regarding the interconnection and bidirectional pathways between heart and lung. It has been established that lung is a reservoir of megakaryocytes (MKs), which produce platelets. We found that MSCs trapped in the lung capillary altered the transcription profiles of lung MKs and circulating platelets. Single cell analysis revealed that MSCs reduced the activation of megakaryocyte progenitor cells (MKp) and promoted MK maturation in the lung. Additionally, MSC treatment reduced the activation of immune cells and the ratio of proinflammatory monocytes in the lung and macrophage infiltration in the infarcted area. CellChat analysis demonstrated that reduced communication between lymphocytes and MKp after MSC treatment. Lastly, we demonstrated that cell-cell contact was needed for this education process, and MSC secretome didn’t promote the megakaryopoiesis process in vitro and in vivo . Intravenously injection of MSCs showed a better therapeutic effect compared to MSC secretome in MI mice. Collectively, this study unevils the role of pulmonary MK in lung-heart crosstalk and the interaction of MSCs trapped in the lung tissue with pulmonary MK during MI. Scheme 1. Schematic illustration of heart-lung crosstalk and the role of lung MK during MI.