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Updated: Jul 30, 2025
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Extracellular Vesicles from Different Sources of Mesenchymal Stromal Cells Have Distinct Effects on Lung and Distal
Natália G Blanco1,2, Natália M Machado1,2, Ligia L Castro1,2
1Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
Abstract:
The effects of the administration of mesenchymal stromal cells (MSC) may vary according to the source. We hypothesized that MSC-derived extracellular vesicles (EVs) obtained from bone marrow (BM), adipose (AD), or lung (L) tissues may also lead to different effects in sepsis. We profiled the proteome from EVs as a first step toward understanding their mechanisms of action. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (SEPSIS) and SHAM (control) animals only underwent laparotomy. Twenty-four hours after surgery, animals in the SEPSIS group were randomized to receive saline or 3 × 106 MSC-derived EVs from BM, AD, or L. The diffuse alveolar damage was decreased with EVs from all three sources. In kidneys, BM-, AD-, and L-EVs reduced edema and expression of interleukin-18. Kidney injury molecule-1 expression decreased only in BM- and L-EVs groups. In the liver, only BM-EVs reduced congestion and cell infiltration. The size and number of EVs from different sources were not different, but the proteome of the EVs differed. BM-EVs were enriched for anti-inflammatory proteins compared with AD-EVs and L-EVs. In conclusion, BM-EVs were associated with less organ damage compared with the other sources of EVs, which may be related to differences detected in their proteome.
Insights
Mesenchymal stromal cell-derived extracellular vesicles (EVs) from different tissues show varied effects in sepsis. Bone marrow EVs demonstrated superior protective effects against organ damage, linked to their unique protein content.
Area of Science:
- Regenerative Medicine
- Immunology
- Cell Biology
Background:
- Mesenchymal stromal cells (MSCs) are investigated for therapeutic potential.
- MSC-derived extracellular vesicles (EVs) are emerging as cell-free therapeutic agents.
- The source of MSCs may influence the therapeutic efficacy of their EVs.
Purpose of the Study:
- To investigate the effects of EVs derived from bone marrow (BM), adipose (AD), and lung (L) tissues in a mouse model of sepsis.
- To compare the therapeutic potential of BM-EVs, AD-EVs, and L-EVs in mitigating sepsis-induced organ damage.
- To analyze the proteomic profiles of EVs from different sources to understand their mechanisms of action.
Main Methods:
- Polymicrobial sepsis induced in mice via cecal ligation and puncture (CLP).
- Administration of MSC-derived EVs (BM, AD, or L) or saline 24 hours post-CLP.
- Assessment of organ damage (lungs, kidneys, liver) and molecular markers (interleukin-18, Kidney injury molecule-1).
- Proteomic profiling of EVs from different tissue sources.
Main Results:
- EVs from all three sources (BM, AD, L) reduced diffuse alveolar damage in lungs.
- BM-, AD-, and L-EVs decreased kidney edema and interleukin-18 expression.
- BM- and L-EVs reduced Kidney injury molecule-1 expression; only BM-EVs reduced liver congestion and infiltration.
- Proteomic analysis revealed differences in EV composition, with BM-EVs enriched in anti-inflammatory proteins.
Conclusions:
- MSC-derived EVs exhibit source-dependent therapeutic effects in sepsis.
- Bone marrow-derived EVs demonstrated the most significant protection against multi-organ damage in sepsis.
- Differences in EV proteomes, particularly the enrichment of anti-inflammatory proteins in BM-EVs, likely underlie their superior efficacy.
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