期刊
HUMAN GENE THERAPY
卷 27, 期 8, 页码 621-630出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2016.003
关键词
-
资金
- National Natural Science Foundations of China [81201489, 81372093, 81571874, 81501705, 81300060, 81471843]
- Graduate Innovation Project in Jiangsu Province of China [KYZZ_0072]
Mesenchymal stem cells (MSCs) represent a promising approach for the treatment of acute respiratory distress syndrome (ARDS). However, their low efficiency in homing to injured lung tissue limits their therapeutic effect. Prostaglandin E-2 (PGE(2)) biosynthesis substantially enhances the inflammatory response of the tissue. Moreover, it also facilitates the migration of MSCs by activating the E-prostanoid 2 (EP2) receptor in vitro. Given these observations, it would seem reasonable that PGE(2) might act as a chemokine to promote the migration of MSCs through activation of the EP2 receptor. Herein, we confirmed that PGE(2) was significantly increased in lung tissue as a result of stimulation by LPS. In addition, we constructed a lentiviral vector carrying the EP2 gene, which was successfully transduced into MSCs (MSCs-EP2). Near-infrared imaging and immunofluorescence showed that compared with MSCs-GFP, MSCs-EP2 significantly enhanced MSC homing to injured lung tissue. Moreover, the diminished amounts of Evans blue in homogeneous lung parenchyma in vivo indicated, in comparison with MSCs-GFP, that MSCs-EP2 significantly decreased LPS-induced pulmonary vascular permeability. In addition, administration of MSCs-EP2 largely decreased the levels of interleukin-1 beta and tumor necrosis factor-alpha compared with that observed after administration of MSCs-GFP at both 24 and 72 hr. Our results suggested that treatment with MSCs-EP2 markedly enhanced MSC homing to damaged lung tissue and, in addition, improved both lung inflammation and permeability. Thus, MSCs and EP2 combination gene therapy could markedly facilitate MSC homing to areas of inflammation, representing a novel strategy for MSC-based gene therapy in inflammatory diseases.
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