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Published on: June 17, 2016
The Effects of the Pneumonia Lung Microenvironment on MSC Function
Lanzhi Liu1,2, Juan Fandiño1,3, Sean D McCarthy1,3
1CÚRAM Institute for Medical Devices, University of Galway, H91 W2TY Galway, Ireland.
Background:
Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient's disease state. Here, we explored this interaction, seeking to devise strategies to enhance MSC therapeutic function.
Methods:
Human bone-marrow-derived MSCs were exposed to lung homogenate from healthy and E. coli-induced ARDS rat models. Apoptosis and functional assays of the MSCs were performed.
Results:
The ARDS model showed reduced arterial oxygenation, decreased lung compliance and an inflammatory microenvironment compared to controls. MSCs underwent more apoptosis after stimulation by lung homogenate from controls compared to E. coli, which may explain why MSCs persist longer in ARDS subjects after administration. Changes in expression of cell surface markers and cytokines were associated with lung homogenate from different groups. The anti-microbial effects of MSCs did not change with the stimulation. Moreover, the conditioned media from lung-homogenate-stimulated MSCs inhibited T-cell proliferation.
Conclusions:
These findings suggest that the ARDS microenvironment plays an important role in the MSC's therapeutic mechanism of action, and changes can inform strategies to modulate MSC-based cell therapy for ARDS.
Insights
Mesenchymal stem cells (MSCs) show potential for acute respiratory distress syndrome (ARDS), but clinical success is limited. Understanding the ARDS microenvironment
Area of Science:
- Regenerative Medicine
- Cell Therapy
- Pulmonology
Background:
- Mesenchymal stem cells (MSCs) show promise in preclinical acute respiratory distress syndrome (ARDS) models.
- Clinical trials have not yet translated this promise into therapeutic benefit.
- MSC function is influenced by the patient's disease state, necessitating further investigation.
Purpose of the Study:
- To explore the interaction between MSCs and the ARDS microenvironment.
- To identify strategies for enhancing MSC therapeutic function in ARDS.
- To understand how ARDS affects MSC behavior and efficacy.
Main Methods:
- Human bone-marrow-derived MSCs were exposed to lung homogenate from healthy and E. coli-induced ARDS rat models.
- Apoptosis and functional assays were performed on stimulated MSCs.
- Changes in cell surface markers and cytokine expression were analyzed.
Main Results:
- MSCs exhibited increased apoptosis when stimulated by healthy lung homogenate compared to ARDS homogenate, potentially explaining longer persistence in ARDS patients.
- ARDS lung homogenate altered MSC cell surface marker and cytokine expression.
- Conditioned media from stimulated MSCs inhibited T-cell proliferation, indicating immunomodulatory effects.
Conclusions:
- The ARDS microenvironment significantly influences MSC therapeutic mechanisms.
- Understanding these interactions can inform strategies to optimize MSC-based cell therapy for ARDS.
- Modulating MSCs based on microenvironmental cues may improve treatment outcomes.
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