Angiopoietin-1 Modified Human Umbilical Cord Mesenchymal Stem Cell Therapy for Endotoxin-Induced Acute Lung Injury in Rats

• Published in: Yonsei medical journal 2017, 58(1), , pp.206-216
• Main Authors: Huang, Zhi Wei, Liu, Ning, Li, Dong, Zhang, Hai Yan, Wang, Ying, Liu, Yi, Zhang, Le Ling, Ju, Xiu Li
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - therapy; Angiopoietin-1 - genetics; Animals; Bronchoalveolar Lavage Fluid; Cytokines - metabolism; Endotoxins; Genetic Therapy; Interleukin-10 - metabolism; Interleukin-6 - metabolism; Leukocyte Count; Lipopolysaccharides; Lung - metabolism; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - metabolism; Neutrophils - metabolism; Original; Rats; Transforming Growth Factor beta1 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Umbilical Cord - cytology; 의학일반
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2017.58.1.206

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). 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. 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. 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.