Mesenchymal Stem Cell Microvesicles Restore Protein Permeability Across Primary Cultures of Injured Human Lung Microvascular Endothelial Cells

• DOI: 10.1002/sctm.17-0278
• Publication Date: 2018-05-08T09:41:39Z
• Authors: Shuling Hu; Jeonghyun Park; Airan Liu; JaeHoon Lee; Xiwen Zhang; Qi Hao; Jae-Woo Lee
• Keywords: Adherens junction; Exosome; Vascular permeability

Abstract Our previous study demonstrated that mesenchymal stem cell (MSC) microvesicles (MV) reduced lung inflammation, protein permeability, and pulmonary edema in endotoxin-induced acute injury mice. However, the underlying mechanisms for restoring permeability were not fully understood. In this current study, we hypothesized MSC MV would restore across injured human microvascular endothelial cells (HLMVEC) part through transfer of angiopoietin-1 (Ang1) mRNA to endothelium. A transwell coculture system was used effect on HLMVECs by cytomix, a mixture IL-1β, TNF-α, IFN-γ (50 ng/ml). result showed cytomix significantly increased FITC-dextran (70 kDa) over 24 hours. Administration MVs restored dose dependent manner, which associated with an increase Ang1 secretion This beneficial diminished when pretreated anti-CD44 antibody, suggesting internalization into HLMVEC required therapeutic effect. Fluorescent microscopy largely prevented reorganization cytoskeleton F-actin “actin stress fiber” location tight junction ZO-1 adherens VE-cadherin HLMVECs. siRNA pretreatment prior administration eliminated MV. summary, increasing HLMVEC.