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Cited by 30Extracellular vesicles in diseaseMesenchymal stem cell researchMicroRNA in disease regulation

Role of miR‐466 in mesenchymal stromal cell derived extracellular vesicles treating inoculation pneumonia caused by multidrug‐resistant Pseudomonas aeruginosa

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Shi, Meng‐meng, Zhu, Ying‐gang, Yan, Jia‐yang, Rouby, Jean‐Jacques, Summah, Hanssa, Monsel, Antoine, Qu, Jie‐ming·2021·Clinical and Translational Medicine
DOI 10.1002/ctm2.287PMC PMC7805403
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Abstract

RATIONALE: The effects of mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC EVs) on multidrug-resistant pseudomonas aeruginosa (MDR-PA)-induced pneumonia remain unclear. MATERIALS AND METHODS: MicroRNA array and RT-PCR were used to select the major microRNA in MSC EVs. Human peripheral blood monocytes were obtained and isolated from qualified patients. The crosstalk between MSCs/MSC EVs and macrophages in vitro was studied. MDR-PA pneumonia models were further established in C57BL/6 mice and MSC EVs or miR-466 overexpressing MSC EVs were intratracheally instilled. RESULTS: MiR-466 was highly expressed in MSC EVs. MSCs and miR-466 promoted macrophage polarization toward Type 2 phenotype through TIRAP-MyD88-NFκB axis. Moreover, cocultured macrophages with miR-466 overexpressing MSCs significantly increased the phagocytosis of macrophages. MSC EVs significantly reduced mortality and decreased influx of BALF neutrophils, proinflammatory factor levels, protein, and bacterial load in murine MDR-PA pneumonia. Administration of miR-466 overexpressing MSC EVs further alleviated the inflammatory severity. CONCLUSIONS: MSC-derived EVs containing high levels of miR-466 may partly participate in host immune responses to MDR-PA. Both MSCs and MSC EVs have therapeutic effects in treating MDR-PA-induced pneumonia.

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  • Mesenchymal stromal cells exposed to Pseudomonas aeruginosa secrete miR-466-rich exosomes, which divert macrophages towards M2 polarization via binding with TIRAP.

    “For instance, mesenchymal stromal cells exposed to Pseudomonas aeruginosa secrete miR-466-rich exosomes, which divert macrophages towards M2 polarization via binding with TIRAP [176].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [176]

    The Results report that adipose-derived MSC extracellular vesicles are rich in miR-466, and the Discussion links miR-466 to M2 macrophage polarization through TIRAP targeting. However, the Methods describe isolating vesicles from cultured MSCs, not MSCs exposed to Pseudomonas aeruginosa; macrophages were exposed to the bacterium. The paper identifies TIRAP mRNA as a target, rather than demonstrating binding to the TIRAP protein. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Administration of exosomes containing miR-466 can reduce mortality in P. aeruginosa pneumonia through immunomodulatory function.

    “administration of exosomes containing miR-466 can reduce mortality in P. aeruginosa pneumonia through their immunomodulatory function [176].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [176]

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  1. [1]Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital‐acquired and ventilator‐associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of America and the American Thoracic Society. Clin Infect Dis. 2016; 63(5): e61‐ e111. 27418577 PMC4981759
  2. [2]Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital‐acquired pneumonia and ventilator‐associated pneumonia: guidelines for the management of hospital‐acquired pneumonia (HAP)/ventilator‐associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J. 2017; 50(3). DOI: 10.1183/13993003.00582-2017 28890434 · DOI · Paper page
  3. [3]Shorr AF. Review of studies of the impact on Gram‐negative bacterial resistance on outcomes in the intensive care unit. Crit Care Med. 2009; 37(4): 1463‐ 1469. 19242341
  4. [4]Luyt CE, Hékimian G, Koulenti D, Chastre J. Microbial cause of ICU‐acquired pneumonia: hospital‐acquired pneumonia versus ventilator‐associated pneumonia. Curr Opin Crit Care. 2018; 24(5): 332‐ 338. 30036192
  5. [5]Xiao M, Wang Y, Yang QW, et al. Antimicrobial susceptibility of pseudomonas aeruginosa in China: a review of two multicentre surveillance programmes, and application of revised CLSI susceptibility breakpoints. Int J Antimicrob Agents. 2012; 40(5): 445‐ 449. 22910455
  6. [6]Zhu YG, Hao Q, Monsel A, Feng XM, Lee JW. Adult stem cells for acute lung injury: remaining questions and concerns. Respirology. 2013; 18(5): 744‐ 756. 23578018 PMC3690944
  7. [7]Monsel A, Zhu YG, Gennai S, Hao Q, Liu J, Lee JW. Cell‐based therapy for acute organ injury: preclinical evidence and ongoing clinical trials using mesenchymal stem cells. Anesthesiology. 2014; 121(5): 1099‐ 1121. 25211170 PMC4206665
  8. [8]Monsel A, Zhu YG, Gudapati V, Lim H, Lee JW. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther. 2016; 16(7): 859‐ 871. 27011289 PMC5280876
  9. [9]Tang XD, Shi L, Monsel A, et al. Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang‐1 mRNA. Stem Cells. 2017; 35(7): 1849‐ 1859. 28376568
  10. [10]Morrison TJ, Jackson MV, Cunningham EK, et al. Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med. 2017; 196(10): 1275‐ 1286. 28598224 PMC5694830
  11. [11]Wilson JG, Liu KD, Zhuo H, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015; 3(1): 24‐ 32. 25529339 PMC4297579
  12. [12]Liu KD, Wilson JG, Zhuo H, et al. Design and implementation of the START (STem cells for ARDS treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate‐severe acute respiratory distress syndrome. Ann Intensive Care. 2014; 4: 22. 25593740 PMC4273700
  13. [13]Kim ES, Chang YS, Choi SJ, et al. Intratracheal transplantation of human umbilical cord blood‐derived mesenchymal stem cells attenuates Escherichia coli‐induced acute lung injury in mice. Respir Res. 2011; 12: 108. 21843339 PMC3166924
  14. [14]Lee JW, Krasnodembskaya A, McKenna DH, Song Y, Abbott J, Matthay MA. Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria. Am J Respir Crit Care Med. 2013; 187(7): 751‐ 760. 23292883 PMC3678109
  15. [15]Mao YX, Xu JF, Seeley EJ, et al. Adipose tissue‐derived mesenchymal stem cells attenuate pulmonary infection caused by pseudomonas aeruginosa via inhibiting overproduction of prostaglandin E2. Stem Cells. 2015; 33(7): 2331‐ 2342. 25788456
  16. [16]Devaney J, Horie S, Masterson C, et al. Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat. Thorax. 2015; 70(7): 625‐ 635. 25986435
  17. [17]Sung DK, Chang YS, Sung SI, Yoo HS, Ahn SY, Park WS. Antibacterial effect of mesenchymal stem cells against Escherichia coli is mediated by secretion of beta‐ defensin‐ 2 via toll‐ like receptor 4 signalling. Cell Microbiol. 2016; 18(3): 424‐ 436. 26350435 PMC5057339
  18. [18]Curley GF, Jerkic M, Dixon S, et al. Xeno‐free human umbilical cord mesenchymal stromal cells reduce lung injury severity and bacterial burden in rodent Escherichia coli‐induced acute respiratory distress syndrome. Crit Care Med. 2017; 45(2): e202‐ e212. 27861182
  19. [19]Gupta N, Krasnodembskaya A, Kapetanaki M, et al. Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax. 2012; 67(6): 533‐ 539. 22250097 PMC3358432
  20. [20]Monsel A, Zhu YG, Gennai S, et al. therapeutic effects of human mesenchymal stem cell‐derived microvesicles in severe pneumonia in mice. Am J Respir Crit Care Med. 2015; 192(3): 324‐ 336. 26067592 PMC4584251
  21. [21]Park J, Kim S, Lim H, et al. Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia. Thorax. 2019; 74(1): 43‐ 50. 30076187 PMC6295323
  22. [22]Zhu YG, Feng XM, Abbott J, et al. Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin‐induced acute lung injury in mice. Stem Cells. 2014; 32(1): 116‐ 125. 23939814 PMC3947321
  23. [23]Ambros V. The functions of animal microRNAs. Nature. 2004; 431(7006): 350‐ 355. 15372042
  24. [24]Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2): 281‐ 297. 14744438
  25. [25]Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008; 319(5867): 1244‐ 1247. 18309083
  26. [26]Lu Q, Eggimann P, Luyt CE, et al. Pseudomonas aeruginosa serotypes in nosocomial pneumonia: prevalence and clinical outcomes. Critical Care. 2014; 18: R17. 24428878 PMC4057348
  27. [27]Raymond CK, Sims EH, Kas A, et al. Genetic variation at the O‐antigen biosynthetic locus in Pseudomonas aeruginosa. J Bacteriol. 2002; 184(13): 3614‐ 3622. 12057956 PMC135118
  28. [28]Mizgerd JP, Skerrett SJ. Animal models of human pneumonia. Am J Physiol Lung Cell Mol Physiol. 2008; 294(3): L387‐ L398. 18162603
  29. [29]Matute‐Bello G, Downey G, Moore BB, et al. Acute lung injury in animals study group. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011; 44(5): 725‐ 738. 21531958 PMC7328339
  30. [30]Rittirsch D, Hoesel LM, Ward PA. The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol. 2007; 81(1): 137‐ 143. 17020929
  31. [31]Calabrese JM, Seila AC, Yeo GW, Sharp PA. RNA sequence analysis defines Dicer's role in mouse embryonic stem cells. Proc Natl Acad Sci USA. 2007; 104(46): 18097‐ 18102. 17989215 PMC2084302
  32. [32]Ma F, Liu X, Li D, et al. MicroRNA‐466l upregulates IL‐10 expression in TLR‐triggered macrophages by antagonizing RNA‐binding protein tristetraprolin‐mediated IL‐10 mRNA degradation. J Immunol. 2010; 184(11): 6053‐ 6059. 20410487
  33. [33]Li Y, Fan X, He X, et al. MicroRNA‐466l inhibits antiviral innate immune response by targeting interferon‐alpha. Cell Mol Immunol. 2012; 9(6): 497‐ 502. 23042536 PMC4002216
  34. [34]Mukherjee B, Paul J, Mukherjee S, et al. Antimony‐resistant leishmania donovani exploits miR‐466i to deactivate host MyD88 for regulating IL‐10/IL‐12 levels during early hours of infection. J Immunol. 2015; 195(6): 2731‐ 2742. 26283478
  35. [35]Locati M, Mantovani A, Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol. 2013; 120: 163‐ 184. 24070384
  36. [36]Németh K, Leelahavanichkul A, Yuen PS, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)‐dependent reprogramming of host macrophages to increase their interleukin‐10 production. Nat Med. 2009; 15(1): 42‐ 49. 19098906 PMC2706487
  37. [37]Krasnodembskaya A, Samarani G, Song Y, et al. Human mesenchymal stem cells reduce mortality and bacteremia in gram‐negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol. 2012; 302(10): L1003‐ L1013. 22427530 PMC3362255
  38. [38]Ionescu L, Byrne RN, van Haaften T, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol. 2012; 303(11): L967‐ 77. 23023971 PMC3532523
  39. [39]Lo Sicco C, Reverberi D, Balbi C, et al. Mesenchymal stem cell‐derived extracellular vesicles as mediators of anti‐inflammatory effects: endorsement of macrophage polarization. Stem Cells Transl Med. 2017; 6(3): 1018‐ 1028. 28186708 PMC5442783
  40. [40]Horng T, Barton GM, Medzhitov R. TIRAP: an adapter molecule in the toll signaling pathway. Nat Immunol. 2001; 2(9): 835‐ 841. 11526399
  41. [41]Kagan JC, Medzhitov R. Phosphoinositide‐mediated adaptor recruitment controls toll‐like receptor signaling. Cell. 2006; 125(5): 943‐ 955. 16751103
  42. [42]Fitzgerald KA, Palsson‐McDermott EM, Bowie AG, et al. Mal (MyD88‐adapter‐like) is required for toll‐like receptor‐4 signal transduction. Nature. 2001; 413(6851): 78‐ 83. 11544529
  43. [43]Yamamoto M, Sato S, Hemmi H, et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature. 2002; 420(6913): 324‐ 329. 12447441
  44. [44]Horng T, Barton GM, Flavell RA, Medzhitov R. The adaptor molecule TIRAP provides signalling specificity for toll‐like receptors. Nature. 2002; 420(6913): 329‐ 333. 12447442
  45. [45]Gilmore TD. Introduction to NF‐kappaB: players, pathways, perspectives. Oncogene. 2006; 25(51): 6680‐ 6684. 17072321
  46. [46]Napetschnig J, Wu H. Molecular basis of NF‐κB signaling. Annu Rev Biophys. 2013; 42: 443‐ 468. 23495970 PMC3678348

Cited by

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Authors
Shi, M., Zhu, Y., Yan, J., Rouby, J., Summah, H., Monsel, A., & Qu, J.
Affiliations
  • Department of Respiratory and Critical Care Medicine, Ruijin Hospital, School of Medicine Shanghai Jiao Tong University Shanghai China
  • Department of Pulmonary and Critical Care Medicine, Hua‐dong Hospital Fudan University Shanghai China
  • Sorbonne Université (FR)
  • Shanghai Jiao Tong University (CN)
  • Inserm (FR)
ORCID
Venue
Clinical and Translational Medicine
Publisher
Wiley
Published
2021-01
Volume
11
Issue
1
Pages
e287-e287
ISSN
2001-1326 (ISSN-L)
DOI
10.1002/ctm2.287
PMC
PMC7805403
OpenAlex
W3118700303
Cited by
30
References
1
Citations by year
2026: 6 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 5
FWCI
1.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical and Translational Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
National Natural Science Foundation of China (81570066, 81630001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
mesenchymal stem cells, extracellular vesicles, multidrug-resistant Pseudomonas aeruginosa, Pseudomonas aeruginosa pneumonia, macrophage polarization, macrophage phagocytosis, neutrophil infiltration, host immune response, anti-inflammatory therapy
MeSH terms
Extracellular Vesicles, Animals, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Pneumonia, Pseudomonas aeruginosa, Drug Resistance, Multiple, MicroRNAs, Mice, Mesenchymal Stem Cells

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