Document Detail

Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria.
MedLine Citation:
PMID:  23292883     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Mesenchymal stem cells secrete paracrine factors that can regulate lung permeability and decrease inflammation, making it a potentially attractive therapy for acute lung injury. However, concerns exist whether mesenchymal stem cells' immunomodulatory properties may have detrimental effects if targeted toward infectious causes of lung injury.
OBJECTIVES: Therefore, we tested the effect of mesenchymal stem cells on lung fluid balance, acute inflammation, and bacterial clearance.
METHODS: We developed an Escherichia coli pneumonia model in our ex vivo perfused human lung to test the therapeutic effects of mesenchymal stem cells on bacterial-induced acute lung injury.
MEASUREMENTS AND MAIN RESULTS: Clinical-grade human mesenchymal stem cells restored alveolar fluid clearance to a normal level, decreased inflammation, and were associated with increased bacterial killing and reduced bacteremia, in part through increased alveolar macrophage phagocytosis and secretion of antimicrobial factors. Keratinocyte growth factor, a soluble factor secreted by mesenchymal stem cells, duplicated most of the antimicrobial effects. In subsequent in vitro studies, we discovered that human monocytes expressed the keratinocyte growth factor receptor, and that keratinocyte growth factor decreased apoptosis of human monocytes through AKT phosphorylation, an effect that increased bacterial clearance. Inhibition of keratinocyte growth factor by a neutralizing antibody reduced the antimicrobial effects of mesenchymal stem cells in the ex vivo perfused human lung and monocytes grown in vitro injured with E. coli bacteria.
CONCLUSIONS: In E. coli-injured human lungs, mesenchymal stem cells restored alveolar fluid clearance, reduced inflammation, and exerted antimicrobial activity, in part through keratinocyte growth factor secretion.
Jae W Lee; Anna Krasnodembskaya; David H McKenna; Yuanlin Song; Jason Abbott; Michael A Matthay
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  187     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-05-21     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  751-60     Citation Subset:  AIM; IM    
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MeSH Terms
Acute Lung Injury / etiology*,  microbiology
Analysis of Variance
Cells, Cultured
Escherichia coli Infections / complications*
Fibroblast Growth Factor 7 / secretion*
Inflammation / therapy
Macrophages, Alveolar / microbiology
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stromal Cells / secretion*
Phagocytosis / physiology
Pneumonia, Bacterial / complications*
Pulmonary Alveoli / metabolism
Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
Grant Support
Reg. No./Substance:
126469-10-1/Fibroblast Growth Factor 7; EC, Fibroblast Growth Factor, Type 2
Comment In:
Am J Respir Crit Care Med. 2013 Apr 1;187(7):674-5   [PMID:  23540875 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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