Induced Pluripotent Stem Cells Attenuate Endothelial Leakage in Acute Lung Injury via Tissue Inhibitor of Metalloproteinases ‐1 to Reduce Focal Adhesion Kinase Activity

This study reports that induced pluripotent stem cells reduce the endothelial cell permeability by reversing lipopolysacchari de‐induced suppression of vascular endothelial cadherin in pulmonary endothelium. This study further suggested that induced pluripotent stem cells downregulate the expression of pFAK‐Tyr397 and Snail via tissue inhibitor of metalloproteinases‐1 in lipopolysaccharide‐induced acute lung injury . AbstractInduced pluripotent stem cells (iPSCs) can reduce the severity of endotoxin ‐induced acute lung injury (ALI). However, the interaction between iPSCs and vascular endothelium remains unclear. In this study, we investigated the effects of iPSCs in moderating pulmonary endothelial leakage in endotoxin‐induced ALI. Murine iPSCs were delivered intravenously to male C57BL/6 m ice (8–12 weeks old) 4 hours after intratracheal lipopolysaccharide (LPS) delivery. Histology, blood and bronchoalveolar lavage fluid (BALF) cytokine and junctional protein assays, and regulatory signaling pathway assays were performed 24 hours later. Human umbilical vein endothelial cells (HU VECs) were used as a model of junctional protein‐expressing cells and stimulated with LPS. Our results showed that iPSC treatment alleviated histological signs of ALI, protein leakage, and proinflammatory cytokines. iPSC therapy restored vascular endothelial cadherin (VE‐cadherin) expression in ALI mouse lungs. In HUVECs, human iPSCs (hiPSCs) restored disrupted VE‐cadherin exp...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research