Human Placental Mesenchymal Stem Cells and Derived Extracellular Vesicles Ameliorate Lung Injury in Acute Respiratory Distress Syndrome Murine Model

Author:

Valiukevičius Paulius1ORCID,Mačiulaitis Justinas23,Pangonytė Dalia3,Siratavičiūtė Vitalija3,Kluszczyńska Katarzyna4ORCID,Kuzaitytė Ugnė1,Insodaitė Rūta2ORCID,Čiapienė Ieva5ORCID,Grigalevičiūtė Ramunė6,Zigmantaitė Vilma6,Vitkauskienė Astra7,Mačiulaitis Romaldas2

Affiliation:

1. Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

2. Institute of Physiology and Pharmacology, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

3. Laboratory of Cardiac Pathology, Institute of Cardiology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

4. Department of Molecular Biology of Cancer, Medical University of Lodz, 90-419 Lodz, Poland

5. Institute of Cardiology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

6. Biological Research Center, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

7. Department of Laboratory Medicine, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

Abstract

This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like lung injury in mice using intranasal LPS instillation and evaluated histological changes, neutrophil accumulation via immunohistochemistry, bronchoalveolar lavage fluid cell count, total protein, and cytokine concentration, as well as lung gene expression changes at three time points: 24, 72, and 168 h. We found that both P-MSCs and EV treatments reduced the histological evidence of lung injury, decreased neutrophil infiltration, and improved alveolar barrier integrity. Analyses of cytokines and gene expression revealed that both treatments accelerated inflammation resolution in lung tissue. Biodistribution studies indicated negligible cell engraftment, suggesting that intraperitoneal P-MSC therapy functions mostly through soluble factors. Overall, both P-MSC and EV therapy ameliorated LPS-induced lung injury. Notably, at the tested dose, EV therapy was more effective than P-MSCs in reducing most aspects of lung injury.

Funder

European Regional Development Fund

Research Council of Lithuania

European Union

Publisher

MDPI AG

Subject

General Medicine

Reference55 articles.

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2. ARDS Definition Task Force, Ranieri, V.M., Rubenfeld, G.D., Thompson, B.T., Ferguson, N.D., Caldwell, E., Fan, E., Camporota, L., and Slutsky, A.S. (2012). Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA, 307, 2526–2533.

3. Acute Respiratory Distress Syndrome: Causes, Pathophysiology, and Phenotypes;Bos;Lancet,2022

4. Management of ARDS—What Works and What Does Not;Banavasi;Am. J. Med. Sci.,2021

5. Incidence of ARDS and Outcomes in Hospitalized Patients with COVID-19: A Global Literature Survey;Tzotzos;Crit. Care,2020

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