Intravenous Transplantation of BMP2-Transduced Endothelial Progenitor Cells Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Rats

• Main Authors: Xiuru Yin, Zuodi Liang, Yue Yun, Ling Pei
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2015-04-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Endothelial progenitor cells; Bone morphogenetic protein; Lipopolysaccharide; Acute lung injury; Gene therapy
• Online Access: http://www.karger.com/Article/FullText/374020

Background/Aims: Acute lung injury (ALI) and its aggressive stage, acute respiratory distress syndrome (ARDS), are characterized by diffuse damage and increased permeability of the endothelial barrier, leading to alveolar infiltrates and interstitial edema. Enhancing endothelial integrity represents a novel therapeutic strategy for ALI/ARDS. Endothelial progenitor cells (EPCs) have been reported to participate in endothelial repair of ALI and also serve as a tool for gene therapy. Further, bone morphogenetic protein 2 (BMP2) is an essential signaling molecule that regulates the fate of different cell types. The aim of our study is to explore whether bone marrow-derived EPCs transduced with lentiviral-mediated BMP2 gene might benefit lipopolysaccharide (LPS)-induced ALI in a rat model. Methods: Rats were divided randomly into five groups. The sham group was given normal saline via the trachea and right jugular vein. The other four groups underwent intratracheal-LPS-induced ALI followed after 30 min by treatment with either normal saline, EPCs, EPCs transduced with empty lentiviral vector (EPCs-null), or EPCs transduced with BMP2 (EPCs-BMP2) via the right jugular vein. Results: We found that the lung injury score, oxygenation, and inflammatory response were significantly ameliorated in the three EPC-treated groups (EPCs, EPCs-null, and EPCs-BMP2). In addition, EPCs-BMP2 further improved endothelium repair and capillary permeability, causing markedly reduced wet-to-dry lung-weight ratio and BALF protein content, and increased levels of BMP2 protein, BMP2 mRNA, and eNOS protein in lung tissues. Conclusion: Transplantation of BMP2-transduced EPCs effectively attenuates edema and protein exudation compared with EPCs alone in LPS-induced ALI via enhanced expression of BMP2 and eNOS.