Healthy versus Inflamed Lung Environments Differentially Effect MSCs
(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.
(Less)
- author
- organization
- publishing date
- 2021-10-01
- 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}}, }