Angiopoietin-1 Modified Human Umbilical Cord Mesenchymal Stem Cell Therapy for Endotoxin-Induced Acute Lung Injury in Rats.
10.3349/ymj.2017.58.1.206
- Author:
Zhi Wei HUANG
1
;
Ning LIU
;
Dong LI
;
Hai Yan ZHANG
;
Ying WANG
;
Yi LIU
;
Le Ling ZHANG
;
Xiu Li JU
Author Information
1. Department of Hematology, The Qilu Childrens’ Hospital, Shandong University, Jinan, Shandong Province, P.R. China. lyssyl88@sina.com 2598260466@qq.com
- Publication Type:Original Article
- Keywords:
Angiopoietin-1;
human umbilical cord mesenchymal stem cell;
acute lung injury
- MeSH:
Acute Lung Injury/chemically induced/*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 Stromal Cells/metabolism;
Neutrophils/metabolism;
Rats;
Transforming Growth Factor beta1/metabolism;
Tumor Necrosis Factor-alpha/metabolism;
Umbilical Cord/*cytology
- From:Yonsei Medical Journal
2017;58(1):206-216
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
