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Xenogeneic and Allogeneic Mesenchymal Stem Cells Effectively Protect the Lung Against Ischemia-reperfusion Injury Through Downregulating the Inflammatory, Oxidative Stress, and Autophagic Signaling Pathways in Rat
- Source :
- Cell Transplantation, Cell Transplantation, Vol 29 (2020)
- Publication Year :
- 2020
-
Abstract
- This study tested the hypothesis that both allogenic adipose-derived mesenchymal stem cells (ADMSCs) and human inducible pluripotent stem cell-derived MSCs (iPS-MSCs) offered a comparable effect for protecting the lung against ischemia-reperfusion (IR) injury in rodent through downregulating the inflammatory, oxidative stress, and autophagic signaling pathways. Adult male Sprague–Dawley rats ( n = 32) were categorized into group 1 (sham-operated control), group 2 (IRI), group 3 [IRI + ADMSCs (1.0 × 106cells)/tail-vein administration at 0.5/18/36 h after IR], and group 4 [IRI + iPS-MSCs (1.0 × 106cells)/tail-vein administration at 0.5/18/36 h after IR], and lungs were harvested at 72 h after IR procedure. In vitro study demonstrated that protein expressions of three signaling pathways in inflammation (TLR4/MyD88/TAK1/IKK/I-κB/NF-κB/Cox-2/TNF-α/IL-1ß), mitochondrial damage/cell apoptosis (cytochrome C/cyclophilin D/DRP1/ASK1/APAF-1/mitochondrial-Bax/caspase3/8/9), and autophagy/cell death (ULK1/beclin-1/Atg5,7,12, ratio of LCB3-II/LC3B-I, p-AKT/m-TOR) were significantly higher in lung epithelial cells + 6h hypoxia as compared with the control, and those were significantly reversed by iPS-MSC treatment (all P < 0.001). Flow cytometric analysis revealed that percentages of the inflammatory cells in bronchioalveolar lavage fluid and circulation, and immune cells in circulation/spleen as well as circulatory early and late apoptotic cells were highest in group 2, lowest in group 1, and significantly higher in group 3 than in group 4 (all P < 0.0001). Microscopy showed the lung injury score and numbers of inflammatory cells and Western blot analysis showed the signaling pathways of inflammation, mitochondrial damage/cell apoptosis, autophagy, and oxidative stress exhibited an identical pattern of flow cytometric results among the four groups (all P < 0.0001). Both xenogeneic and allogenic MSCs protected the lung against IRI via suppressing the inflammatory, oxidative stress, and autophagic signaling.
- Subjects :
- Male
Programmed cell death
autophagy
Induced Pluripotent Stem Cells
Transplantation, Heterologous
Biomedical Engineering
lcsh:Medicine
Down-Regulation
Inflammation
Apoptosis
Lung injury
medicine.disease_cause
Mesenchymal Stem Cell Transplantation
Models, Biological
Rats, Sprague-Dawley
Immune system
medicine
Animals
Transplantation, Homologous
oxidative stress
Lung
Cell Proliferation
Transplantation
Cell Death
Chemistry
lcsh:R
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
medicine.disease
Mitochondria
Oxygen
Reperfusion Injury
Cancer research
Original Article
xenogeneic and allogenic MSCs
medicine.symptom
acute lung ischemia-reperfusion injury
Reperfusion injury
Oxidative stress
Biomarkers
DNA Damage
Signal Transduction
Subjects
Details
- ISSN :
- 15553892
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Cell transplantation
- Accession number :
- edsair.doi.dedup.....bf09ff7671740e1c82b359b552592f72