Details

Autor(en) / Beteiligte

• Wang, Shan
• Guo, Ling
• Ge, Jianfeng
• Yu, Lin
• Cai, Ting
• Tian, Ruiyun
• Jiang, Yuyang
• Zhao, Robert CH
• Wu, Yaojiong

Titel

Excess Integrins Cause Lung Entrapment of Mesenchymal Stem Cells

Ist Teil von

• Stem cells (Dayton, Ohio), 2015-11, Vol.33 (11), p.3315-3326

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Mesenchymal stem cells (MSCs) are largely entrapped in the lungs after intravenous delivery. The underlying mechanisms have been poorly understood. Flow cytometry and Western blot analysis showed that the expression levels of many integrins such as β1, α5, and αVβ3 in MSCs increased markedly upon cultured expansion in 2D monolayers, whose ligands fibronectin and vitronectin were detected on the surface of vascular endothelial cells in the lungs by immunostaining and flow cytometry. Blockade of integrin β1, integrin α5, or integrins αVβ3 with functional blocking antibodies significantly decreased the amount of MSCs entrapped in the lungs following intravenous infusion as determined by real‐time PCR and histological analysis; meanwhile, corresponding increases in the levels of circulating MSCs in the blood and MSCs homed to the ischemic myocardium and inflamed ear were found. Intriguingly, a short period of 3D spheroid culture of MSCs, which had been expanded for several passages in monolayers, substantially reduced the expression levels of many integrins and the number of MSCs entrapped in the lungs. Our results indicate that the excess expression and activation of integrins is a significant cause of lung entrapment of MSCs. Stem Cells 2015;33:3315–3326