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Nebulized mesenchymal stem cells derived conditioned media retains the capacity to mitigate lung injury in vivo

H Gonzalez Esteban, S Mccarthy, C Masterson, D Byrnes, R Macloughlin, J Laffey, D O'Toole
European Respiratory Journal 2022 60: 4474; DOI: 10.1183/13993003.congress-2022.4474
H Gonzalez Esteban
1National University of Ireland, Galway, Galway, Ireland
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S Mccarthy
1National University of Ireland, Galway, Galway, Ireland
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C Masterson
1National University of Ireland, Galway, Galway, Ireland
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D Byrnes
1National University of Ireland, Galway, Galway, Ireland
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R Macloughlin
2Aerogen Ltd., Galway, Ireland
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J Laffey
1National University of Ireland, Galway, Galway, Ireland
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D O'Toole
1National University of Ireland, Galway, Galway, Ireland
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Abstract

Rationale: Mesenchymal stem cells (MSC) have shown immense therapeutic promise in acute respiratory distress syndrome (ARDS). Recent studies have shown that the MSC secretome can recapitulate many of the beneficial effects of the MSC itself. We aimed to prove the therapeutic capacity of MSC conditioned media (CM) in ameliorating lung injury in vivo when delivered directly by nebulization.

Methods: MSC-CM was delivered intratracheally (IT) or nebulized into the lungs using a vibrating mesh nebulizer to rats who had undergone lung installation of bacteria, with administration delayed by one hour. 48 hours later, animals were assessed for a range of lung physiological, inflammatory and infection parameters.

Results: Nebulized MSC-CM reduced the alveolar arterial O2 gradient and reduce lung oedema. In a cytokine multiplex assay, proinflammatory cytokines such as IL-1b and IL-6 were ameliorated in bronchoalveolar lavage (BAL).

Conclusion: MSC-CM is a potential therapeutic for pneumonia ARDS, and administration is compatible with vibrating mesh nebulization.

Figure. MSC-CM nebulized one hour after bacterial pneumonia induction reduced BAL IL-6 concentrations compared with vehicle and was not statistically different from the instilled group. († = p<0.05 wrt Sham; * = p<0.05 wrt Vehicle. ns = no significance difference between delivery routes. (Sham: n=4. Vehicle, MSC-CM IT, MSC-CM NEB: n=8)

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  • ARDS (Acute Respiratory Distress Syndrome)
  • Pneumonia
  • Inflammation

Footnotes

Cite this article as Eur Respir J 2022; 60: Suppl. 66, 4474.

This article was presented at the 2022 ERS International Congress, in session “-”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2022
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Nebulized mesenchymal stem cells derived conditioned media retains the capacity to mitigate lung injury in vivo
H Gonzalez Esteban, S Mccarthy, C Masterson, D Byrnes, R Macloughlin, J Laffey, D O'Toole
European Respiratory Journal Sep 2022, 60 (suppl 66) 4474; DOI: 10.1183/13993003.congress-2022.4474

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Nebulized mesenchymal stem cells derived conditioned media retains the capacity to mitigate lung injury in vivo
H Gonzalez Esteban, S Mccarthy, C Masterson, D Byrnes, R Macloughlin, J Laffey, D O'Toole
European Respiratory Journal Sep 2022, 60 (suppl 66) 4474; DOI: 10.1183/13993003.congress-2022.4474
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