The Effects of the Pneumonia Lung Microenvironment on MSC Function

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 18; p. 1581
• Main Authors: Liu, Lanzhi, Fandiño, Juan, McCarthy, Sean D., Masterson, Claire H., Sallent, Ignacio, Du, Shanshan, Warren, Abigail, Laffey, John G., O’Toole, Daniel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.09.2024; MDPI
• Subjects: Acute respiratory distress syndrome; Animal models; Animals; Apoptosis; Bacterial pneumonia; Cell culture; Cell Proliferation; Cell surface; Cell therapy; Cellular Microenvironment; Clinical trials; Cytokines; Cytokines - metabolism; Disease Models, Animal; E coli; Escherichia coli; Flow cytometry; Growth factors; Health aspects; Humans; Inflammation; Lung - pathology; lung microenvironment; Lungs; Lymphocytes T; Male; Medical research; mesenchymal stem cell (MSC); Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Pneumonia; Pneumonia - metabolism; Pneumonia - pathology; Pneumonia - therapy; Proteins; R&D; Rats; Rats, Sprague-Dawley; Research & development; Research ethics; Respiratory distress syndrome; Respiratory Distress Syndrome - metabolism; Respiratory Distress Syndrome - pathology; Respiratory Distress Syndrome - therapy; Surface markers; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; United Kingdom; Ireland; United Kingdom > UK; United States > US; inflammation; mesenchymal stem cell (MSC); lung microenvironment
• DOI: 10.3390/cells13181581
• ISSN: 2073-4409

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.