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Cited by 688Extracellular vesicles in diseaseMesenchymal stem cell researchRespiratory Support and Mechanisms

Human Mesenchymal Stem Cell Microvesicles for Treatment of Escherichia coli Endotoxin-Induced Acute Lung Injury in Mice

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Zhu, Ying-gang, Feng, Xiao-mei, Abbott, Jason, Fang, Xiao-hui, Hao, Qi, Monsel, Antoine, Qu, Jie-ming, Matthay, Michael A. +1 more·2014·Stem Cells
DOI 10.1002/stem.1504PMC PMC3947321
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Abstract

We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia coli endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. coli endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. coli endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus. Stem Cells 2014;32:116–125

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Authors
Zhu, Y.-G., Feng, X.-M., Abbott, J., Fang, X.-H., Hao, Q., Monsel, A., Qu, J.-M., Matthay, M. A., & Lee, J. W.
Affiliations
  • Department of Pulmonary Medicine Huadong Hospital, Fudan University, Shanghai, People's Republic of China
  • Department of Anesthesiology Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
  • University of California, San Francisco (US)
  • Cardiovascular Research Institute University of California San Francisco, San Francisco, California, USA
  • Department of Anesthesiology University of California San Francisco, San Francisco, California, USA
Corresponding author
Lee, Jae W.
ORCID
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2014-01-01
Volume
32
Issue
1
Pages
116-125
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
DOI
10.1002/stem.1504
PMC
PMC3947321
OpenAlex
W1479842253
Cited by
688
References
3
Citations by year
2026: 12 · 2025: 29 · 2024: 42 · 2023: 49 · 2022: 67 · 2021: 96 · 2020: 104 · 2019: 62 · 2018: 50 · 2017: 59 · 2016: 56 · 2015: 44 · 2014: 16 · 2013: 2
FWCI
17.63
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Stem Cells (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • NHLBI (HL-51854, HL-093026, HL-113022)
  • UCSF Hamilton Endowment Funds
  • NCRR
  • NIH (P40RR017447)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
Keywords
acute lung injury, Escherichia coli endotoxin, lipopolysaccharide-induced lung injury, keratinocyte growth factor, bone marrow-derived mesenchymal stem cells, pulmonary edema, alveolitis, neutrophil infiltration, CXCL2, microRNA, siRNA knockdown, stem cell therapy
MeSH terms
Animals, Endotoxins, Escherichia coli, Humans, Lipopolysaccharides, Male, Mice, Inbred C57BL, Microscopy, Electron, Mesenchymal Stem Cell Transplantation, Mice, Cell-Derived Microparticles, Acute Lung Injury, Mesenchymal Stem Cells

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