Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant Klebsiella pneumoniae
Abstract
:1. Introduction
2. Results
2.1. Pre-Activation Enhances the Functionality of UC-MSCs In Vitro
2.2. Pre-Activation of MSCs Attenautes Physiological Dysfunction in Established Klebsiella pneumosepsis
2.3. Naïve and Cytomix-Exposed MSCs Attenuate K. pneumonia-Induced Histologic Injury
2.4. MSCs Differentually Attenuate the Pulmonary Cytokine Response to K. penumonia Infection
2.5. BAL White Cell Subsets Indicate a Resolution of Pneumonia Following MSC Administration
2.6. BAL Macrophages/Monocytes Show Enhanced Cell Function Following MSC Administration
2.7. Systemic Leukocyte and Lymphocyte Number and Function Are Altered by the Administration of Naïve and Cytomix-Pre-Activated MSCs
3. Discussion
4. Materials and Methods
4.1. Human Umbilical Cord-Derived MSCs
4.2. In Vitro Assay Panels to Ascertain MSC Functionality
4.2.1. Wound-Healing Assay
4.2.2. Nuclear Factor κB Activation Assay
4.2.3. Cell Metabolic Activity
4.2.4. Inflammatory Cytokine Production
4.2.5. Bacterial-Killing Assay
4.3. Preclinical Experimental Series
4.3.1. Established Pneumonia
4.3.2. Experimental Design
4.3.3. Premortem Assessment
4.4. Postmortem Assessment
4.4.1. Bacterial Load
4.4.2. Inflammatory Cytokine Profile
4.4.3. Histological Analyses
4.4.4. Flow Cytometry Analysis of PBMCs
4.4.5. Flow Cytometry Analysis of Neutrophils
4.4.6. BAL Macro/Monocyte Phagocytosis and Superoxide Anion Production
4.4.7. BAL Macro/Monocyte Quantification
4.5. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Byrnes, D.; Masterson, C.H.; Brady, J.; Alagesan, S.; Gonzalez, H.E.; McCarthy, S.D.; Fandiño, J.; O’Toole, D.P.; Laffey, J.G. Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant Klebsiella pneumoniae. Pharmaceuticals 2023, 16, 149. https://doi.org/10.3390/ph16020149
Byrnes D, Masterson CH, Brady J, Alagesan S, Gonzalez HE, McCarthy SD, Fandiño J, O’Toole DP, Laffey JG. Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant Klebsiella pneumoniae. Pharmaceuticals. 2023; 16(2):149. https://doi.org/10.3390/ph16020149
Chicago/Turabian StyleByrnes, Declan, Claire H. Masterson, Jack Brady, Senthilkumar Alagesan, Hector E. Gonzalez, Sean D. McCarthy, Juan Fandiño, Daniel P. O’Toole, and John G. Laffey. 2023. "Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant Klebsiella pneumoniae" Pharmaceuticals 16, no. 2: 149. https://doi.org/10.3390/ph16020149