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Healthy versus Inflamed Lung Environments Differentially Effect MSCs

Enes, Sara Rolandsson LU orcid ; Hampton, Thomas H. ; Barua, Jayita ; McKenna, David H. ; Dos Santos, Claudia C. ; Amiel, Eyal ; Ashare, Alix ; Liu, Kathleen D. ; Krasnodembskaya, Anna D. and English, Karen , et al. (2021) In European Respiratory Journal 58(4).
Abstract

Background: Despite increased interest in MSC-based cell therapies for the acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and understanding of the potential in vivo mechanisms of MSC actions in ARDS remain limited. ARDS is driven by an acute severe innate immune dysregulation, often characterized by inflammation, coagulation, and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined. Aim: To comparatively assess how the inflammatory environment present in ARDS lungs vs. the lung environment present in healthy volunteers alters MSC behaviors. Methods: Clinical grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar... (More)

Background: Despite increased interest in MSC-based cell therapies for the acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and understanding of the potential in vivo mechanisms of MSC actions in ARDS remain limited. ARDS is driven by an acute severe innate immune dysregulation, often characterized by inflammation, coagulation, and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined. Aim: To comparatively assess how the inflammatory environment present in ARDS lungs vs. the lung environment present in healthy volunteers alters MSC behaviors. Methods: Clinical grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties including viability, levels of expression of inflammatory cytokines, gene expression, cell surface HLA expression, and activation of coagulation and complement pathways. Results: Pro-inflammatory, pro-coagulant, and major histocompatibility complex (self recognition) related gene and protein expression was markedly up-regulated in hMSCs exposed ex vivo to BALF obtained from healthy volunteers. In contrast, these changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples. Conclusion: These data provide new insights into how hMSCs behave in healthy vs. inflamed lung environments strongly suggesting that the inflamed environment in ARDS induces hMSC responses potentially benefical for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute Respiratory Distress Syndrome, Bronchoalveolar Lavage Fluid, Cell Therapy, Inflammation, Mesenchymal Stromal Cells
in
European Respiratory Journal
volume
58
issue
4
publisher
European Respiratory Society
external identifiers
  • pmid:33795318
  • scopus:85118238000
  • scopus:85105600388
ISSN
0903-1936
DOI
10.1183/13993003.04149-2020
language
English
LU publication?
yes
id
8c8d22dc-4791-451a-a3f0-6a2c1caaa277
date added to LUP
2022-03-08 11:24:37
date last changed
2024-04-14 02:26:55
@article{8c8d22dc-4791-451a-a3f0-6a2c1caaa277,
  abstract     = {{<p>Background: Despite increased interest in MSC-based cell therapies for the acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and understanding of the potential in vivo mechanisms of MSC actions in ARDS remain limited. ARDS is driven by an acute severe innate immune dysregulation, often characterized by inflammation, coagulation, and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined. Aim: To comparatively assess how the inflammatory environment present in ARDS lungs vs. the lung environment present in healthy volunteers alters MSC behaviors. Methods: Clinical grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties including viability, levels of expression of inflammatory cytokines, gene expression, cell surface HLA expression, and activation of coagulation and complement pathways. Results: Pro-inflammatory, pro-coagulant, and major histocompatibility complex (self recognition) related gene and protein expression was markedly up-regulated in hMSCs exposed ex vivo to BALF obtained from healthy volunteers. In contrast, these changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples. Conclusion: These data provide new insights into how hMSCs behave in healthy vs. inflamed lung environments strongly suggesting that the inflamed environment in ARDS induces hMSC responses potentially benefical for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.</p>}},
  author       = {{Enes, Sara Rolandsson and Hampton, Thomas H. and Barua, Jayita and McKenna, David H. and Dos Santos, Claudia C. and Amiel, Eyal and Ashare, Alix and Liu, Kathleen D. and Krasnodembskaya, Anna D. and English, Karen and Stanton, Bruce A. and Rocco, Patricia R.M. and Matthay, Michael A. and Weiss, Daniel J.}},
  issn         = {{0903-1936}},
  keywords     = {{Acute Respiratory Distress Syndrome; Bronchoalveolar Lavage Fluid; Cell Therapy; Inflammation; Mesenchymal Stromal Cells}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{4}},
  publisher    = {{European Respiratory Society}},
  series       = {{European Respiratory Journal}},
  title        = {{Healthy versus Inflamed Lung Environments Differentially Effect MSCs}},
  url          = {{http://dx.doi.org/10.1183/13993003.04149-2020}},
  doi          = {{10.1183/13993003.04149-2020}},
  volume       = {{58}},
  year         = {{2021}},
}