Microvesicles are anuclear fragments of cells released from endosomal compartment or shed from surface membranes. We and other investigators demonstrated that microvesicles released by mesenchymal stem cells were as effective as the cells themselves in inflammatory injuries, such as following endotoxin-induced acute lung injury. However, the therapeutic effects of microvesicles in an infectious model of acute lung injury remain unknown.
We investigated the effects of human mesenchymal stem cell microvesicles on lung inflammation, protein permeability, bacterial clearance and survival following severe bacterial pneumonia.
We tested the effects of microvesicles derived from human mesenchymal stem cells on Escherichia coli pneumonia in mice. We also studied the interactions between microvesicles and human monocytes and human alveolar epithelial type 2 cells.
MEASUREMENTS AND MAIN RESULTS:
Administration of microvesicles derived from human mesenchymal stem cells improved survival in part through keratinocyte growth factor secretion and decreased the influx of inflammatory cells, cytokines, protein, and bacteria in mice injured with bacterial pneumonia. In primary cultures of human monocytes or alveolar type 2 cells, the uptake of microvesicles was mediated by CD44 receptors, which were essential for the therapeutic effects. Microvesicles enhanced monocyte phagocytosis of bacteria, while decreasing inflammatory cytokine secretion, and increased intracellular ATP levels in injured alveolar epithelial type 2 cells. Pre-stimulation of mesenchymal stem cells with a toll-like receptor 3 agonist further enhanced the therapeutic effects of the released microvesicles.
Microvesicles derived from human mesenchymal stem cells were as effective as the parent stem cells in severe bacterial pneumonia.