Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury

Abstract

BackgroundThe acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier resulting in accumulation of proteinaceous edema and increased inflammatory cells in the alveolar space. We previously found that endothelial progenitor cell (EPC) exosomes prevent endothelial dysfunction and lung injury in sepsis in part due to their encapsulation of miRNA-126. However, the effects of EPC exosomes in acute lung injury (ALI) remain unknown.MethodsTo determine if EPC exosomes would have beneficial effects in ALI, intratracheal administration of lipopolysaccharide (LPS) was used to induce ALI in mice. Lung permeability, inflammation, and the role of miRNA-126 in the alveolar-epithelial barrier function were examined.ResultsThe intratracheal administration of EPC exosomes reduced lung injury following LPS-induced ALI at 24 and 48 h. Compared to placebo, intratracheal administration of EPC exosomes significantly reduced the cell number, protein concentration, and cytokines/chemokines in the bronchoalveolar lavage fluid (BALF), indicating a reduction in permeability and inflammation. Further, EPC exosomes reduced myeloperoxidase (MPO) activity, lung injury score, and pulmonary edema, demonstrating protection against lung injury. Murine fibroblast (NIH3T3) exosomes, which do not contain abundant miRNA-126, did not provide these beneficial effects. In human small airway epithelial cells (SAECs), we found that overexpression of miRNA-126-3p can target phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), while overexpression of miRNA-126-5p inhibits the inflammatory alarmin HMGB1 and permeability factor VEGFα. Interestingly, both miR-126-3p and 5p increase the expression of tight junction proteins suggesting a potential mechanism by which miRNA-126 may mitigate LPS-induced lung injury.ConclusionsOur data demonstrated that human EPC exosomes are beneficial in LPS-induced ALI mice, in part through the delivery of miRNA-126 into the injured alveolus.Electronic supplementary materialThe online version of this article (10.1186/s13054-019-2339-3) contains supplementary material, which is available to authorized users.

YBX-1 mediated sorting of miR-133 into hypoxia/reoxygenation-induced EPC-derived exosomes to increase fibroblast angiogenesis and MEndoT

“…Furthermore, exosomes had been shown to carry different nucleic acids, including microRNAs (miRNAs), which are acquired by recipient cells to regulate their own fate [10,11]. Previous studies found that miRNAs in exosomes from endothelial progenitor cells improved outcomes of patients with cardiovascular disease [12] and lipopolysaccharide-induced acute lung injury [13] and also of a murine model of sepsis [12].…”

Exosomes from Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorate Histone-Induced Acute Lung Injury by Activating the PI3K/Akt Pathway in Endothelial Cells.

“…Although the mechanisms underlying histone-related endothelial cytotoxicity are not fully understood, it has been reported that histones can cause direct endothelial cytotoxicity by integrating into the phospholipid bilayer of cell membranes, altering their permeability, thus resulting in an in ux of calcium ions and cell death [17,37,38]. Histones also interact with Toll-like receptors (TLRs) and proin ammatory cytokine/chemokine, released through MyD88, NFκB, and NLRP3 in ammasomedependent pathways [17,21].…”

Increased mobilization of mesenchymal stem cells in patients with acute respiratory distress syndrome undergoing extracorporeal membrane oxygenation

“…Aside from MSC, numerous studies have demonstrated a positive impact of EPC on pulmonary vascular growth and regeneration [3,43]. However, some studies show conflicting results or fail to demonstrate an impact of bone marrow-derived EPC on vascular regeneration in acute lung injury and other conditions [44,45].…”