Background: Cigarette smoke (CS)-induced lung inflammation and Chronic Obstructive Pulmonary disease (COPD) involves mitochondrial dysfunction. Mesenchymal stem cells (MSC) and MSC-derived exosomes (EXO) are reported to show therapeutic effects in many animal models of inflammation and injury. In the present study, we determined the role of MSC and EXO intervention in CS-induced lung inflammation with a focus on mitochondrial dysfunction.
Methods: EXO were characterized using Western blot for exosomal markers, tunable resistive pulse sensing by qNano and transmission electron microscopy (TEM). Mitochondrial reporter mice (mt-Keima and mito-QC) were exposed to air or CS for 10 days. mt-Keima mice were treated with intraperitoneal injections of MSC or EXO or MSC and EXO (MSC + EXO) for 10 days. Total cell counts, differential cell counts were performed using automated cell counter and flow cytometry respectively. Further, the levels of pro-inflammatory mediators in bronchoalveolar lavage (BAL) fluid were measured using ELISA. Western blot analysis, quantitative PCR, confocal microscopy were used in the current study to determine the effects in the lungs of CS exposed mice. Seahorse flux analyzer was used to measure the oxidative-phosphorylation (OXPHOS) in the BEAS2B cells and BEAS2B - mMSC co-culture experiments.
Results: CS exposure increased the inflammatory cellular infiltrations in the lungs of the mt-Keima mice. MSC + EXO treatment showed protection compared to individual treatments (MSC or EXO alone). There were no changes in the mitophagy proteins like PINK1 and Parkin, which was also found using the mito-QC mice. CS exposure led to significant increase in the mitochondrial fission protein DRP1 and other DAMPs pathway mediators like S100A4 and S100A8, HMGB1, RAGE and AGE. MSC + EXO treatment increased the gene expression of (fusion genes) mfn1, mfn2 and opa1. Additionally, the rhot1 gene expression was increased in MSC + EXO treatment group compared to Air- and CS exposed groups. BEAS2B-mMSC co-cultures showed protective response against the CSE-altered mitochondrial respiration parameters, confirming the beneficial effect of MSC towards human bronchial lung epithelial cells.
Conclusion: CS affects some of early mitochondrial genes involved in the fission/fusion process, enhancing the damage response along with altered cytokine levels. MSC + EXO combination treatment showed their protective effects. MSC + EXO combination treatment may act against these early events caused by CS exposure owing to its anti-inflammatory and other mitochondrial transfer mechanisms.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894395 | PMC |
http://dx.doi.org/10.1016/j.taap.2019.114788 | DOI Listing |
Allergol Immunopathol (Madr)
January 2025
Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zheiiang, China.
To illustrate the potential of mesenchymal stem cell-derived exosomes (MSC-Exos) in mitigating septic lung injury by reducing the excessive formation of neutrophil extracellular traps (NETs), a mouse model of septic lung injury was induced through cecal ligation and puncture (CLP). The mice received intraperitoneal injections of MSC-Exos. Post injection, pathological alterations of the lung tissue were evaluated through HE staining, and the levels of inflammatory markers in each mouse group at various time points were assessed using ELISA kits.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and effectively repairing the heart following myocardial injuries remains a significant challenge. Research has increasingly shown that exosomes derived from mesenchymal stem cells (MSC-Exo) can ameliorate myocardial injuries and improve outcomes after such injuries. The therapeutic benefits of MSC-Exo are largely due to their capacity to deliver specific cargo, including microRNAs and proteins.
View Article and Find Full Text PDFJ Stomatol Oral Maxillofac Surg
January 2025
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077 Tamil Nadu, India. Electronic address:
Oral submucosal fibrosis is a highly malignant oral condition that necessitates the use of sophisticated therapeutic procedures. OSF is a multifactorial precancerous condition induced by areca nut chewing, deficiencies in vitamins and trace minerals, immunological aspects, and hereditary factors. Adipose tissue-derived mesenchymal stem cells possess the capability for multidirectional activation and are extensively distributed throughout the body.
View Article and Find Full Text PDFInt J Nanomedicine
December 2024
Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, 121000, People's Republic of China.
Introduction: Pulmonary hypertension (PH) is a progressive and life-threatening condition. Recent research has demonstrated that exosomes derived from mesenchymal stem cells (MSC) exhibit significant therapeutic potential in the treatment of PH. The composition of these exosomes is often substantially influenced by the characteristics of their parental cells.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Introduction: Sublingual immunotherapy (SLIT) is an effective and injection-free route for allergen-specific immunotherapy (AIT). Mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo) has been identified as a novel delivery platform with immunomodulatory capacities. In addition, targeting agents such as aptamers (Apt) have been extensively used for specific delivery approaches such as direct delivery of allergen formulations to dendritic cells (DC) to improve the efficacy of specific immunotherapy.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!