Angiopoietin-1 Modified Human Umbilical Cord Mesenchymal Stem Cell Therapy for Endotoxin-Induced Acute Lung Injury in Rats
Open accessAbstract
PURPOSE: Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization and endothelial survival via inhibition of endothelial permeability and leukocyte- endothelium interactions. Hence, we hypothesized that treatment with umbilical cord mesenchymal stem cells (UCMSCs) carrying the Ang1 gene (UCMSCs-Ang1) might be a potential approach for acute lung injury (ALI) induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: UCMSCs with or without transfection with the human Ang1 gene were delivered intravenously into rats one hour after intra-abdominal instillation of LPS to induce ALI. After the rats were sacrificed at 6 hours, 24 hours, 48 hours, 8 days, and 15 days post-injection of LPS, the serum, the lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested for analysis, respectively. RESULTS: Administration of fluorescence microscope confirmed the increased presence of UCMSCs in the injured lungs. The evaluation of UCMSCs and UCMSCs-Ang1 actions revealed that Ang1 overexpression further decreased the levels of the pro-inflammatory cytokines TNF-α, TGF-β₁, and IL-6 and increased the expression of the anti-inflammatory cytokine IL-10 in the injured lungs. This synergy caused a substantial decrease in lung airspace inflammation and vascular leakage, characterized by significant reductions in wet/dry ratio, differential neutrophil counts, myeloperoxidase activity, and BALF. The rats treated by UCMSCs-Ang1 showed improved survival and lower ALI scores. CONCLUSION: UCMSCs-Ang1 could improve both systemic inflammation and alveolar permeability in ALI. UC-derived MSCs-based Ang1 gene therapy may be developed as a potential novel strategy for the treatment of ALI.
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Such VEGF upregulation may have important clinical implications since VEGF and Ang-1 have been shown to play pivotal roles in angiogenesis, alveolar development, and treatment of acute lung injury (ALI).
“Such upregulation may have important clinical implications since VEGF and Ang-1 have been shown to play pivotal roles in angiogenesis, alveolar development, and treatment of acute lung injury (ALI) [8, 57–60].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [59]
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- Authors
- Huang, Z.-W., Liu, N., Li, D., Zhang, H.-Y., Wang, Y., Liu, Y., Zhang, L.-L., & Ju, X.-L.
- Affiliations
- Department of Hematology, The Qilu Childrens' Hospital, Shandong University, Jinan, Shandong Province, P.R. China.
- Shandong University (CN)
- Qilu Hospital of Shandong University (CN)
- Corresponding author
- Zhang, Le-Ling
- Ju, Xiu-Li
- Venue
- Yonsei Medical Journal
- Publisher
- XMLink
- Published
- 2017
- Volume
- 58
- Issue
- 1
- Pages
- 206
- ISSN
- 0513-5796 (ISSN-L)
- 1976-2437
- PMC
- PMC5122639
- OpenAlex
- W2554479467
- Cited by
- 25
- References
- 21
- Citations by year
- 2024: 1 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 1
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Update notices
- Erratum (2022-05-19)
- Open access
- gold
- doi.org
- Licence
- Locations
- Yonsei Medical Journal (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Shandong Province (ZR2013HM001)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- angiopoietin-1, human umbilical cord mesenchymal stem cells, acute lung injury, lipopolysaccharide-induced lung injury, gene therapy, stem cell therapy, inflammatory cytokines, anti-inflammatory cytokines, vascular leakage, alveolitis, endothelial permeability, neutrophil infiltration
- MeSH terms
- Animals, Bronchoalveolar Lavage Fluid, Endotoxins, Leukocyte Count, Lipopolysaccharides, Lung, Male, Neutrophils, Tumor Necrosis Factor-alpha, Umbilical Cord, Genetic Therapy, Interleukin-6, Cytokines, Interleukin-10, Angiopoietin-1, Mesenchymal Stem Cell Transplantation, Rats, Transforming Growth Factor beta1, Acute Lung Injury, Mesenchymal Stem Cells
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