Distinct effects of intravenous bone marrow-derived mesenchymal stem cell therapy on ischemic and non-ischemic lungs after ischemiareperfusion injury

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Radicetti-Silva, Julia ; Oliveira, Milena ; Baldavira, Camila Machado ; Braga, Cassia Lisboa ; Santos, Renata Trabach ; Felix, Nathane Santanna ; Silva, Adriana Lopes ; Capelozzi, Vera Luiza ; Cruz, Fernanda Ferreira ; Rocco, Patricia Rieken Macedo ; Silva, Pedro Leme

• Document type: Journal article
• Source: CYTOTHERAPY; v. 26, n. 12, p. 9-pg., 2024-11-12.

Abstract

Background: The preclinical efficacy of mesenchymal stem cell (MSC) therapy after intravenous infusion has been promising, but clinical studies have yielded only modest results. Although most preclinical studies have focused solely on the ischemic lung, it is crucial to evaluate both lungs after ischemia-reperfusion injury, considering the various mechanisms involved. This study aimed to bridge this gap by assessing the acute effects of bone marrow MSC(BM) infusion before ischemic insult and evaluating both ischemic and non-ischemic lungs after reperfusion. Methods: Eighteen male Wistar rats (403 23 g) were anesthetized and mechanically ventilated using a protective strategy. After baseline data collection, the animals were randomized to 3 groups (n = 6/group): (1) SHAM; (2) ischemia-reperfusion (IR), and (3) intravenous MSC(BM) infusion followed by IR. Ischemia was induced by complete clamping of the left hilum, followed by 1 h of reperfusion after clamp removal. At the end of the experiment, the right and left lungs (non-ischemic and ischemic, respectively) were collected for immunohistochemistry and molecular biology analysis. Results: MSC(BM)s reduced endothelial cell damage and apoptosis markers and improved markers associated with endothelial cell integrity in both lungs. In addition, gene expression of catalase and nuclear factor erythroid 2-related factor 2 increased after MSC(BM) therapy. In the ischemic lung, MSC(BM) therapy mitigated endothelial cell damage and apoptosis and increased gene expression associated with endothelial cell integrity. Conversely, in the non-ischemic lung, apoptosis gene expression increased in the IR group but not after MSC(BM) therapy. Conclusion: This study demonstrates distinct effects of MSC(BM) therapy on ischemic and non-ischemic lungs after ischemia-reperfusion injury. The findings underscore the importance of evaluating both lung types in ischemia-reperfusion studies, offering insights into the therapeutic potential of MSC(BM) therapy in the context of lung injury. (c) 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. (AU)

• FAPESP's process: 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets
• Grantee: Vera Luiza Capelozzi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 23/02755-0 - Evaluation of epithelial-mesenchymal transition protein expression as a new perspective in biomarkers for determining prognosis, response and resistance to targeted therapy in non-small cell lung carcinomas
• Grantee: Camila Machado Baldavira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral