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Published on: December 12, 2025
Therapeutic Effects of Human Mesenchymal Stem Cell-derived Microvesicles in Severe Pneumonia in Mice
Antoine Monsel1,2,3, Ying-gang Zhu3, Stephane Gennai3
11 Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, University Pierre and Maris Curie (UPMC) Univ Paris 06, Paris, France.
Rationale:
Microvesicles (MVs) are anuclear fragments of cells released from the endosomal compartment or shed from surface membranes. We and other investigators demonstrated that MVs released by mesenchymal stem cells (MSCs) were as effective as the cells themselves in inflammatory injuries, such as after endotoxin-induced acute lung injury. However, the therapeutic effects of MVs in an infectious model of acute lung injury remain unknown.
Objectives:
We investigated the effects of human MSC MVs on lung inflammation, protein permeability, bacterial clearance, and survival after severe bacterial pneumonia.
Methods:
We tested the effects of MVs derived from human MSCs on Escherichia coli pneumonia in mice. We also studied the interactions between MVs and human monocytes and human alveolar epithelial type 2 cells.
Measurements And Main Results:
Administration of MVs derived from human MSCs 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 MVs was mediated by CD44 receptors, which were essential for the therapeutic effects. MVs enhanced monocyte phagocytosis of bacteria while decreasing inflammatory cytokine secretion and increased intracellular ATP levels in injured alveolar epithelial type 2 cells. Prestimulation of MSCs with a toll-like receptor 3 agonist further enhanced the therapeutic effects of the released MVs.
Conclusions:
MVs derived from human MSCs were as effective as the parent stem cells in severe bacterial pneumonia.
Insights
Mesenchymal stem cell microvesicles (MSCs MVs) improved survival and reduced lung inflammation in bacterial pneumonia. These MVs enhanced bacterial clearance and immune cell function, offering therapeutic potential.
Area of Science:
- Cell Biology
- Immunology
- Regenerative Medicine
Background:
- Microvesicles (MVs) are cell fragments with therapeutic potential.
- MVs from mesenchymal stem cells (MSCs) show efficacy in inflammatory injuries.
- Therapeutic effects of MSC MVs in bacterial pneumonia are unexplored.
Purpose of the Study:
- To investigate the therapeutic effects of human MSC MVs in a bacterial pneumonia model.
- To assess the impact of MSC MVs on lung inflammation, protein permeability, bacterial clearance, and survival.
- To explore the mechanisms of MSC MV interaction with immune and alveolar cells.
Main Methods:
- Administered MVs from human MSCs to mice with Escherichia coli pneumonia.
- Studied MV interactions with human monocytes and alveolar epithelial type 2 cells.
- Investigated the role of CD44 receptors in MV uptake and therapeutic effects.
Main Results:
- MSC MVs improved survival, reduced inflammatory cell influx, and decreased bacterial load.
- MV-mediated therapeutic effects involved keratinocyte growth factor secretion.
- Uptake of MVs by monocytes and alveolar cells was CD44-dependent.
- MVs enhanced monocyte phagocytosis and alveolar cell ATP levels while reducing cytokine secretion.
- Pre-stimulation of MSCs enhanced MV therapeutic efficacy.
Conclusions:
- Human MSC MVs demonstrated therapeutic efficacy comparable to parent MSCs in severe bacterial pneumonia.
- MSC MVs offer a promising cell-free therapeutic strategy for bacterial lung infections.
